Dr.Armughan Riaz
M.B.B.S, Dip Card
Consultant Cardiologist


Thesis by dr Armughan Riaz

Comparison of desired levels of HDL and LDL in Acute Coronary Syndrome BY DR. ARMUGHAN  RIAZ, M.B.,B.S, Dip Card

Thesis by dr Armughan Riaz

Comparison of desired levels of HDL and LDL in Acute Coronary Syndrome
M.B.,B.S, Dip Card

Hypercholesterolemia is considered as major risk factor in ACS all over the world. A lot of research has been done concerning high LDL  in ACS. It has been an impression that low HDL is an important CAD risk factor along with high LDL in South Asians Communities. This study was conducted to validate this impression by observing and comparing the desired levels of HDL and LDL in ACS patients.

Purpose of Study: 
The scope for reduction in morbidity and mortality by early detection and treatment of hyperlipidemia has prompted us to conduct this study in our community in order to evaluate and compare levels of HDL and LDL in Acute coronary syndrome.

Material and Meathods:
The present clinical prospective Cohort study was carried out from dated 1st March,06 to 1st June 06 at Sialkot Medical Complex on 155 patients of ACS. Detailed History , physical examination and diagnostic tests were performed on every patient. Inclusion criteria was age between 25 and 75, both male and females and diagnostic criteria based on history , ECG findings and Cardiac Troponin T test results. Excluding criteria was Patient not giving consent, No specific ECG changes, Age < 25y and > 75y, End organ Damage, Congenital or valvular heart diseases, Cardiomyopathies
We see that there are 67% of patients have HDL level below 40mg/dl and 33% of patients had HDL level above 40mg/dl. Moreover, we have noticed that there are about 35% of patients who had isolated low HDL below 40mg/dl, thus considered as a single risk factor for ACS.
There are 84% of patients who have LDL level below 150 and 16% of patients had LDL above 150mg/dl. Only 5% of patients have been seen that had isolated high LDL greater than 150mg/dl. Thus only in 5% of patients, LDL was the single risk factor for ACS

We compared our study results with other related studies held in Pakistan and other South Asian Countries. Most of studies favor our hypothesis that HDL is also becoming one of most important emerging risk factor for ACS.

Along with high LDL, Low HDL is also considered as a major risk factor for Acute Coronary Syndrome. 67% of patients of ACS have HDL below desired level. While 35% of Patients have  Isolated Low HDL as the only risk factor . Only 5% of patients are seen in which isolated high LDL was considered as single risk factor. So in our conclusion, we will say decrease HDL level is probably more important as compared to high LDL in Asian patients of ACS, and it is often overlooked.Thus while controlling hyperlipidemia, not only LDL, but HDL should also be within normal limits.

Cardiovascular disease (CVD) is a major cause of morbidity and a leading contributor to mortality worldwide.18 Although CVD mortality has declined in economically developed countries, the emergence of a CVD epidemic has been observed in developing countries during recent decades 19. The absolute burden of CVD mortality is high in economically developing countries, and much of this burden in developing countries occurs in Pakistan.18 Over the next 20 years, CVD morbidity and mortality in China is projected to increase both in absolute number and as a proportion of total disease burden.20 The epidemic of CVD in economically developing countries has resulted, in large part, from the economic growth and associated sociodemographic change that has occurred over recent decades. During this period, the burden of illness from infectious disease has fallen, but changes in lifestyle and diet have led to an increase in life expectancy and a greatly increased burden of CVD and other chronic diseases.19,21,22.High blood cholesterol is one of the most important modifiable risk factors for CVD in western 23,24 as well as in Asian populations.

World Health Organization projected that, by 2020, at least 50% of all deaths due to CHD will occur in South Asian countries.15 There is compelling evidence that South Asians -- people who originate from India, Pakistan, Bangladesh and Sri Lanka – are at increased risk of CHD.16-17 Hypercholesterolemia is considered as major risk factor in ACS all over the world. Lot of work, studies and research has  been done concerning high LDL  in ACS. In our Community of South Asians, along with high LDL risk factor, low HDL is also getting more importance in patients of ACS.  Assuming that HDL levels are at lower values in ACS and LDL values are high in ACS,   we have conducted this study to observe and compare both high LDL and low HDL levels in ACS patients, and this study is hypothesized that in ACS , not only high LDL is a major risk factor but Low HDL is also considered as important risk factor in CHD patients. The Framingham Heart Study has been a strong proponent of   the Concept that a low serum HDL-cholesterol level is a major risk factor for CHD . 1,2,3,4,5,6,7. Framingham reports advise that the inverse association between HDL-cholesterol levels and CHD risk at least equals the positive association between CHD risk and serum LDL-cholesterol levels. Data from Framingham were Influential in the NCEP decision to classify a low HDL level as a major risk factor for CHD.8,9. 

LDL is currently the primary target of therapy for all patients and there is no special evidence based case for treatment at a lower threshold of LDL in south Asians. Control of the five major risk factors modeled by FINRISK reduces risk by 59 percent in south Asian men and 67 percent in south Asian women, with some subgroup heterogeneity, compared to 50% in European men and 48% in European women. Framingham and FINRISK models give similar results, mostly following expected patterns, but the SCORE model does not, probably reflecting its lack of inclusion of HDL and diabetes as risk factors, which may be more significant in south Asian populations. This suggests potential gains from controlling major established risk factors in south Asians, greater than in white Europeans. Over the past decade, researchers studying heart disease among South Asians have identified additional risk factors that may play a critical role in CAD among the South Asian population. These emerging risk factors include fibrinogen, insulin resistance and metabolic syndrome, low HDL, HDL2b, high triglycerides, small dense LDL, homocysteine.
Incidence of IHD is reported to be increasing sharply and substantial numbers of Pakistanis suffer their first heart attack at relatively younger ages of 40-50. Atherosclerosis of coronary arteries is the main cause of IHD in almost all cases, but the etiology and pathogenesis of atherosclerosis is not fully understood, however various observational epidemiological studies have shown that certain factors predispose to the development of atherosclerosis and resultant IHD. These factors are termed as risk factors. Major modifiable risk factors are hyperlipidemia, hypertension, smoking and diabetes Mellitus. In this study we have basically focused on hyperlipidemia in Acute Coronary Syndrome patients. 
In Pakistan such few studies have been conducted at tertiary care or teaching hospitals but at district level no data was ever planned to be collected and analyzed.. The scope for reduction in morbidity and mortality by early detection and treatment of hyperlipidemia has prompted us to conduct this study in our community.

Purpose of Study
Regarding Hyperlipidemia, In Pakistan such few studies have been conducted at tertiary care or teaching hospitals but at district level no data was ever planned to be collected and analyzed.. The scope for reduction in morbidity and mortality by early detection and treatment of hyperlipidemia has prompted us to conduct this study in our community. In our Community of South Asians, along with high LDL risk factor, Low HDL is also getting more importance in patients of ACS. That is why we are conducting this study to observe and compare both high LDL and low HDL levels in CHD, and this study is hypothesized that in ACS , not only high LDL is a major risk factor but Low HDL is also considered as emerging risk factor.

Materials and Methods
The present clinical prospective Cohort study was carried out from dated 1st March,06 to 1st June 06 at Sialkot Medical Complex. A total of about 155 patients (83 were males and 72 were female) of Acute Coronary syndrome were selected on basis of diagnostic criteria described below. Sialkot Medical Complex is equipped with bed sided and central cardiac monitoring, Echocardiography, ETT diagnostic tests. In every case detailed History, complete physical examination of the patient and relevant investigations were done and data was collected and recorded on special proforma.

Number of Patients:
155 Patients (83 males 72 Females) were enrolled in this study.

Inclusion Criteria:
• Age: Between 25 and 75 years
• Established diagnosis of ACS based on history, ECG changes and Cardiac Markers.
• Both Male and Female

Exclusion Criteria:
• Patient not giving consent.
• No specific ECG changes
• Age < 25y and > 75y.
• End organ Damage
• Congenital or valvular heart diseases.
• Cardiomyopathies

Proforma for Data Collection:
A data base of detailed demographic and clinical characteristics including Risk Factors was created prospectively. Data was collected by face to face , closed end questionnaire interview of the patient and attendants , directly by the author and a multivariate form was recorded at the same time.
The predicators for this project were consistent with current guideline and ethical recommendations. The focus was on evidence-based processes of care, according to the Performa attached and on the length and cause of the predictors with aggregate of central tendency.

We used following Proforma for data collection.

Proforma Data Collection Form

Serial # ------------  Ref # ---------------- Date --------------------------
Age:---------------Years          Sex: Male/Female
Address: Rural/Urban------------------------------------------------------
Socioeconomic Status:  P/M/U  (Poor/Middles class/Upper Class)

Diagnoses on bases of:
History: Chest Pain Yes/No, SOB Yes/No, Others Yes/No
ECG: ST segment:  Elevation/Depression
Twave inversion Yes/No
Q wave Yes/ No
Cardiac Markers: CK-Total CK-MB Cardiac-T

Weight :---------Kg      Height:-----------cm    BMI:-------------

Diet: Low Fat Diet / High Fat Diet

Physical Activity
Mild    100-20 Cal/hr,     Moderate   200-350Cal/hr    ,      Vigorous: 400-900cal/hr 

Drug History:
Thiazide Diuretics
Contraceptive pills

Alcohol Intake: Yes/No

Hypothyroidism: Yes/No

CRF: Yes/No

Hypertension:       mm of hg      Treatment: Regular/Irregular    BP:Cont/Uncont

Diabetes: Yes/No          Treatment: Regular/Irregular     BSL: Cont/Uncont

Smoking: Yes/No

Lipid Profile: Triglyc T.Chol HDL LDL mg/dl

Family History: Hypertension Y/N
                         Hypercholestrolemia        Y/N
Diabetes Y/N
Stroke Y/N
Sudden Cardiac death Y/N

Diagnostic Criteria:
• History, Symptoms and Sings: Typical history of retrosternal chest pain radiating to arm shoulder jaw or neck, associated with sweating or vomiting. Pain occurs at rest or during exertion. History of all risk factors  for IHD. All patients were examined to asses the presence of signs of Ischemic heart disease as transient MR, hypotension, diaphoresis, pulmonary edema or basal crepts.
• A twelve lead ECG was recorded in each patient with three channel ECG machine or single channel ECG machines (N.K.Cardiofax Gem FQW HO-2-140, NKE-A730 and AutoCardiner FCP-2155.) ECG was interpreted within 10 min of admission of each patient in supine position with a paper speed of 25mm/sec and 10mm/mv standardization. ECG was repeated at least once a day during admission.
Abnormal ST segment elevation defined as >/ o.2mv, 10msec after the J point, using PR segment as reference point , in 2 or more contiguous leads , in absence of LBBB or ventricular rhythm, ST segment depression was defined as > 0.05 mv, below the isoelectric base line, measured at the J-point and abnormal Q-wave as >0.03 sec in duration with Q/R ration > 1/3rd in > 2 contiguous leads.  T wave inversion was defined as T Symmetrical T wave inversion in contiguous group leads (>/=0.2mv).
• Cardiac Troponin T: was done on every patient of our study to rule out Non STSEMI. It was done by Cardiac Reader (Boehringer Mannheimgmbh). It was performed after 10 hrs of history of chest pain. Cardiac Troponins (cTn1 and cTnT) have a number of attractive features and have established acceptance as the biochemical markers of choice in the evaluation and diagnosis of patients of ACS. 25 In patients with UA/NSTEMI these markers provide both diagnostic as well as the prognostic information as there is a quantitative relationship between the magnitude of elevation of marker levels and the risk of an adverse outcome. 26

Aggregate measure of central tendency was calculated as below: -
MEAN VALUE; Mean = sum of all the observation values ÷ number of observations
MEDIAN VALUE; Median = the middle value of a set of data.
MINIMUM VALUE; The minimum value in an observed data.
MAXIMUM VALUE; The maximum value in an observed data.

Literature Review

Ischemic heart diseases have become a ubiquitous cause of morbidity and leading contributor to mortality in most South East countries.27.The health status and disease profile of human societies have historically been linked to the level of their economic development and social organizations with industrialization, the major causes of death and disability, in most advanced societies have shifted from predominance of nutritional deficiencies and infection disease, these classified as chronic diseases such as cardiovascular disease, diabetes and cancer. This shift has been termed epidemiological transition 28. At any given time the different countries of the World or even different regions with in a country are at different stages of epidemiological transition. This transition can occur not only between different disease categories (e.g. death from childhood diarrhea and malnutrition giving way to adult chronic diseases) but also within specify diseases category( e.g. rheumatic heart disease of long giving way to chronic coronary artery diseases of middle age or valve calcification and degeneration and heart failure of elderly) 29. The World Health Organization (WHO) stated in 2002 that in many regions some of the most formidable enemies of health are joining forces with the allies of poverty to impose a double burden of diseases, disability and premature death in many millions of people 30. This is what is happening in the South Asia, which houses one quarter of Global population and half of which lives below poverty line and has limited access to health care. The meager capita average budgetary expenditure on health ranging between US$ 11-20 31. For different countries of the region further highlights this challenge.

Burden of Cardiovascular diseases: 
According to WHO estimates, in 2003, 16.7 million people around the globe die of cardiovascular diseases each year. This is over 29% of all deaths globally32. By 2020 atherosclerotic disease will become the leading cause of both death and disability worldwide, with the number of fatalities projected to increase to more than 24 million a year by 2030 33.  This trend has given implication for countries in south Asia. Immigrant South Asians in the developed world have higher rates of cardiovascular diseases as compared to native people. Some studies suggest that the rate of diseases in the south Asians parallel those in the industrialized world. South Asians immigrants to united kingdom, south Africa, Singapore, and North America experience 1.5 times higher coronary heart disease mortality compared with indigenous population. 34,35,36. Located in the South Asia, Pakistan has a population of 140 million 37.  Surveys in Pakistan indicate very high prevalence rates of cardiovascular disease and risk factors with over 30% of the population over 45 years of age affected 37. In addition to High prevalence, cardiovascular disease appears to have a significantly younger onset and is known to be move aggressive in its presentation 38.

Temporal Trend:
The average life expectancy in India has increased from 41 years 1957 to 1961 to 61.4 in the years 1991 to 1996 and is projected to reach 72 years by 2030 which could lead to large increase in the cardiovascular disease prevalence 39. Death from cardiovascular disease in India increased from 1.17 millions in 1990 to 1.59 million in 2000 and are expected to rise to 2.03 million in 2010 40. A study done in 1994 found that prevalence of cardiovascular disease in Srilankan man aged 35-59 is 1.6% out of which 1.9% in higher  and 0.6% in lower socioeconomic groups in Urban population 48.
On the whole morbidity and mortality both are increasing in South Asian population with the period of time due to cardiovascular disease.

Risk Factors:
Smoking, Hypertension, and diabetes are strongly associated with cardiovascular disease among south Asians 41. In addition to traditional risk factors, there is increasing evidence that elevations from blood glucose even in non diabetic range increases cardiovascular disease risk amongst South Asians.
South Asians have elevated levels of LDL, which increases risk of atherosclerosis and thrombogenesis 42.  Recent studies have confirmed that South Asians have also higher levels of homocystein, fibrinogen and plasminogen activator inhibitor (PAI-1) and low HDL all of which could increase risk of thrombosis 43.

Lifestyle Changes:
Rural communities have lower risk factors than urban westernized population. With the rapid rural to urban migration in South Asia, prevalence of cardiovascular disease is increasing in urban population. Several cross-sectional surveys of urban and rural areas of different south Asian countries revealed that a higher prevalence of cardiovascular disease in urban population was associated with higher levels of body mass index, blood pressure, fasting blood lipids and diabetes.49,50,51.. A recent overview of prevalence surveys conducted over two decades in India reported a 9 fold increase in CHD in urban population compared with 2 fold increase in CHD rates among rural population. 52. Impaired fetal nutrition resulting in low birth weight is another rich factor which increases the prevalence of CHD in South Asians.53. This has also been implicated in the causation of metabolic syndrome, diabetes, and hypertension in later life. 54. This association has profound effect on South Asian Population where fetal and maternal malnutrition is common.

Hypertension causes 5 million premature deaths a year worldwide. About 15-37% of global adult population has hypertension. 55. In Asia a steep increases in stroke mortality has accompanied a rapid rise in prevalence of hypertension. Projected figures suggest that in India hypertension will increase from 16.3% to 19.45% between 1995 and 2025.56. According to National Health Survey of Pakistan conducted during 1990-94 prevalence of hypertension in adults was estimated to  be 23% and 18% in urban and rural areas respectively. 39. The unawareness rate in this survey has been reported at 70% which is amongst in the highest in the world. In Srilanka, reported rate of prevalence of hypertension is 17% in urban areas and 8 % in rural areas.57. while in Bangladesh Prevalence is 11.3%. 58. Factors such as delays in diagnosis, dietry habits and disparities in health system result in high prevalence of hypertension in south asians resulting in increase number of patients with target organ damage like heart failure, renal insufficiency and retinopathy.

An estimated one million people have type 2 diabetes globally and this figure is expected to be double by 2025. 55. South Asia has a higher number of people with diabetes than any other region with the estimates ranging from 19.4 million in 1995 to 32.7 million in 2000. 59. The International Diabetes Federation gives an estimate of 12% PREVALENCE IN Pakistan WITH A TOTAL OF 8.8 MILLIONPEOPLE WITH DIABETES IN 2000. THIS IS EXPECTED TO INCREASE TO 14.5 MILLION BY YEAR 2025. 59. In India, number of people with diabetes is expected to rise by 19.5% during 1995-2025 to reach 57.2% in 2025.60. The prevalence of diabetes in urban areas of Bangladesh is double that of rural area, 8% verses 4% and continuously rising in both. 61. In Srilanka, the diabetes prevalence is recorded as 8% in rural areas as compared to 12.5% in urban areas. 62. while in Nepal reported rates are 3% and 15% respectively. 63. Overall diabetes is associated with two fold increase in the risk of death from cardiovascular disease. Taking in view above data as the number of people with diabetes increases so the prevalence of Cardiovascular disease increases accordingly.

Metabolic Syndrome:
Metabolic syndrome is constellation of multiple factors like insulin resistance, abdominal obesity, dyslipidemia, and high blood pressure. It is estimated that worldwide people with metabolic syndrome are at increased risk, twice as likely to die from and three times as likely to have a heart attack or stroke compared to people without metabolic syndrome. 64. Asian have a lower BMI and waist circumference but can still have high insulin resistance, so the WHO has recently modified the BMI cutoff for obesity in Asian to greater than 23kg/m2 with waist circumference > 90cm for male and > 80cm for female.65. Several studies done on Soth Asians immigrants prove that they have hyperinsulinemia, raised triglyceride, low HDL cholesterol levels and abdominal obesity with high waist to hip ratio indicating condition of insulin resistance and high incidence of cardiovascular disease. 66-67.Recent studies have shown that metabolic syndrome is more prevalent in urban population of India, 68. Which is also true for Pakistani counterparts? 69. More population surveys are needed to profile south Asian propensity for metabolic syndrome. Very high prevalence of waist hip ratio among men (0.95) and women (0.85) and truncal obesity in both urban (men 39.1% and women 70.9%) as well as rural subjects (men 32.4% and women 42.3%) was reported from Delhi, India 70. In Srilanka 18.2% of population was labeled as leading a sendatary life 47. A 10% prevalence rate of obesity amongst rural males and 20% amongst urban females has been reported from Pakistan 39.
Epidemiological data reveal that in south Asia the prevalence of metabolic syndrome and type 2 diabetes is increasing markedly at lower level of BMI tan in western population. Interestingly, a great proportion of South Asians have a low HDL cholesterol and a genetic predisposition to insulin resistance, contributing to significantly high rate of metabolic syndrome and type 2 diabetes in this part of the world.

In India the prevalence of dyslipidemia in the industrial urban and rural populations in Delhi was reported as 30.9%, 36.8% and 16.3% respectively in men and 21.7%, 39.7% and 16.3% in women. 71.
Cholesterol levels are reported between 5.2-6.5mmol/L in 2.7.9% of rural and 26.5% of the urban Srilankan population.72. In Pakistan 12.6% of the population over 15 years of age is reported to have serum cholesterol level over 200mg/dl. 39. Numerous observational studies suggest that there is strong, graded and independent association between the dyslipidemia and risk of coronary heart disease. Asian population has increase risk of cardiovascular disease at lower level of cholesterol as compared to their western counterparts due to high genetic predisposition and increased level of physical inactivity.

Tobacco Trends;
Recent projections from WHO suggest that by the year 2020, Tobacco will become the largest single cause of death, accounting for 12.3% of global deaths.73. Tobacco use is highly prevalent in South Asia. Tobacco is smoked in several forms as Hukka, beeri and cigarette in addition to the practice of chewing tobacco in form of pan, niswar and naas absorbed through oral and nasal mucous membrane. In India alone, the tobacco attributable death toll will rise from 1.4% in 1990 to 13.35 in 2020. 73. The prevalence of smokeless chewable tobacco is very high in south Asia with over 10% of the population in Pakistan, 22% of men in India and 16% men and 21% women in Bangladesh.74. Although tobacco consumption is decreasing n developed countries but in developing countries its use in every form is increasing day by day and will be the major cause of morbidity and mortality in coming era.

Over the last few decades most countries in the world have experienced great transition in social structures, economic, politics, education and environment. This has resulted in shift from agricultural and rural societies to industrial and urban societies. South Asian region is also undergoing rapid urbanization, industrialization and major technological and life style changes, which has greatly affected the prevalence of cardiovascular diseases. Although the absence of well-established disease surveillance mechanism prevent precise estimation of the rate of prevalence of cardiovascular disease, the direction of change is clear the rate of prevalence is rising. More accurate estimation of disease burden, risk factors and time trends would helps to form better policies and guidelines for prevention and treatment.

Thus South Asian region is facing a period of challenge and opportunity as it embarks on the efforts to control the emerging epidemic of cardiovascular disease. National and regional efforts must be coordinated to recognize this epidemic and respond without delay.

Triglycerides and cholesterol are transported in the blood as Lipoproteins. Lipoproteins are named according to their density which depends on the percent of proteins in the particle. The higher the percent of protein, the higher the density.

From the least dense to most dense:

Structure and Composition of Lipoproteins:
All Lipoproteins consist of a hydrophilic shell and a hydrophobic core. The hydrophilic shell contains proteins, phospholipids and unestrified cholesterol. The hydrophobic core contains the neutral lipids, triacylglycerols and cholesterol esters which are highly insoluble in water.

Classes of Lipoproteins:
The four major classes of lipoproteins in human serum can be separated by electrophoresis on the bases of their size and charge or by centrifugation on the basis of their density.

Chylomicrons are the least dense of the lipoproteins and do not migrate in an electric field. They are formed in intestinal mucosa, and transport dietary triacylglycerol(TAG) and Cholesterol ester(CE) Chilomicrons are synthesized in endoplasmic reticulum of intestinal epithelial cells. The TAGs in chylomicrons are hydrolyzed by Lipoprotein lipase, an enzyme attached to the luminal surface of the vasculature of cardiac muscles, skeletal muscles and adipose tissues. Chilomicrons contain several apoprotins, including apo B48, Apo E and Apo C-11. Apo B48 is unique to chylomicrons, Apo C-11 activates lipoprotein lipase resulting in fatty acid release to heart, skeletal muscles and mammary glands. The presense of apo E facilitates the clearance of chylomicron remnants by the liver.

2: Very Low Density Lipoproteins:(VLDL)
VLDL are synthesized in the liver and transport TAG and CE. VLDLs are composed mainly of TAG, yet are more enriched in CE than are chylomicrons. VLDLs contain apo B100(required for uptake of LDL in peripheral tissues) Apo E (mediates uptake of remnants by the liver) and Apo c11 (activates lipoprotein lipase in capillary endothelium).When VLDL arrives in adipose capillaries, Apo C11 activates lipoprotein lipase. This releases fatty acids which are taken into the adipose and re-esterified into triglycerides. The glycerol returns to the liver. After VLDL release trigycerides, they become IDL. Intermediate density lipoproteins.

3:Intermediate Density Lipoproteins:IDL
IDLs also called (VLDL remnants) may be scavenged by the liver (Apo E) or may pick up cholesterol from HDL. As they acquire cholesterol they become LDL. The transfer of cholesterol ester from HDL to IDL is mediated by cholesterol ester transfer protein(CEPT)

4:Low Density Lipoproteins:LDL
LDL is generated from VLDLs and IDLs by the action of lipoproteins lipase, thus increasing the relative proportion of cholesterol esters in the neutral core. The major function of LDL is to transport cholesterol to the extra hepatic tissues where it is taken up by the receptor-mediated endocytosis. The LDL particle retains only Apo B100 and the uptake of LDL by cells is initiated by the interaction of Apo B100 with LDL receptors on the plasma membranes.

High Density Lipoproteins:(HDLS)
HDLs are synthesized by the liver and are approximately 50% protein. When the particle is secreted by the Liver, the core region is relatively empty. HDLs perform two major functions:

A: Circulating reservoir for apoproteins: 
Members of the apo A, Apo C and Apo E families can be transferred back and forth between other lipoproteins. Newly synthesized chylomicrons and VLDL particles obtain some of their apoproteins from the HDL reservoir following secretion.

b: Reverse Cholesterol Transport: 
HDLs are important in moving cholesterol from extra hepatic tissues to the liver. Elevated plasma levels of HDL are associated with decreased incidence of coronary atherosclerosis. Cholesterol is taken up from the surface of cells by HDL, esterified to cholesterol esters and ultimately returned to liver either by uptake of HDL particles by the liver or by the transfer of cholesterol esters to the VLDL and chylomicron remnants followed by remnant uptake. Two proteins play important roles in reverse cholesterol transport.

1_ Lecithin cholesterol acyl transferase(LCAT)
LCAT is a plasma enzyme that esterifies HDL cholesterol. The fatty acid used for esterfication comes from lecithin (Phosphatidylcholine). LCAT is activated by apo A-1 which is associated with HDL.

2-Cholestrol ester transfer protein:(ApoD)
Apo D is associated with HDL and facilitates the transfer of cholesterol esters to VLDL and chylomicrons remnants in exchange for triacylglycerol.

Cholesterol is a substance used to help digest fats, strengthen cell membranes and make hormones. When blood cholesterol reaches high levels, it can build up on artery walls, increasing the risk of blood clots, heart attack and stroke. There is strong evidence that lowering cholesterol concentrations reduces mortality from coronary heart disease (CHD).75,76 The West of Scotland Coronary Prevention Study (WOSCOPS) found that cholesterol-lowering drug therapy significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from non-cardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.77,78
Several guidelines have been drawn up giving different advice for managing hyperlipidaemia. The recent National Service Framework's guidelines on prevention of coronary heart disease in clinical practice suggest a cholesterol target of less than 5.0 mmol/l for both primary and secondary prevention.79
HDL-cholesterol is the fraction of cholesterol that removes cholesterol from the blood by carrying it to the liver where it is metabolised. HDL-cholesterol is inversely and independently associated with the risk of developing CHD,80,81 and low levels of HDL-cholesterol are also associated with a worse prognosis after myocardial infarction.82 A recent prospective study on middle-aged British men showed that higher levels of HDL-cholesterol were associated with a significant decrease in risk of nonfatal stroke.83 Modifiable risk factors such as smoking, alcohol consumption, raised body mass index and blood pressure are known to lower the concentrations of HDL-cholesterol. Attention is generally recommended for HDL-cholesterol concentrations below 1 mmol/l.
Coronary heart disease risk is influenced by elevated cholesterol, low density lipoprotein-c (LDL-C), triglycerides, hypertension cigarette smoking, Low HDL-C levels, family history, life habits, increased Lipoprotein (a), homo-cysteine 84, c-reactive protein, fibrinogen 85, and haematacrit 86.  A recent study 87 has shown that risk of death due to cardiovascular disease increases with raised levels of non-HDL-C. Non-HDL –C may also be a better parameter for cardiovascular risk assessment and as target for therapy 88.

Non-HDL-C is defined as the difference between total cholesterol (TC) and HDL-C and contains all known and potentially atherogenic lipid particles 88, including LDL-C, Lipoprotein (a), intermediate–density lipoprotein cholesterol and very low density lipoprotein cholesterol remnants, therefore a good and potential predictor of risk for cardiovascular diseases. Considering the importance of non-HDL-C, we carried out this cross-sectional study to evaluate the levels of non-HDL-C, a newly recognized risk factor, in patients of IHD.

Subclasses of HDL
With the use of segmented gradient gel electrophoresis (SGGE), a lab technique for separating and identifying blood components, lipoproteins can be sub classified to more accurately indicate cardiovascular risk. There are five subclasses of HDL — 2a, 2b, 3a, 3b, and 3c — but only 2b is cardio protective. HDL 2b is the most efficient form of HDL in reverse cholesterol transport, which vacuums the lipids from the endothelium.14
Patients with low total HDL levels often have low levels of HDL 2b. When levels of total HDL are between 40 and 60, cardio protective levels of HDL 2b are minimal. However, when levels of total HDL are greater than 60, levels of HDL 2b predominate and efficient reverse cholesterol transport takes place. This protects the coronary arteries from disease. The other subclasses of HDL are not capable of reverse cholesterol transport and therefore are not cardioprotective. Levels of HDL 2b can be increased by niacin supplements, but not by statin drugs (i.e., HMG CoA reductase inhibitors, such as simvastin or lovastatin).

Subclasses of LDL
Graph-K, LDL-S3GGE™Subclass Distribution.There are seven scientifically known LDL cholesterol subclasses, known as LDL I, IIa, IIb, IIIa, IIIb, IVa, and IVb. The subclasses of IIIa, IIIb, and IVb are made up of smaller, more dense particles (shaded) are more closely related to heart disease

With the use of SGGE, LDL has been divided into seven classes based on particle size. LDL IIIa and IIIb are the most commonly elevated forms of LDL. These particles are small enough to get between the endothelial cells and cause atheromatous disease. LDL IVa and IVb are also very small. These forms of LDL are associated with aggressive arterial plaques that are particularly vulnerable to ulceration and vascular occlusion. Nearly all patients whose LDL IVa and IVb levels are greater than 10% of total LDL will suffer a vascular event within months.14

LDL-S3GGE™Subclass Distribution.There are seven scientifically known LDL cholesterol subclasses, known as LDL I, IIa, IIb, IIIa, IIIb, IVa, and IVb. The subclasses of IIIa, IIIb, and IVb are made up of smaller, more dense particles (shaded) are more closely related to heart disease Graph K

It is characterized by intimal plaques called atheromas that produce into the lumen, weakened the underline media, and undergo a series of complications.1.
There are four major acquired risk factors that play an important role in process of atherosclerosis.1-Hyperlipidemia 2-Hypertension 3-Cigarette smoking 4-Diabetes.

Hyperlipidemia is virtually universally acknowledged to be a major risk factor for Atherosclerosis. Most of the evidence specifically implicates hypercholesterolemia but hypertriglyceridemia may also play a role. Large scale epidemiological statistics have demonstrated a significant co-relation between total plasma cholesterol and low density lipoprotein (LPL) level and the severity of AS as judged by mortality rate from IHD.
Hypertrigyceridemia as manifested by the elevated very Low density lipoprotein (VLDL) levels is also associated with some increased rate.
It is important at this point to emphasize the inverse relationship between symptomatic Atherosclerosis and the high density Lipoprotein (HDL) level. HDL participates in reverse transport of cholesterol and is believed to mobilize this lipid from cells and presumably from atherosclerotic plaques and transport it to liver for excretion in the bile. The higher the levels of HDL, the lower are the risk of IHD. Hence there is great interest in dietary levels of lowering serum LDL and raising serum HDL. Non dietary influences may also affect the level of blood lipids.

Hypertension is major risk factor for atherosclerosis at all ages and may well be more important than hypercholesterolemia after age 45. Men age 45 - 62 whose blood pressure exceeds 160/95mm Hg have more than fivefold greater risk of IHD than those with blood pressure of 140/90 mm of hg or lower. Both systolic and diastolic levels are important in increasing risk.

Smoking another important risk factor thought to account for the relatively recent increase in the incidence and severity of atherosclerosis in women. When one or more packs of cigarettes are smoked per day for several years, the death rate from IHD increases by up to 200%.

Diabetes induces hypercholesterolemia and a markedly increased predisposition to atherosclerosis.
Other Factors:
These include insufficient regular physical activity, competitive stressful life style with type A personality, obesity, the use of oral contraceptives, hyperuricemia, high carbohydrates intake and hyperhomocysteinemia.

Pathogenesis of Atherosclerosis:
Endothelial Injury:
Chronic or repeated endothelial injury is the corner stone of response to injury hypothesis. Circulating endotoxins, hypoxia, and products derived from cigarette smoke, viruses and specific endothelial toxins such as homocysteine are involved but thought to be much more likely are hemodynamic disturbances shear stress turbulent flow, adverse effects of hypercholesterolemia perhaps acting in concert. Shear stress and turbulent flow cause increased endothelial permeability and cell turnover, enhanced receptor mediated LDL endocytosis and increased endothelial adhesivity to leukocytes.

Hyperlipidemia contributes to atherosclerosis in many ways. Chronic hyperlipidemia particularly hypercholesterolemia may itself initiate endothelial dysfunction. With chronic hyperlipidemia, lipoproteins accumulate within the intima at sites of endothelial injury and dysfunction. Most importantly it provides the opportunity for modification of lipid in the arterial wall, largely by oxidative mechanisms, yielding modified LDL. Oxidative modification of LDL is currently thought to be a significant aspect of the atherogenic process. It is proposed that LDL in the microenvironment of interadharent monocytes and endotheial cells is exposed to free radicals generated by these activated cells. Oxidized LDL contributes to atherogenesis in the following ways.
It is readily ingested by macrophages through the scavenger receptor that is distinct from the LDL receptor. It is chemotactic for circulating monocytes. It increases monocytes adhesion, it inhibits the motility of macrophages already in lesions, and thus favoring the recruitment and retention of macrophages in the lesions. It stimulates the release of growth factors and cytokines. It is cytrotoxic to endothelial and SMCs, It is immunogenic.

Cellular events in Atherogensis:
A complex series of cellular events similar to those that occur in chronic inflammation are involved in process of atherosclerotic plaques. After some form of endothelial injury, monocytes adhere and migrate between endothelial cells to localize subendothelially. There they become transformed into macrophages and avidly engulf lipoproteins largely oxidized LDL to become foam cells. Oxidized LDL is chemotactic to monocytes and immobilizes macrophages at sites where it accumulates. Macrophages also proliferate in the intima. If the injury is denuding, platelets also adhere to the endothelium. early in the evolution of the lesion, some of the medial origin smooth muscle cells migrate and gather in the intima where they proliferate and some take-up lipids to also be transformed into foam cells, As long as the hypercholestrolemia persists monocytes adhesion sub endothelial migration of smooth muscle cells and accumulation of lipids within macrophages and smooth muscles cells continue, eventually yielding aggregates of foam cells in the intima, which are apparent microscopically as fatty streaks. 
Macrophages produce IL-1 and tumor necrosis factor (TNF) which increases adhesion of leukocytes, several chemokines generated by macrophages may recruit leukocytes into the plaque. Macrophages produce toxic oxygen species that also cause oxidation of the LDL in the lesions. Finally growth stimulators and growth inhibitors elaborated by macrophages may modulate the proliferation of smooth muscle cells and the deposition of extra cellular matrix in the lesions. T lymphocytes are also present in atheromas. Proliferation of smooth muscle cells about the focus of foam cells converts the fatty streak into a mature fibrofatty atheroma. Arterial smooth muscles can synthesize collagen elastin and glycoproteins. A number of growth factors have been implicated in the proliferation of smooth muscle cells, most importantly platelet derived growth factor PDGF, which is released from platelets adherent to the focus of endothelial injury but is also produced by macrophages endothelial cells and smooth muscles. Indeed the evolving atheroma has been likened to a chronic inflammatory reaction.
At this stage in atherogenesis, the intimal plaque represents a central aggregation of foam cells of macrophage and smooth muscle cells origin. With progression the cellular atheroma is modified by further deposition of collagen, elastins and proteoglycans. This connective tissue is particularly prominent on the intimal aspect where it produces the so called fibrous cap. Thus evolves the fully mature firofatty atheroma. Some atheromas undergo considerable cellular proliferation and connective tissue formation to yield fibrous plaques. Others retain a central core of lipid laden cells and fatty debris.
Thrombosis is a complication of late stage of atherosclerosis and organization of thrombi may contribute to plaque formation and their encroachment on the lumen.
A recent American Heart Association committee classified atherosclerotic lesions into six types beginning with the earliest fatty dots, through stages of fatty streaks, atheromas, and fibroatheromas, to the complicated lesions.
Figure 10-1 summarizes the major proposed mechanism of atherogenesis. This considers Atherosclerosis as a chronic inflammatory response of the vascular wall to the variety of initiating events that can occur early in life. Multiple mechanisms contribute to plaque formation and progression including endothelial dysfunction, monocyte adhesion and infltration, smooth muscle cell proliferation, extracellular matrix deposition, lipid accumulation and thrombosis. See fig 5, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 7, 8a, 8b, 9, 10, 11

Acute Coronary Syndrome

Acute coronary syndrome has evolved as a useful operational term to refer to any constellation of clinical symptoms that are compatible with acute myocardial ischemia. It encompasses acute myocardial infarction (ST-segment elevation and depression, Q wave and non Q wave) as well as unstable Angina. 89.

Unstable Angina / Non ST Segment elevation Myocardial Infarction constitutes a clinical syndrome that is usually but not always caused by atherosclerotic coronary artery disease(CAD) and is associated with increased risk of cardiac death and subsequent myocardial infarction.(MI)
The results of angiographic and angioscopic studies suggest that UA/NSTEMI often results from disruption of an atherosclerotic plaque and a subsequent cascade of pathological processes that decrease coronary blood flow. Most patients who die during UA/NSTEMI do so because of sudden death due to arrhythmias or the development of acute myocardial infarction (AMI). Unstable angina and NSTEMI are considered to be closely related conditions whose pathogenesis and clinical presentations are similar but of differing severity. The consideration is weather the ischemia is sever enough to cause some myocardial injury expressed by the detection of a biochemical cardiac marker, Troponin 90, which  becomes the basis for NSTEMI.
Among acute coronary ischemic syndromes (ACS), acute myocardial infarction (AMI) remains the leading single cause of death, with more than 1.5 million cases and more than 500,000 associated deaths per year….. Of the 5 million patients with a probable cardiac etiology, 20% will have an AMI, 16% will have unstable angina (UA), and 6% will die suddenly from a variety of causes.91 ACC/AHA Taskforce on practice guidelines 
The terms Ischemia, injury and infarction – the so called 3 I’s – have been used for decades to convey important concepts about coronary artery events.
Within seconds of the occlusion the first change to happen is Sub endocardial Ischemia. The ECG hallmark of Ischemia is ST- Segment depression.
If the ischaemia is prolonged for more than 20 to 30 minutes , injury changes begin to follow on the endocardial surface .These changes set up a current of injury that manifests on the ECG as ST- Segment elevation.

As the process evolves , the injured myocardial cells die(INFARCTION). Release of card iac markers begins after 20 to 30 minutes of total occlusion.
Infarction is the last step in the dying process of myocardial cells down stream from an acute coronary artery occlusion.Q wave development is the ECG hallmark.
Acute coronary syndrome is clinically defined as:
Spectrum (Fig 12) of conditions which includes
• Unstable angina 
• Non-ST segment elevation MI (non-STEMI) 
• ST elevation MI (STEMI) 
The syndrome is characterized by a clinical syndrome of acute ischaemic chest pain with either rest pain or a crescendo pattern of pain on minimal exertion, associated with ECG changes of ischaemia (ST elevation or depression or T inversion). STEMI is then distinguished from other forms of acute coronary syndrome (ACS) by the presence of persistent ST elevation. Patients with  often present in a similar manner. The distinction between non-STEMI and unstable angina is based on the presence or absence of a rise in cardiac enzymes or troponin.
In majority of cases syndrome occurs when an atherosclerotic plaque ruptures, fissures or ulcerates and precipitates thrombus formation. This results in sudden total or near-total arterial occlusion. Alternatively thrombus may break off from a ruptured plaque and occlude a downstream vessel. 
• systemic factors and inflammation also contribute to alterations in haemostatic and coagulation pathways and may play a part in the initiation of the intermittent thrombosis that is a characteristic of unstable angina. Inflammatory acute phase proteins, cytokines, chronic infections and catecholamine surges may enhance production of tissue factor, procoagulant activity or platelet hyperaggregability. 
• in the case of Q wave infarct results in a spreading area of necrosis that reaches epicardium in 4-6 h – full thickness infarct 
• in rare cases may be due to coronary artery occlusion by emboli, congenital abnormalities, coronary spasm and a wide variety of systemic (particularly inflammatory) diseases 
• initially infarcted muscle is softened leading to an increase in ventricular compliance but, as fibrosis takes place, compliance decreases 
• poor correlation between angiographic severity of coronary stenosis and chance of acute occlusion 
• Other causes of reduced myocardial blood flow include mechanical obstruction (e.g. air embolus), dynamic obstruction (e.g. vessel spasm), and inflammation or infection.

In the clinical assessment of chest pain, electrocardiography is an essential adjunct to the clinical history and physical examination (1)(FIG 13)
A rapid and accurate diagnosis in patients with acute myocardial infarction is vital, as expeditious reperfusion therapy can improve prognosis. The most frequently used electrocardiographic criterion for identifying acute myocardial infarction is ST segment elevation in two or more anatomically contiguous leads. The ST segment elevation associated with an evolving myocardial infarction is often readily identifiable. (FIG-14)
In the early stages of acute myocardial infarction the electrocardiogram may be normal or near normal; less than half of patients with acute myocardial infarction have clear diagnostic changes on their first trace. About 10% of patients with a proved acute myocardial infarction (on the basis of clinical history and enzymatic markers) fail to develop ST segment elevation or depression. In most cases, however, serial electrocardiograms show evolving changes that tend to follow well recognised patterns. 
Hyperacute T waves
The earliest signs of acute myocardial infarction are subtle and include increased T wave amplitude over the affected area. T waves become more prominent, symmetrical, and pointed ("hyperacute"). Hyperacute T waves are most evident in the anterior chest leads and are more readily visible when an old electrocardiogram is available for comparison. These changes in T waves are usually present for only five to 30 minutes after the onset of the infarction and are followed by ST segment changes. (FIG-14.1)

ST segment changes
In practice, ST segment elevation is often the earliest recognised sign of acute myocardial infarction and is usually evident within hours of the onset of symptoms. Initially the ST segment may straighten, with loss of the ST-T wave angle . Then the T wave becomes broad and the ST segment elevates, losing its normal concavity. As further elevation occurs, the ST segment tends to become convex upwards. The degree of ST segment elevation varies between subtle changes of <1 mm to gross elevation of >10 mm. 
Sometimes the QRS complex, the ST segment, and the T wave fuse to form a single monophasic deflection, called a giant R wave or "tombstone".FIG-15
Pathological Q waves
As the acute myocardial infarction evolves, changes to the QRS complex include loss of R wave height and the development of pathological Q waves. FIG 16

Both of these changes develop as a result of the loss of viable myocardium beneath the recording electrode, and the Q waves are the only firm electrocardiographic evidence of myocardial necrosis. Q waves may develop within one to two hours of the onset of symptoms of acute myocardial infarction, though often they take 12 hours and occasionally up to 24 hours to appear. The presence of pathological Q waves, however, does not necessarily indicate a completed infarct. If ST segment elevation and Q waves are evident on the electrocardiogram and the chest pain is of recent onset, the patient may still benefit from thrombolysis or direct intervention. 
When there is extensive myocardial infarction, Q waves act as a permanent marker of necrosis. With more localised infarction the scar tissue may contract during the healing process, reducing the size of the electrically inert area and causing the disappearance of the Q waves. 
Resolution of changes in ST segment and T waves
As the infarct evolves, the ST segment elevation diminishes and the T waves begin to invert. The ST segment elevation associated with an inferior myocardial infarction may take up to two weeks to resolve. ST segment elevation associated with anterior myocardial infarction may persist for even longer, and if a left ventricular aneurysm develops it may persist indefinitely. T wave inversion may also persist for many months and occasionally remains as a permanent sign of infarction. FIG - 17
Reciprocal ST segment depression
ST segment depression in leads remote from the site of an acute infarct is known as reciprocal change and is a highly sensitive indicator of acute myocardial infarction. Reciprocal changes are seen in up to 70% of inferior and 30% of anterior infarctions. 
Typically, the depressed ST segments tend to be horizontal or downsloping. The presence of reciprocal change is particularly useful when there is doubt about the clinical significance of ST segment elevation. FIG - 18
Reciprocal change strongly indicates acute infarction, with a sensitivity and positive predictive value of over 90%, though its absence does not rule out the diagnosis. FIG - 107
The pathogenesis of reciprocal change is uncertain. Reciprocal changes are most frequently seen when the infarct is large, and they may reflect an extension of the infarct or occur as a result of coexisting remote ischaemia. Alternatively, it may be a benign electrical phenomenon. The positive potentials that are recorded by electrodes facing the area of acute injury are projected as negative deflections in leads opposite the injured area, thus producing a "mirror image" change. Extensive reciprocal ST segment depression in remote regions often indicates widespread arterial disease and consequently carries a worse prognosis.

Localization of site of infarction
The distribution of changes recorded in acute myocardial infarction allows the area of infarction to be localised, thus indicating the site of arterial disease. Proximal arterial occlusions tend to produce the most widespread electrocardiographic abnormalities. The anterior and inferior aspects of the heart are the areas most commonly subject to infarction. Anteroseptal infarcts are highly specific indicators of disease of the left anterior descending artery. Isolated inferior infarcts changes in leads II, III, and aVF are usually associated with disease in the right coronary or distal circumflex artery. Disease in the proximal circumflex artery is often associated with a lateral infarct pattern that is, in leads I, aVL, V5, and V6. 
Anatomical relationship of leads 
Inferior wall Leads II, III, and aVF 
Anterior wall Leads V1 to V4 
Lateral wall Leads I, aVL, V5, and V6

Non-standard leads 
Right ventricle Right sided chest leads V1R to V6R 
Posterior wall Leads V7 to V9

Right ventricular infarction 
Right ventricular infarction is often overlooked, as standard 12 lead electrocardiography is not a particularly sensitive indicator of right ventricular damage. Right ventricular infarction is associated with 40% of inferior infarctions. It may also complicate some anterior infarctions but rarely occurs as an isolated phenomenon. On the standard 12 lead electrocardiogram right ventricular infarction is indicated by signs of inferior infarction, associated with ST segment elevation in lead V1. It is unusual for ST segment elevation in lead V1 to occur as an isolated phenomenon. 
Right sided chest leads are much more sensitive to the presence of right ventricular infarction. The most useful lead is lead V4R (an electrode is placed over the right fifth intercostal space in the mid-clavicular line). Lead V4R should be recorded as soon as possible in all patients with inferior infarction, as ST segment elevation in right ventricular infarction may be short lived.

Right ventricular infarction usually results from occlusion of the right coronary artery proximal to the right ventricular marginal branches, hence its association with inferior infarction. Less commonly, right ventricular infarction is associated with occlusion of the circumflex artery, and if this vessel is dominant there may be an associated inferolateral wall infarction. FIG 19, 20
Posterior myocardial infarction 
Posterior myocardial infarction refers to infarction of the posterobasal wall of the left ventricle. The diagnosis is often missed as the standard 12 lead electrocardiography does not include posterior leads. Early detection is important as expeditious thrombolytic treatment may improve the outcome for patients with posterior infarction. FIG 21
The changes of posterior myocardial infarction are seen indirectly in the anterior precordial leads. Leads V1 to V3 face the endocardial surface of the posterior wall of the left ventricle. As these leads record from the opposite side of the heart instead of directly over the infarct, the changes of posterior infarction are reversed in these leads. The R waves increase in size, becoming broader and dominant, and are associated with ST depression and upright T waves. This contrasts with the Q waves, ST segment elevation, and T wave inversion seen in acute anterior myocardial infarction. Ischaemia of the anterior wall of the left ventricle also produces ST segment depression in leads V1 to V3, and this must be differentiated from posterior myocardial infarction. The use of posterior leads V7 to V9 will show ST segment elevation in patients with posterior infarction. These additional leads therefore provide valuable information, and they help in identfying the patients who may benefit from urgent reperfusion therapy.

The grades of ischaemia.
In leads with usual Rs configuration (leads V1–V3):
grade I, tall symmetrical T wave without ST elevation;
grade II, ST elevation without distortion of the terminal portion of the QRS complex;
grade III, ST elevation with distortion of the terminal portion of the QRS (no S waves in leads V1–V3) (arrow).
In leads with usual q R configuration:
grade I, tall symmetrical T wave without ST elevation;
grade II, ST elevation with J point/R wave ratio <0.5;
grade III, ST elevation with J point/R wave ratio 0.5 (arrow).


In this study we have included the patients of Acute Coronary Syndrome ACS,
admitted to Sialkot Medical Complex, from dated 1st March,06 to 1st June 06. A
total of about 155 patients of Acute Coronary syndrome were selected on basis
of diagnostic criteria described earlier in this study.

Sex Distribution
Out of these 155 patients, 83 were males and 72 were female patients. Sex distribution is shown in graph (a)

Age of Patients
Age of patients ranges from 25 years to 75 years. Age distribution in 155 patients is shown in graph (b). 0.64% of patients have age between 20-30y, 4.50% pts have age between 30-40y, 20% of patients have age between 40-50y, 25% have age between 50-60y, 27% of pts have age between 60-70y and 13% have age between 70-80y.  52% of total patients belong to ages between 50-70y.

In 72 female patients 88% were house wives, 11% were working women. In 83 male patients 55% were manual workers, 10% were business men, 25% were retired and 5% were jobless.

Rural / Urban
Of about 155 patients, 57% belong to urban areas while 43% belong to rural areas.

We  have divided the patients in 2 groups, First group belong to patients with ST segment elevation in ECG, and another group with Non ST segment elevation. See diagnostic table (A) graph(d).

Out of 155 total patients of acute coronary syndrome, 49% (57 males and 32 Females) were diagnosed as acute myocardial infarction. Among these 49% patients of Acute MI, 31% were of Acute Anterior Wall MI, 50% were of Inferior wall MI, 10% were of Anterolateral wall MI and 7.7% were of extensive wall MI.
In another group we included patients with non st segment elevation. We have further divided this group in to two further subgroups bases on findings of Troponin T test positive or negative. 50.32% patients were placed in category of non st segment elevation group. In second group, Cardiac Troponin test was negative in 89% of patients and were diagnosed as Unstable Angina, while 10.25% of patients had cardiac T positive, and were diagnosed as Non QWMI.

Sex Distribution of 155 of ACS
Group I Pts of ACS will STEMI Male 57 49%
Female 32
group II pts of ACS will   None STEMI /UA Male 26 51%
Female 40

Signs and Symptoms:
The presenting symptoms and signs of 155 patients of Acute Coronary syndrome are tabulated at table ( b ) . Majority of patients had more than one symptoms, however if we see individually, we noticed that 77% of patients gave history of Typical chest pain, 19.35% of patients had shortness of breath, 66.45% had profuse sweating, 19.35% were complaining of vomiting , and 34% were having only feeling of nausea. 17.40% were telling about sinking of heart, and only 2.2% were having complaint of palpitation. 5% of patients had atypical presentation like abdominal pain, itching sensation, headache, syncope attacks, etc. Main associated symptoms with chest pain were dyspnea , sweating, vomiting and nausea, palpitations and sinking of heart. Overall 13% of patients presented with shock who had hypotension and clinical signs of hypoperfusion as pallor, cold clammy skin,  cyanosis, perspiration, confusion, irritability and oligurea. Bardycardia was present in 2% of patients. 7% of patients presented to us with history, symptoms and signs of left heart failure.
Base Line Symptoms in 155 Pts of ACS
Symptoms No lf Pts % of Pts
Typical Chest pain 120 77%
A typical Presentation 5 3.20%
Dyspnea SOB 30 19.35%
Sweating 103 66.45%
Vomiting 30 19.35%
Nausea 55 34.48%
Sinking of Heart 27 17.40%
Palpitation 4 2.58%

ECG Changes
In 77 patients of acute myocardial infarction, 97% of patients were having typical elevation of ST segment elevation of more than 0.2mv in two or more than two consecutive ECG leads. While only 3% of patients were showing hyper acute T waves which later showed elevation trend in ECGs, however there diagnosis was confirmed by echocardiography.
In 70 patients of Unstable Angina, 60% were having ST segment depression and another 40% have no specific changes in ECG. In 8 Patients of Non QWMI, all(100%) patients showed deep T wave inversion in lateral chest leads.

Cardiac Troponin T Findings
Cardiac Troponin T was performed on all patients of Acute Coronary syndrome, included in our study, to rule out patients of unstable angina and Non QWMI. Cardiac T was positive in 100% of patients of acute MI and 100% of NON QWMI. While patients with unstable Angina showed negative cardiac T findings. Table (c) shows findings of Cardiac T test in patients of ACS. 34% of patients had lower range values of cardiac T as 0.10-1.0ng, 18% of patients had strong values between 1-2ng and only 3.2% of patients had values greater than 2.

Distribution of Pts and Cardiac T Value
No of PTS % of pts Cardiac T Value ng
53 34% 0.10-1.00
28 18% 1.00-2.00
5 3.20% >2.00

Obesity (BMI Findings)
In general, Out of 155 patients, 57.40% of patients had BMI > 25 and 43% of patients had BMI less than 25. Among patients that showed BMI greater than 25, 38% were females and 19.35% were males. See BMI findings and distribution of greater BMI among males and females in graphs (d ) and (e)
If we see individually, 9% of patients were having BMI less than 20, 32% of patients had BMI between  20 -25, 30% of patients had BMI between 25-30, 17% of patients showed BMI between 30-35, 6.4% of patients showed BMI between 35-40 and only 3.2% of patients had BMI greater than 40.

In our study, 57.40% of patients had BMI greater than 25, when we compare other risk factors in these obese patients we see that All the parameters except serum HDL level showed significant increase in obese persons while HDL level was significantly decreased. 43% of these obese persons had diabetes, 17% had hypertension alone or with diabetes. 27% showed hyperlipidemia, with greater LDL > 150 and HDL level below 40mg/dl. ( Graph e shows distribution of BMI>25 in males & females )

Diet History:
67% of both males and females were taking high fat diet including meat chicken butter, cheese. While 33% of patients were taking low fat diet including vegetables, salad, plenty of water intake daily.

Physical Activity:
35% of patients were having mild physical activity, 61% were having moderate physical activity and 2% were having vigorous physical activity. Specially those who live in rural areas show more physical activity rather than those who live urban areas.

Risk Factors
A: Hypertension:
Comparison of risk factors of acute coronary syndrome in both males and females patients is shown in graph (F). As a whole, it was noted that out of 155 patients of ACS , 56% were hypertensive, (36% males, 20% females), out of which only 6% were taking regular medication and their Blood pressure was under controlled limits, and 50% of patients of hypertension were not taking any medication for their high blood pressure and their blood pressure was found to be in high ranges.

B: Smoking
36% of patients were found to be chronic smokers. Usually smoking 1 or more packs of cigarettes daily. 2% of females were also smokers, however those were taking Huqqa smoke. 34% of males patients of ACS were chronic smokers.

C: Diabetes:
We have noticed that 60% of patients were diabetics, among which 53% were on irregular medication or not taking any medicine at all, their BSR and fasting sugar levels were found to be in higher limits. Only 7% of patients of ACS were taking regular medication and their BSR and fasting blood glucose was within normal range.

D: Hyperlipidemia
Discussed below in detail
E: Alcohol:
In our study only 1.30% of ACS  patients were taking alcohol.
F: Hypothyroidism:
2% of patients were known patients of hypothyroidism and were taking regular medication. Their T3, T4, TSH were found to be within normal limits.

Drug History:
We noticed that 6% of patients were taking thiazide diuretics along with other antihypertensive drugs. 0.60% of patients were taking corticosteroids as treatment of bronchial asthma. 1.00% of female patients were taking contraceptive pills. Drugs are tabulated in table (d)

Drugs Taking by pts
Name of Drug No of pts
Thiazide 9
Corticosteroids 1
Contraceptives 3
Others 0

Table (D)
Family History:
In our study , we have noticed that as a whole 67% of patients of ACS gave positive family history of hypertension , Hypercholesterolemia,  Diabetes, Ischemic heart diseases, Stroke and sudden death. If we see individually, 43% of patients gave positive family history of hypertension and diabetes alone.

Lipid Profile
Triglyceride level distribution in 155 patients is shown in graph (G) and Table (E).We noticed in our study, that there are  about 25.80% (30males, 10 Females) who have triglyceride level between 0-100mg/dl. 36.12% (27males, 25 females) have triglyceride level between 100-200mg/dl. 20% (11males, 20 females) have triglycerides between 200-300mg/dl. 18% of pts (20males, 8 females) have triglyceride level greater than 300mg/dl.
Overall we see that there are 61% of patients who have triglyceride level less than 200mg/dl, and 38% of patients of ACS have triglyceride level greater than 200mg/dl.
 Level of Triglycerides 
Table E
Level of Triglycerides Number of Patients
0--100 40
100--200 56
200--300 31
>300 28

Total Cholesterol:
Cholesterol level distribution in patients of ACS is shown in graph (h) and table (F). 57% of patients (30males and 59 Females) had cholesterol level less than 200mg/dl. 34% of patients of ACS (20 males, 33 Females) have cholesterol level between 200-300mg/dl. 8.3% of patients of ACS (6 males , 7 females) have cholesterol level above 300mg/dl. Overall we see that there are 57% of patients of ACS who had cholesterol level less than 200mg/dl and 42% of patients had cholesterol level greater than 200mg/dl.

  Total Cholesterol Level  
Cholestrol Level No of pts % of pts
<200 89 57%
200 -- 300 53 34%
>300 13 8.30%

HDL Level:
HDL level distribution in patients of ACS is shown in graph (i) and Table (g). We noticed in our study that there are 4% (3males, 3 females)of patients of ACS who had HDL level between 10-20mg/dl. 23% (24males, 12 females) of patients of ACS who had HDL level between 20-30mg/dl. 40% (40males , 22 females)of patients of ACS who had HDL level between 30-40mg/dl. 30% of patients (13 males, 17 females) had HDL between 40-50mg/dl. Only 2% of patients (2males, 2 females) had HDL  level greater than 50mg/dl. Overall, we see that there are 67% of patients have HDL level below 40 and 33% of patients had HDL level above 40mg/dl. Moreover, we have noticed that there are about 35% of patients who had isolated low HDL below 40mg/dl, thus considered as a single risk factor for ACS. Sex wise comparison showed that females had higher HDL level than males. In our study , 13% of females had HDL> than 40mg/dl.and only 9% of males had HDL>40mg/dl. Similarly, we see that out of 67% of patients who had HDL below 40mg/dl, 80% of these were above 50 years.

Table G

 HDL Level in ACS pts 
HDL mg(d) No of pts % of pts
10  --  20 6 4%
20  --  30 36 23%
30  --  40 62 40%
40  --  50 47 30%
> 50 4 2%

Distribution of HDL Levels in Males and Females

LDL Levels:
LDL level distribution in patients of ACS is shown in graph (j), Table (h). 40% (30males,32 females) had LDL level below 100mg/dl. 44.50% (39 males, 30 females) had LDL between 100-150mg/dl. And 15.48% of patients ( 17 males 7 females) had LDL levels greater than 150mg/dl. As a whole, we see that there are 84% of patients which have LDL level below 150 and 16% of patients had LDL above 150mg/dl. Only 5% of patients have been seen that had isolated high LDL greater than 150mg/dl. Thus only in 5% of patients, LDL was the single risk factor for ACS. We see that out of 16% of patients who had LDL above 150mg/dl, 70% of these were above 50 years.

 LDL Level in ACS pts 
LDL Level No of pts % of pts
<100 62 40%
100  --  150 69 44.50%
>150 24 15.48%

Table H

Over all view of Triglycerides,Total cholestrol , HDL ad CDL among pts of ACS
Triglyerides Total Cholestrol HDL LDL
<200 = 62% <200 = 57% <40 = 67% <100 = 84%
>200 = 38 % >200 = 42% >40 = 33% >100 = 16%

It has been mentioned that IHD is on the increase in the developing countries 1, 2, 3 and more so in Pakistan 4,5,6,7. In early 1950s and 1960s, sporadic reports from different hospitals of Pakistan showed a gradual increase in the admission of ACS patients.  There are many risk factors for acute coronary syndrome. e.g, Hypertension,  smoking, Hypercholesterolemia, Diabetes etc. In our present study we focus on comparison of Low HDL and High LDL in ACS patients and our main objective is to report the association of  Lower  levels of   HDL and high Levels of LDL in ACS.
In present study we have seen that there are 67% of patients of ACS (Both Males and Females) have HDL level below 40 and only 33% of patients have HDL level above 40. However, if we see levels of LDL, there are 84% of patients(Both male and female) who have LDL below 150mg/dl and only 15% of patients have LDL above 150mg/dl. Lower Levels of HDL is getting more importance in South East countries than High Levels of LDL in patients of acute Coronary patients.
Different studies have been conducted in Pakistan and western countries go in favor of our study results. In one Pakistani study, High prevalence of hypertriglyceridemia and low HDL-cholesterol (which constitute a component of metabolic syndrome) in Pakistani AMI patients is suggestive that these two lipid abnormalities could be playing a major role in the development of atherosclerosis in Pakistani population.92
High levels of triglycerides and low levels of HDL-cholesterol are the most prominent abnormalities in Pakistani adults working in tertiary health care centers.93
Another study of Pakistan, which favors our hypothesis, High prevalence of hypertriglyceridemia and low HDL-cholesterol (which constitute a component  of metabolic syndrome) in Pakistani AMI patients is suggestive that these two lipid abnormalities could be playing a major role in the development of atherosclerosis in Pakistani population 94
The prevalence of low HDL-cholesterol (<1 mmol/l) was relatively high among South Asian groups, in particular among Indian women (risk ratio 1.61) and Pakistani and Bangladeshi men (risk ratios 1.67, 2.68) and women (risk ratios 2.39, 3.67). Black Caribbean’s had a relatively low prevalence of low HDL-cholesterol (risk ratio 0.61 for men, 0.57 for women). 95
In one study, Castelli WP et al. were able to show an inverse association of high HDL-C and low coronary risk was as statically as strong as the direct association of high LDL-C and high coronary risk in a cohort of men and women age 40–82 followed for 12 years who were free from CAD at study entry. At any level of cholesterol low HDL-C increases the rate of CHD.96 The NCEP ATP III guidelines clearly defines a level < 40 mg/dl as an independent risk factor for CHD 97
In another study, Michael Miller has stated: "Low HDL-C is the most common lipoprotein abnormality in patients with CHD and is predictive of CHD events, even when total cholesterol levels are normal" 98 Jordanian patients with CAD have higher cholesterol, LDL-C, Triglyceride and lower HDL-C levels than the control group which comes in accordance of other studies. Hyperlipidemia remains the strongest risk factor for CAD. 99
In one Chinese study, risk factors for ACS were studied; HDL-C and hypertension were independent predictors of CAD. Prevention of CAD, the goals should be to reduce LDL-C concentration to below 100 mg/dl and the TC concentration to below 160 mg/dl. However, other risk factors like Low HDL should also be considered 100
In another study, AMI occurrence and CHD death in normal HDL-C group were lower than those in the low HDL-C group by 40% and 53%; and those in the high HDL-C group were lower than in the normal group by 56% and 50%, respectively.The results demonstrated that the protective effect of HDL against coronary artery disease is more prominent in people with low lipid level. Low HDL is an important independent risk factor for AMI attacks and CHD death in the elderly; high HDL has significant protective effect against coronary artery disease. 101
In our study we have seen that there are about 35% of patients who has isolated lower HDL (Less than 40). In 1977 the Tromso Heart Study demonstrated that CAD patients have HDL-C levels 35% lower than controls and those patients with low HDL-C are three times more likely to develop CAD than those with elevated LDL-C. These early views certainly support the concept that an isolated low HDL-C is a common antecedent of clinical CHD, as well as being important in accelerating the progression of atherosclerosis.102
In another study, low HDL-C levels in association with desirable LDL-C levels are present in more than one fifth of male patients with CHD.Clinical trials focusing on this large group are urgently needed to determine whether efforts to raise HDL-C levels result in reduced cardiac morbidity and/or mortality. If we compare it with our study, isolated lower HDL is present in 28% males and 9% females with ACS.103
One more Study shows that CAD prevalence at HDL levels of 30 mg/dL (0.78 mmol/dL) is more than double that at 60 mg/dL, and high levels of LDL or low levels of HDL are independently associated with increased CAD risk. One must determine, therefore, whether elevated TC levels are due to increased LDL or HDL.104
In our study there are 57% of patients who are over weight and have BMI greater than 25.All the parameters except serum HDL level showed significant increase in obese persons while HDL level was significantly decreased. 
In another study held in Allama Iqbal medical Colledge, Lahore, Pakistan, Lipid levels of obese IHD patients were observed, It had been seen that obese patients of IHD were having greater incidence of high LDL, Hypercholesterolemia, hypertriglyceridemia while HDL was significantly lower in obese patients. 105 It has been estimated that risk of myocardial infarction is 35% to 55% less in adults and normal weight as compared to obese adults.106. However, the influence of obesity on cardiovascular risk begins before adulthood and overweight during adolescence is associated with an increased risk of coronary heart disease in male and female subjects107. In our study there are 57% of patients who are over weight and have BMI greater than 25.
In our study Age wise comparison revealed that level of total cholesterol; triglyceride and LDL-C were elevating while the level of HDL-C were decreasing with the age in patients of ACS. Sex wise comparison showed that females had higher HDL-C level than males.
Department of Chemistry, Gomal University, Dera Ismail Khan, NWFP, Pakistan.Lipid profile in cardiac patients (myocardial infarction, angina pectoris, coronary heart disease, ischaemic heart disease), diabetic patients and normal humans was investigated. Total serum cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, blood glucose, calcium, potassium and sodium were determined, employing established methods and procedures. Higher level of total cholesterol, LDL-C and triglyceride were found in both cardiac and diabetic patients, however, cardiac patients had much lower level of HDL-C as compared to normal humans. Age wise comparison revealed that level of total cholesterol; triglyceride and LDL-C were elevating while the level of HDL-C was decreasing with the age in cardiac and diabetic patients. Sex wise comparison showed that females had higher than males.108 
In one study of north Indians, Younger patients have a more atherogenic lipid profile than the older subgroup with coronary artery disease, and smoking and a family history of premature coronary artery disease are the most common associated risk factors.109. In another Chinese study, Serum HDL-C levels were significantly lower in both CHD and CVD patients than in healthy subjects of comparable sex and age 110. In another study, it has been noted that high TC and LDL-C levels are correlated with a high CHD risk even in people over 80. For elderly patients with clinical CHD and an aggregation of CHD risk factors, cholesterol-lowering therapy might be considered if the general health of the patient makes this permissible.111. A study of the lipid profile of 200 normal Nigerian subjects (Group A) shows a steady increase in the total cholesterol and triglyceride values with increasing age in both sexes, while the high density lipoprotein (HDL) cholesterol and percent HDL cholesterol values show a steady decrease with increasing age in both sexes.112
In our study we have seen that patients with Low HDL and high LDL have also more incidence of other risk factors like Hypertension, Smoking and Diabetes. Out of 155 patients of ACS,56% (87) were Hypertensive, 36% 56 patients were smokers and 60% 93 patients were diabetics.
In one Canadian Study, among men or women with low HDL-C and high triglyceride levels, smoking, diabetes, sedentariness, hypertension and obesity were much more prevalent than among those at low risk with high HDL-C and low triglyceride levels.113. Patients with elevated LDL-C, low HDL-C, and elevated triglycerides were more likely than patients with isolated LDL-C elevation to have other characteristics of the metabolic syndrome, had increased risk for CHD events on placebo,10. Similarly In Tehran Lipid and Glucose Study low HDL-C levels (< 35 mg/dL) were observed in 31% of the men and 13% of the women, Obese subjects (BMI > or = 30 kg/m2) had a significantly lower HDL-C level than the normal subjects (42 +/- 11 vs 44 +/- 11 mg/dL: ). Smokers had a significantly lower HDL-C level than non-smokers (38 +/- 10 vs 43 +/- 11 mg/dL; p < 0.001) and a low HDL-C level was twice as common (36.4 vs 18.2%).Smokers had a significantly lower HDL-C level than non-smokers (38 +/- 10 vs 43 +/- 11 mg/dL; p < 0.001) Mean serum HDL-C was significantly lower in hypertriglyceridemic than those with normal triglycerides levels (men: 4 +/- 8 vs 40 +/- 9 mg/dL, p < 0.001; women: 40 +/- 10 vs 47 +/- 11 mg/dL, Mean HDL-C levels were similar in subjects with different degrees of physical activity, as well as between diabetics and non-diabetics and hypertensive and normotensive subjects. Apart from age and sex which are constitutional, and unmodifiable variables, the determinants of HDL-C level (hypertriglyceria, obesity, truncal obesity, cigarette smoking, and passive smoking) can be used in community CAD prevention programmes.11
In our study, 38% of patients have Triglycerides greater than 200, 42% of patients have cholesterol greater than 200, 15% of patients have LDL greater than 150. In one study held in Ayub Med Coll Abbottabad Non-HDL-C contains all known potentially atherogenic lipid particles including LDL-C, intermediate density lipoproteins and very low density lipoproteins cholesterol remnants. Results of this study suggest its possible involvement in IHD. Non-HDL-C is an emerging coronary risk factor. It is a cost effective screening test that may be included in coronary risk profile.12
In our study we have noted another important finding that risk factors specially hypertension, Diabetes, central obesity and hyperlipidemia were more common in women as compared to men. While smoking was more common in men. In another study held in Pakistan, The proportion of hypertension (20.2% vs 17.4%, p = 0.003), hyperlipidemia (14.6% vs 10.1%, p < 0.001), and central obesity (42.4% vs 14.7%, p < 0.001) were also significantly greater in women than in men. Not surprisingly, current cigarette smoking was significantly less common in women than men (3.4% vs 28.5%, p < 0.001) whereas there was no significant difference between the sexes in high intake of meat, diabetes and proteinuria. Daily intake of ghee/butter was significantly higher in women compared to men 13. Unlike data from many developed countries where there is an association between low socioeconomic status and high risk for the metabolic clustering of risk factors, this study found that subjects belonging to mid and high socioeconomic strata had higher odds of coexistence of risk factors. It probably reflects greater physical activity on the part of lower SES individuals in Pakistan (for example in agricultural work) compared to similar individuals in the United States and other industrialized nations.


A: Along with high LDL, Low HDL is also considered as a major risk factor for Acute Coronary Syndrome.

B: 67% of patients of ACS have HDL below desired level. While 35% of Patients have  Isolated Low HDL as the only risk factor . Only 5% of patients are seen in which isolated high LDL was considered as single risk factor. So in our conclusion, we will say decrease HDL level is probably more important as compared to high LDL in Asian patients of ACS, and it is often overlooked.Thus while controlling hyperlipidemia, not only LDL, but HDL should also be within normal limits.

C: All the parameters except serum HDL level showed significant increase in obese persons while HDL level was significantly decreased.

D: In our study Age wise comparison revealed that level of total cholesterol; triglyceride and LDL-C were elevating while the level of HDL-C were decreasing with the age in patients of ACS. Sex wise comparison showed that females had higher HDL-C level than males.

E: Patients with Low HDL and high LDL has also more incidence of other risk factors like Hypertension, Smoking and Diabetes.

1 Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High-density lipoprotein as a protective factor against coronary heart disease: the Framingham Study. Am J Med.. 1977;62:707–714.

2 Castelli WP, Doyle JT, Gordon T, Hames CG, Hjortland MC, Hulley SB, Kagan A, Zukel WJ. HDL cholesterol and other lipids in coronary heart disease: the Cooperative Lipoprotein Phenotyping Study. Circulation.. 1977;55:767–772.

3 Abbott RD, Wilson PW, Kannel WB, Castelli WP. High density lipoprotein cholesterol, total cholesterol screening, and myocardial infarction: the Framingham Study. Arteriosclerosis. 1988;8:207–211.

4 Wilson PW, Abbott RD, Castelli WP. High density lipoprotein cholesterol and mortality: the Framingham Heart Study. Arteriosclerosis. 1988;8:737–741.

5 Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, Jacobs DR Jr, Bangdiwala S, Tyroler HA. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation. 1989;79:8–15.

6 Schaefer EJ, Moussa PB, Wilson PW, McGee D, Dallal G, Castelli WP. Plasma lipoproteins in healthy octogenarians: lack of reduced high density lipoprotein cholesterol levels: results from the Framingham Heart Study. Metabolism. 1989;38:293–296.

7 Wilson PW. High-density lipoprotein, low-density lipoprotein, and coronary artery disease. Am J Cardiol. 1990;66:7A–10A.

8 Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA.. 1993;269:3015–3023.

9 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation.. 1994;89:1329–1445.

10- Ballantyne CM, Olsson AG, Cook TJ, Mercuri MF, Pedersen TR, Kjekshus J. ,  Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S.Circulation. 2001 Dec 18;104(25):3046-51.

11- Azizi F, Raiszadeh F, Salehi P, Rahmani M, Emami H, Ghanbarian A, Hajipour R. Related Articles, Links  Determinants of serum HDL-C level in a Tehran urban population: the Tehran Lipid and Glucose Study.Nutr Metab Cardiovasc Dis. 2002 Apr;12(2):80-9. PMID: 12189907  

12- Tauheed S, Shoaib S, ul Haque MN, Levels of non-high density lipoprotein cholesterol (non-HDL-C) in patients with ischaemic heart disease.J Ayub Med Coll Abbottabad. 2003 Jan-Mar;15(1):33-4. PMID: 12870314

13- Jafar, TH. Women in Pakistan have a greater burden of clinical cardiovascular risk factors than men. Int. J Cardiol;106 (2006):348-354

14-Pagana KD, Pagana TJ. Mosby’s Manual of Diagnostic and Laboratory Tests. 3rd ed. St. Louis, MO: Mosby/Elsevier; 2006.

15-Lopez AD. Assessing the burden of mortality from cardiovascular diseases. World Health Stat Q 1993;46:91-6.

16 Jha P, Enas EA, Yusuf S. Coronary artery disease in Asian Indians: prevalence and risk factors. Asian Am Pac Islander J Health 1993;1:161-75.

17 Enas EA, Yusuf S, Mehta J. Prevalence of coronary artery disease in Asian Indians. Am J Cardiol 1992;70:945-9

18-Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 1997; 349: 1269–1276.

19-Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in developing countries. Circulation. 1998; 97: 596–601.

20-Wu Z, Yao C, Zhao D, et al. Sino-MONICA project: a collaborative study on trends and determinants in cardiovascular diseases in China, I: morbidity and mortality monitoring. Circulation. 2001; 103: 462–468.

21-Popkin BM, Horton S, Kim S, et al. Trends in diet, nutritional status, and diet-related noncommunicable diseases in China and India: the economic costs of the nutrition transition. Nutr Rev. 2001; 59: 379–390.

22-Yusuf S, Reddy S, Ounpuu S, et al. Global burden of cardiovascular diseases, I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001; 104: 2746–2753.

23-Stamler J, Daviglus ML, Garside DB, et al. Relationship of baseline serum cholesterol levels in 3 large cohorts of younger men to long-term coronary, cardiovascular, and all-cause mortality and to longevity. JAMA. 2000; 284: 311–318.

24-LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA. 1999; 282: 2340–2346.

25-Wu AH, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes RJ, National Academy of Biochemistry standards of Laboratory Practice recommendations for the use of cardiac markers in coronary artery diseases. Clin Chen 1999;45:1104-21

26-Roberts R, Fromm RE , management of acute coronary syndromes based on risk stratification by biochemical markers : an idea whos time has come. Circulation 1991;83:1107-9
27-Murry CJL, Lopez Ad, Global comparitive assessments in the health sector, Geneva, Swizerland:World

28-Onram AR, The epidemiological transition a theory of the epidemiology of population change. Mill bank Memorial Fund Q. 1970; 49:509-538

29-Peanson TA, Jamson DT, Trejo-Gutterrez H.Cardiovascular disease. In:Jamsom DT, ed, disease control priorities in developing countries, Newyork NY, Oxford University press, 1993:577-599

30-World Health Organization, The world health report 2002, reducing risks, promoting healthy life, Geneva, WHO 2002.

31-World development indicators 2001, The World bank, Washington 2001.

32-Human Development in South Asia 2001, Globilization and human development, human development center, Karachi (Pakistan), Oxford University press,1999.

33-WHO, Cardiovascular disease prevention and control.

34-ATLAS of heart disease and strok WHO, Sep-2004.

35-Nishtar S, Prevention of coronary heart disease in South Asia, lancet 2002:360:1015-18.

36-yours, ReddyS, Ounpuu S, Anand S, Global burden of cardiovascular disease part II.Variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 2001: 104:2855-64

37-Evas EA, Garg A, Davidsons MA, Nair VM Huet BA Yousuf S. Coronary Heart disease and its risk factors in the first-generation immigrants asian indians to the United States of America, Indian Health J, 1996 48:343-53

38-Economic survey of Pakistan 1998-99, Govt of Pakistan, Finance division, Economic advisor wing, Islamabad-2000.

39-Pakistan Medical Research Council, National Health Survey of Pakistan, 1990-94, Health profile of the people of Pakistan, Islamabad, Network publication Sciences-1998.

40-Trvelgn, J needham EW, Halim M, Singh H, Been M, Shin MF, etal. Evaluation of patient characteristics and utilization of invasive cardiac procedures in a UK Ethnic population with unstable ungina pectorisInt 1 Cardiol 2001:77:275-80

41-Reddy KS, Yousuf S Emerging epidemic of cardiovascular disease in developing countries, Circulation, 1998-97:596-601

42-World Health Organization, Health Situation in South East Asian region, 1998-2000, New Delhi, WHO 2002.

43-Pais P.Poug j Gestein H,etal, Risk factors of acut myocardial infarction in Indians, A case control study, Lancet, 1996,348:358-363.

44-Anam s EnasE, pouge J, etal, Elevated Lipoprotein levels in South Asians in North America, Metabolism 1998:47:182-84

45-Anand SS, Yousaf S, Vuksan V, etal, Differences in risk factors and atherosclerosis and cardiovascular disease in ethnic groups in Canada, the study of Health assessment and risk in ethnic groups, Lancet 2000: 365:279-284

46-Gupta R gupta VP, Sarna M etal, Prevalence of CHD and risk factors in an urban , Indian population, Jaipur Heart Watch-2 Indian heart J 2002:54:59:56.

47-Fernanded VL, kotte TE , Nicholas JJ, Tobacco consumption and CAD in Rao GHR Kakkar VV, eds, CAD in South Asians, New Delhi, Jaypee Brothers 2002-147-64.

48-Zaman MM Youshiike N, rouf MA etal, Cardiovascular risk factors, Distribution prevalence in a rural population of Bangladesh J, Cardiovasc risk 2001:8:103-08

49-Panday Mr, Newpane RP, Gaurtan A, epidemiological study of tobacco smoking among adults in a rural community of the hill region of Nepal with special reference to attitudes and beliefs, Int J Cardiol 1988:17:535:41.

50:Mendis S, Ekanayake EM, Prevalence of CHD and its risk factors in middle aged males in a different population in Central Srilanka. Int I Cardiol 1994;46: 135-42

51-Singh RB, Sharma JP, Rastogi V, etal. Prevalence of CVD and coronary risk factors in rural and urban population of North Indea, Eur Heart J 1997; 18:178-35.

52-Jafer TH, Levey AS, Jafar FH, White F, Gul A, Rahbar MH, etal. Ethnic subgroup differences in hypertension in Pakistan. J Hypertens 2003; 21:905-12

53-Syeed MA, Mahtab H, Akhter K, Latif AZ, Ali K, Bana, etal, Diabetes and impared fasting glycemia in a rural population of Bangaladesh, Diabetes care 2003; 26:1034-9

54-Gupta R, Gupta VP, Metanalysis of CHD prevalence in Indea, Indean Heart J 1996;48:241-45

55-Barker DJP, Fetal origins of CHD.BMJ 1995;311:171-4

56-Stein CE, Fall CHD, Kumaran K, Osmond C, COX V, Barke DJP, Fetal growth and coronary Heart disease in South Indea. Lancet 1996; 348:1269-73

57-Integrated management of cardiovascular risk, Report of a WHO meeting, geneva July 2002

56-A race against time, the challenge of cardiovascular disease in developing economics, 2004 Columbia University, Newyork.

7-Fernando DJS, Sirribaddana SH, De Silva Dr.Perere SD, The prevelance of obesity and other coronary risk factors  in suburban Srilankan community. Asia pac J Clin Nuk. 1995 ; 1:1-4

58-Zaman MM, Rauf MA. Prevalence of hypertension in a Bungladesh adult population. J Hum Hypertense, 1999;13:547-9

59-International diabetes fedration, Diabetes atlas 2000, Brussels:IDF:2000

60-King H, Aubert RF, Herman WH, Global burden of diabetes, 1995-2025, prevalence, numerical estimates and projections. Diabetes care 1998, 21:1414-31

61-Abu Saeed M , Ali L, Hussain MZ, Rumi MA, Banu A etal,Effects of social economical conditions in prevalence of diabetes between rural and urban populations in Bungaladesh, Diabetes care 1997;20:551-5

62-Diabetes association of Srilanka, 1999 problem causes report of Srilanka. (Questionaire performa of international diabetes fedration south east asian region of the mid term meeting, 26th March 1999)

63-Singh DL , Bhattaria MD, High prevalence of diabetes and impared fasting glycemia in Urban Nepal. Diabetes Med 2003; 20:170-1

64-International diabetes fedration 2005

65-WHO expert consultation, Apropriate body mass index for asian population and its implication for policy and interventional strategies.Lancet 2004; 363(9403):157-63

66-Mekeigue PM etal, relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in south asians. Lancet 1991;338:842-847

67-Potts J, Simmon D, Sex and ethics groups differences in fat distribution in group UK, south Asians and Europids. J Clin Epidemiol 1994;47 837-841

68-Yajnik LS, The insulin resistance epidemic in Indea, Fetal originlater lifer style, Nutr Rev 2001;59:1-9

69-Nishter S, Anthony S, Peter J, Charles N,etal, Waist HP ratio and low HDL predict the risk of CVD in Pakistan curr Med Re Opinion 20(1): 55-62;2004

70-Reddy KS, Shah P, Shirivastav U, Prabahakar D, etal. Coronary heart disease risk factors in an industrial population of North Indea. Can J Cardiol 1997;(13 suppl B) 26

71-Mendis S, Comparitive study of middle aged men in both rural and urban areas in Srilanka. Proc Ksm, 1996:18:64-94

72-Mendis S, Ekanayanke EM, Prevalence of coronary heart disease and cardiovascular risk factors in middle aged males in a defined population of central Srilanka, Int J Cardiol 1194; 46:135-42.

73-World Health Organization, Tobacco or health ? First global status report geneva, Switzerland: WHO;1996.

74-Zaman MM, Yoshiike N, Rouf MA, Syed MH, Khan MR, haques S, etal, Cardiovascular risk factors: Distribution & Prevention in a rural population of Bangaladesh, J Cardiovasc Risk, 2001;8:103-8.

75 Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994; 308:367-73.

76 Gould AL, Rossouw JE, Santanello NC, et al. Cholesterol reduction yields clinical benefit. A new look at old data. Circulation 1995; 91:2274-82.

77 Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. New England Journal of Medicine. 1995; 333:1301-7.

78- No authors listed. The effects of pravastatin on hospital admission in hypercholesterolemic middle-aged men: West of Scotland Coronary Prevention Study. J Am Coll Cardiol. 1999; 33:909-15.

privacy policy