Reappraising the Role of Eplerenone in the Management of Heart Failure

Background: In India, the prevalence of heart failure (HF) is increasing at 1.2/1,000 people according to a study in northern India, and the mortality rate at 1 year (INTERnational Congestive Heart Failure [INTER-CHF]) is 37%. Due to the diverse phenotypes of HF, nonadherence to guideline-directed medical therapy (GDMT), resistance to uptitration of medication and underuse of mineralocorticoid receptor antagonists (MRAs), such as eplerenone, a uniform management approach may not be feasible. This review is aimed at assessing the burden of HF, reasons for underutilization of MRAs in treatment, evaluating the evidence and reappraising the disease-modifying role of eplerenone in HF management. Methods: An electronic database search was performed to identify relevant literature. Results: The review details various studies that demonstrate the role of MRA eplerenone as a disease-modifying agent in patients with mild-to-moderate hypertension and those with acute myocardial infarction (MI) complicated by left ventricular dysfunction and HF. It also outlines different patient profiles for eplerenone use and ways to handle minor side-effects. Conclusions: Eplerenone shows a promising effect in selectively blocking aldosterone receptors to suppress fibrosis and reverse cardiac remodeling.

Identifying high risk patients post myocardial infarction with reduced left ventricular function using loop recorders INSPIRE-ELR clinical study

Aims: Sudden cardiac death (SCD) continues to be a devastating complication amongst survivors of myocardial infarction (MI). Mortality is high in the initial months after MI. The aims of the INSPIRE-ELR study were to assess the proportion of patients with significant arrhythmias early after MI and the association with mortality during 12 months of follow-up. Methods: The study included 249 patients within 14 days after MI with left ventricular ejection fraction (LVEF) _x0001_35% at discharge in 11 hospitals in India. Patients received a wearable external loop recorder (ELR) 5 ± 3 days after MI to monitor arrhythmias for 7 days. Results: Patients were predominantly male (86%) with a mean age of 56 ± 12 years. In 82%, reperfusion had been done and all received standard of care cardiovascular medications at discharge. LVEF was 32.2 ± 3.9%, measured 5.1 ± 3.0 days after MI. Of the 233 patients who completed monitoring (7.1 ± 1.5 days), 81 (35%) experienced significant arrhythmias, including Ventricular Tachycardia/Fibrillation (VT/ VF): 10 (4.3%); frequent Premature Ventricular Contractions (PVCs): 65 (28%); Atrial Fibrillation (AF): 8 (3.4%); chronic atrial flutter: 4 (1.7%); 2nd or 3rd degree Atrioventricular (AV) block: 4 (1.7%); and symptomatic bradycardia: 8 (3.4%). In total, 26 patients died. Mortality was higher in patients with clinically significant arrhythmia (at 12 months: 23.6% vs 4.8% with 19 vs 7 deaths, hazard ratio (HR) ¼ 5.5, 95% confidence interval (CI) 2.3 to 13.0, p < 0.0001). Excluding 7 deaths during ELR monitoring, HR ¼ 4.5, p < 0.001. Conclusion: ELR applied in patients with acute MI and LV dysfunction at the time of discharge identifies patients with high mortality risk.

Pharmacological measures to increase HDL-C among high risk isolated low HDL cases: A randomized study amongst north Indians.

Background & objectives: Low serum levels of high density lipoprotein cholesterol (HDL-C) is an established risk factor for coronary heart disease (CHD). Among a variety of lipid modifying drugs, the best single drug therapy to increase HDL-C levels, especially among high risk, isolated low HDL-C (ILHDL-C) cases is yet to be identified. The objectives of the present study were to evaluate the best pharmacological measure among atorvastatin, fenofibrate and niacin aimed to raise HDL-C and its effect in decreasing the estimated Framingham-10-year CHD risk percentage (CHD-RP) among high risk ILHDL-C cases in north India. Methods: Two hundred CHD equivalent (CHD-RP≥20), ILHDL-C cases were randomly assigned for treatment either with atorvastatin 10 mg/day (n=70), micronized fenofibrate 160 mg/day (n=65) or niacin-extended release (ER) 750 mg/day (n=65). After 6 wk of treatment, the dosages of drugs were doubled and the patients were finally assessed after 12 wk for their lipid values. Results: Baseline characteristics were similar in the three groups. Niacin therapy 750 mg and 1.5 g/day resulted in a significant rise in HDL-C by 8.10 ± 3.19 and 12.41 ± 4.39 per cent (P<0.001), respectively. Fenofibrate 160 and 320 mg/day also resulted in a significant rise in HDL-C by 3.85 ± 3.48 and 6.24 ± 4.43 per cent (P<0.001), respectively, while atorvastatin 10 and 20 mg/day resulted in a non-significant increase in HDL-C by 0.13 ± 2.92 per cent and 0.51 ± 2.63 per cent, respectively. By increasing HDL-C values, niacin was found to be most effective in reduction of 10-year CHD-RP (P<0.001), followed by fenofibrate (P=0.010), while atorvastatin had no effect. Interpretation & conclusions: Our findings indicate that niacin rather than fibrates or statins seems to provide a safe and effective therapy for increasing HDL-C, thus reducing the cumulative CHD risk among ILHDL-C cases.

Impact of comprehensive cardiovascular risk reduction programme on risk factor clustering associated with elevated blood pressure in an Indian industrial population.

Background & objectives: Cardiovascular risk factors clustering associated with blood pressure (BP) has not been studied in the Indian population. This study was aimed at assessing the clustering effect of cardiovascular risk factors with suboptimal BP in Indian population as also the impact of risk reduction interventions. Methods: Data from 10543 individuals collected in a nation-wide surveillance programme in India were analysed. The burden of risk factors clustering with blood pressure and coronary heart disease (CHD) was assessed. The impact of a risk reduction programmme on risk factors clustering was prospectively studied in a sub-group. Results: Mean age of participants was 40.9 ± 11.0 yr. A significant linear increase in number of risk factors with increasing blood pressure, irrespective of stratifying using different risk factor thresholds was observed. While hypertension occurred in isolation in 2.6 per cent of the total population, co-existence of hypertension and >3 risk factors was observed in 12.3 per cent population. A comprehensive risk reduction programme significantly reduced the mean number of additional risk factors in the intervention population across the blood pressure groups, while it continued to be high in the control arm without interventions (both within group and between group P<0.001). The proportion of ‘low risk phenotype’ increased from 13.4 to 19.9 per cent in the intervention population and it was decreased from 27.8 to 10.6 per cent in the control population (P<0.001). The proportion of individuals with hypertension and three more risk factors decreased from 10.6 to 4.7 per cent in the intervention arm while it was increased from 13.3 to 17.8 per cent in the control arm (P<0.001). Interpretation & conclusions: Our findings showed that cardiovascular risk factors clustered together with elevated blood pressure and a risk reduction programme significantly reduced the risk factors burden.

Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among north Indians.

Background: Polymorphisms in paraoxonase 1 (PON1) coding for PON1 enzyme have been studied as genetic markers of coronary artery disease (CAD). PON1 Q192R and PON1 L55M polymorphisms have been analyzed extensively, but data on association and role of these polymorphisms in the etiology of CAD are conflicting. In this study, we tested the genetic association between PON1 Q192R and PON1 L55M polymorphisms and CAD among north Indians. Materials and Methods: Two hundred eighty-five angiographically proven patients with coronary artery disease and 200 sex-matched and ethnically matched controls were genotyped for 2 PON1 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotype/ allele frequencies were compared in patients and controls using the chi-square test. Results: At PON1-192 locus, there were significant differences between patients and controls (P< 0.05), leading to significant odds ratios for RR genotype (OR= 1.92, CI: 1.19-3.10) and *R allele (OR= 1.30, CI: 1.00-1.70). These odds ratios were higher in the sub-sample of smokers (2.84 and 1.45, respectively). Binary logistic regression analysis also confirmed that *R allele carriers (QR and RR) have a higher risk of CAD (OR= 3.54, CI: 1.67-5.53). PON1-55 locus did not show significant differences between patients and controls, but LL genotype and *L allele were significant risk factors in the nonsmoker group. RL haplotype was also significantly associated with CAD risk (OR= 1.44, CI: 1.08-1.93). Conclusions: PON1-192R allele and RR genotype are significantly associated with CAD patients from the north Indian population (Uttar Pradesh). This association was stronger in smokers, supporting the conclusion that an interaction between PON1 activity and smoking augments CAD risk. Further studies with larger sample size are warranted to confirm these associations in different Indian populations.

Safety and efficacy of indigenously developed and manufactured bivalirudin in moderate/high-risk Indian patients undergoing percutaneous coronary intervention: the Bivaflo Registry.

BACKGROUND: Current treatment strategies for percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS) include concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and antithrombotic therapy such as aspirin, clopidogrel, and unfractionated or low-molecular-weight heparin. The "direct thrombin inhibitor" bivalirudin has been associated with better efficacy and safety than heparin. OBJECTIVE: The present study is performed to evaluate the safety and efficacy of an indigenously developed and manufactured bivalirudin (Bivaflo; Sun Pharmaceutical Industries Ltd., Mumbai) as the primary anticoagulation strategy during PCI in moderate-high risk patients with only provisional use of GPI. METHODS: This prospective multicentered registry enrolled 439 patients in 11 tertiary care centers across India. Patients who had ACS or other clinical/angiographic characteristics, which increase risk during PCI, were enrolled in the registry. Bivaflo was administered as a bolus dose of 0.75 mg/kg, followed by infusion at a rate of 1.75 mg/kg/h during the procedure and optionally 0.25 mg/kg/h for 4 hours after the procedure at investigator's discretion. GPI use was discouraged except as bailout. The primary endpoints were composite and individual incidences of death, myocardial infarction (MI), urgent revascularization, subacute stent thrombosis (SAT), or bleeding at day 7/hospital discharge, whichever was earlier. The secondary endpoints were 30-day composite and individual incidences of death, MI, urgent revascularization, and SAT. RESULTS: The mean age of the group was 58 +/- 10 years and 83% were males. Bivaflo was administered for a mean duration of 102 +/- 79 minutes, and 65% patients received Bivaflo infusion post-PCI. ACT values measured at 10 minutes after bolus and at the end of the PCI were found to be 339 +/- 110 and 336 +/- 104 seconds, respectively. GPI was provisionally used in only 4% (16) patients mostly due to new or suspected thrombus and obstructive dissection with decreased flow. At day 7/hospital discharge, there were no incidences of major adverse cardiac events or major bleeding. Minor bleeding occurred in only 4 patients (0.9%). The 30-day composite major adverse cardiac event rate was 0.68%. One death and two subacute thrombosis occurred during the 30-day follow-up. CONCLUSION: Bivaflo is safe and effective sole anticoagulation strategy during PCI of moderate-high risk patients. Bivaflo administration was associated with no major bleeding events and extremely low in hospital and 30-day MACE rate. These rates were lower than expected MACE rates for such a subgroup of patients based on historical controls.

Association of coronary artery disease with polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase gene.

OBJECTIVE: Angiotensin-converting enzyme plays an important role in maintaining blood pressure, while methylenetetrahydrofolate reductase is involved in homocysteine metabolism. As hypertension and elevated homocysteine levels are among the various risk factors for coronary artery disease, the two polypeptides might need to be considered while determining the risk. Our study aimed to assess the association between common polymorphisms in these genes and susceptibility to coronary artery disease. METHODS: We studied 268 north Indian individuals with coronary artery disease and 90 age-matched controls. The distribution of the genotypes and allele frequencies of both genes were analyzed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis. RESULTS: The frequency of the D allele was significantly higher among the patients (62%) than the controls (44%) (p=0.001, odds ratio=2.06). The same goes for the DD genotype (37% vs 21%) (p=0.004). The combined frequency of the D allele carriers was significantly higher among patients of coronary heart disease, with a difference of 20% (85% vs 65%) (p=0.003, odds ratio=3.1; CI: 1.3-7.29). However, the frequency of the T and C alleles, as well as that of the CC, CT and TT genotypes of the methylenetetrahydrofolate reductase gene, did not differ significantly between the two groups. CONCLUSION: We conclude that coronary artery disease in north Indian patients is strongly associated with the carrier state of the angiotensin-converting enzyme D allele, but not with the C677T transition in the methylenetetrahydrofolate reductase gene.

Premature coronary artery disease in North India: an angiography study of 1971 patients.

BACKGROUND: South Asians, specially Indians, show increased risk for atherosclerosis and have the highest mortality rates due to coronary artery disease amongst all ethnic groups studied so far. We aimed to find out the differences in clinical-biochemical and angiographic profile of young patients versus older patients with angiographically proven atherosclerotic coronary artery disease. METHODS AND RESULTS: Group I (n=828) consisted of patients with age above 55 years (mean age: 63.15 +/- 5.76 years), group II (n=924, mean age: 49.13 +/- 4.25 years) consisted of patients between age 41-55 years and group III (n=219) consisted of patients with age < or = 40 years (mean age: 37.37 +/- 2.92 years). Among the conventional risk factors, smoking was significantly more frequent in group III, while diabetes mellitus and systemic hypertension were more prevalent in groups II and I. Q wave myocardial infarction was more frequently present in groups II and III. Only about one-third of the entire patient population in the myocardial infarction group received thrombolytic therapy. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were significantly higher in younger patients (groups II and III), while high-density lipoprotein cholesterol was significantly low in whole cohort but more so in older patients. Single vessel involvement was more common in group III, while multi-vessel involvement, diffuse disease and fluoroscopic calcium were more common in groups I and II. CONCLUSIONS: Significant differences were observed in the clinical, biochemical and angiographic profile of young patients with coronary artery disease as compared to elderly patients. The younger cohort had more atherogenic lipid profile, higher prevalence of smoking and more frequent single vessel disease. We observed that total cholesterol/high-density lipoprotein cholesterol ratio was a better predictor of coronary artery disease as compared to individual lipid levels.

Association of common carotid intima-media thickness and lipoprotein(a) with coronary artery disease.

BACKGROUND: Carotid artery intimal medial thickness is a simple, non-invasive and reproducible clinical tool to evaluate atherosclerosis and predict coronary artery disease. Lipoprotein(a) levels are related to both atherogenesis and thrombogenesis and may be a key link between lipid and coronary artery disease. This study evaluated the association of carotid intimal medial thickness and lipoprotein(a) with coronary artery disease. METHODS AND RESULTS: We studied 185 randomly selected patients hospitalized for coronary angiogram in our institute. There were 110 angiographically proven patients of coronary artery disease with mean age of 55.8 +/- 9 years (range 34-72 years) and 75 subjects with normal coronary artery anatomy with mean age of 54.8 +/- 8 years (range 34-68 years). The mean carotid intimal medial thickness of subjects with coronary artery disease was significantly higher than in subjects without coronary artery disease (0.84 +/- 0.16 mm v. 0.65 +/- 0.15 mm, p<0.001). The mean carotid intimal medial thicknesses in patients with triple vessel, double vessel and single vessel disease were 0.96 +/- 0.12 mm, 0.84 +/- 0.11 mm and 0.78 +/- 0.13 mm, respectively (p=0.05). The mean lipoprotein(a) of subjects with coronary artery disease was significantly higher than in subjects without coronary artery disease (35.9 +/- 22.3 mg/dl v. 19.1 +/- 21.2 mg/dl, p<0.001). Mean lipoprotein(a) levels in subjects with carotid intimal medial thickness <0.80 was 26.4 +/- 24.2 mg/dl and in subjects with carotid intimal medial thickness > or = 0.80 was 32.1 +/- 22.1 mg/dl (p=0.05). CONCLUSIONS: There is a strong correlation between carotid and coronary atherosclerosis and carotid intimal medial thickness is a good predictor of presence and extent of coronary artery disease. Lipoprotein(a) level is a powerful independent risk factor for atherosclerosis. Carotid intimal medial thickness and lipoprotein(a) in conjoint can predict coronary artery disease reliably.

Assessment of left ventricular systolic and diastolic function in juvenile rheumatoid arthritis.

BACKGROUND AND AIMS: Recognizing the paucity of data regarding echocardiographic studies of Left ventricular (LV) systolic and diastolic function in patients with juvenile rheumatoid arthritis (JRA), a study was carried out to study these parameters in these subjects. SETTINGS, DESIGN AND METHODS: Thirty-five patients with JRA and an equal number of age- and sex-matched controls were studied by two-dimensional and Doppler echocardiography. RESULTS: Patients with JRA had higher systolic and diastolic blood pressures, resting heart rates, LV systolic (26.9+/-4.3 vs. 22.4 +/- 4.1 mm, p=0.001) and diastolic size (42.3+/-4.6 vs. 35.4+/-3.8 mm, p< 0.001) and volumes. Though ejection fraction (EF) and fractional shortening (FS) were normal, they were lower in those with JRA as compared to controls (EF: 62.9+/-4.47 vs. 67.5+/-3.63 %, p< 0.001; FS: 36.4+/-4.5 vs. 38.5 +/- 6.87, p=0.2). On Doppler analysis the JRA group had lower peak E velocity, higher peak A velocity, higher A VTI and more prolonged IVRT. Male patients had higher A VTI and IVRT as compared to females. Those with longer duration of disease had larger LV systolic (r=0.517, p=0.01) and diastolic dimension (r=0.40, p=0.05) and lower FS (r=-0.506, p=0.01). Patients with polyarticular JRA had higher E and A VTI as compared to those with systemic or oligoarticular types. CONCLUSION: Despite an asymptomatic cardiac status, significant systolic and diastolic functional abnormalities exist in patients with JRA. The duration of the disease, mode of presentation, patient's age and gender have a significant impact on the left ventricular systolic and diastolic functions in patients with JRA.

Assessment of right ventricular diastolic function: does it predict post-operative course in tetralogy of Fallot.

BACKGROUND: In some cases of tetralogy of Fallot the post-operative course is characterized by episodes of low cardiac output, elevated central filling pressures and prolonged ventilation and inotropic support. This may be due to impaired diastolic function of the right ventricle despite preservation of biventricular systolic function. METHODS AND RESULTS: Sixty-four consecutive patients (mean age 7.06+/-4.9 years) undergoing repair of tetralogy of Fallot were prospectively studied to assess right ventricular diastolic function. 'Restrictive physiology' was defined as presence of laminar antegrade diastolic pulmonary artery flow (A wave) throughout the respiratory cycle, which was coincident with atrial systole. Right ventricle restriction was present in 45/64 (70%, Group 1) patients and absent in 19/64 (30%, Group 2) patients. There was a marked inspiratory augmentation of the pulmonary artery A wave velocity, flow integral and duration. Transtricuspid flow revealed significantly lower peak E velocity, lower E/A ratio, shorter E deceleration time and higher A velocity time integral in those with right ventricular restriction. Biventricular systolic function and transmitral flow were normal in all patients. Those with restrictive physiology had significantly longer mean inotrope support duration, longer ventilation and chest drainage times. Correspondingly, the mean intensive care unit stay (56.7+/-9.3 v. 34.7+/-5.38 hours, p<0.01) and mean hospital discharge time (9.3+/-2.3 v. 6.2+/-0.5 days, p <0.001) was also significantly longer in group 1. CONCLUSIONS: Right ventricular restriction (as seen by laminar antegrade diastolic pulmonary artery flow throughout the respiratory cycle) exists in a significant subset of patients with tetralogy of Fallot following operative repair. Following surgery, such patients have higher inotropic requirement, longer ventilation times and longer hospital stay.

Coronary angioplasty in a case of quadriostial origin of coronary arteries from right aortic sinus.

We report a case in which all three coronary arteries were originating from the right aortic sinus via separate ostia, and angioplasty of the normally arising right coronary artery was performed. In addition, the conal artery was also originating separately from same sinus, actually leading to a quadriostial origin of the coronaries. A combination of anteroaortic septal course of the left anterior descending artery and retroaortic course of left circumflex artery is an unusual coronary anomaly and was noted in this case.

Angiotensin-converting enzyme gene polymorphism in coronary artery disease in north India.

BACKGROUND: The aim of this study was to investigate the role of angiotensin-converting enzyme gene polymorphism in patients with coronary artery disease in north India. METHODS AND RESULTS: One hundred forty-six patients with angiographically proven atherosclerotic coronary artery disease, and 146 age- and sex-matched control subjects (treadmill-negative) were included in the study. Genomic DNA was extracted and analyzed for angiotensin-converting enzyme insertion/deletion polymorphism. Two independent investigators scored the genotypes. CONCLUSIONS: When we compared the genotypes of patients with coronary artery disease with those of normal controls, it was seen that all three genotypes, i.e. DD, ID and II, were not statistically different among patients and controls. Further, we categorized the patient and control groups into 2 subgroups, i.e. below and above 50 years of age. Interestingly, it was observed that the DD genotype was significantly higher in patients in the higher age group (i.e. above 50 years of age). However, this needs further validation by studying patients with coronary artery disease from other parts of India.

Determinants of left atrial pressure in rheumatic mitral stenosis: role of left atrial compliance and "atrial stiffness".

BACKGROUND: A wide range of left atrial pressures exist in rheumatic mitral stenosis despite similar mitral valve area. Left atrial compliance may be an important determinant of left atrial pressure in mitral stenosis. Data regarding left atrial compliance in rheumatic mitral stenosis and changes following balloon mitral valvotomy are scarce. METHODS AND RESULTS: Left atrial compliance and predictors of left atrial pressure were analyzed in 85 patients with mitral stenosis undergoing balloon mitral valvotomy. The stroke volume was divided by systolic rise in left atrial pressure to calculate the left atrial compliance. Systolic rise in left atrial pressure was computed as difference between amplitudes of left atrial "v" wave and "x" descent. The mean left atrial compliance prior to balloon mitral valvotomy was 2.62+/-1.20 cm3/mmHg. Following successful balloon mitral valvotomy there was a significant fall in pulmonary artery pressure, mean left atrial pressure, transmitral gradient, and significant increase in cardiac output, stroke volume and mitral valve area. There was a marked increase in left atrial compliance from 2.62+/-1.20 to 6.1+/-3.16 cm3/mmHg. On univariate analysis pulmonary artery systolic pressure, pulmonary artery diastolic pressure, pulmonary artery mean pressure, mean transmitral gradient, mitral valve area and left atrial compliance were the only correlates of left atrial pressures, while no correlation was noted with age, gender, left atrial size, cardiac output and stroke volume. Those with higher pulmonary artery pressure, higher transmitral gradient, lower mitral valve area and lower left atrial compliance had higher left atrial mean pressure, and the strongest negative correlation was noted with left atrial compliance. On multivariate analysis the strongest predictors of left atrial mean pressure were transmitral gradient and left atrial compliance. CONCLUSIONS: Patients with rheumatic mitral stenosis have markedly depressed left atrial compliance and hence have "stiff" left atria. Left atrial compliance is an important determinant of left atrial pressure, and improves immediately after successful balloon mitral valvotomy, irrespective of pre-balloon mitral valvotomy left atrial pressures.

A tertiary care hospital-based study of conventional risk factors including lipid profile in proven coronary artery disease.

BACKGROUND: The prevalence and mortality rates of coronary artery disease have been known to be higher in the Indian than the Western population. Most data on lipid levels in Indians have been obtained from studies on migrant Asian Indians. There are insufficient data on lipid profile and other conventional risk factors in Indian patients living within India. METHODS AND RESULTS: The study included 2656 consecutive patients who underwent coronary angiography between March 1998 and February 2002. Of these, 2399 subjects had angiographically proven coronary artery disease (group 1) while 257 had normal coronary arteries (group 2). Lipid values were measured in the fasting state on the morning the coronary angiography was done. Patients receiving lipid-lowering agents, those having renal, hepatic or thyroid disorders, patients presenting within 8 weeks after acute myocardial infarction, and patients who were taking noncardiac drugs that affect the lipid profile were excluded from the study. Other conventional risk factors were also recorded. In subjects with coronary artery disease and normal coronary arteries, the levels of mean total cholesterol recorded were 178.5+/-42.1 mg/dl v. 154.1+/-40.2 mg/dl (p<0.001), high-density lipoprotein cholesterol 30.6+/-9 mg/dl v. 27.3+/-6.8 mg/dl (p<0.001), low-density lipoprotein cholesterol 109.8+/-35.4 mg/dl v 93.6+/-33.9 mg/dl (p<0.001), and triglyceride 190.7+/-95.4 mg/dl v. 157.6+/-73.5 mg/dl (p<0.001), respectively. In subgroup analysis by age, the younger coronary artery disease group (< or = 40 years) had significantly higher total and low-density lipoprotein cholesterol levels than the older group (> 40 years), viz. 194.6+/-51.4 mg/dl v. 176.3+/-40.2 mg/dl (p<0.001), and 118.3+/-39.6 mg/dl v. 108.7+/-36.1 mg/dl (p=0.001). Triglyceride levels were not significantly different [211.7+/-105.1 mg/dl v. 187.8+/-93.6 mg/dl (p=ns)], being equally high in both subgroups and, although high-density lipoprotein cholesterol levels were different, this difference was minimal, being equally low in both [32.7+/-9.5 mg/dl v. 30.3+/-9.0 mg/dl (p=ns)]. In the subgroup analysis of those with coronary artery disease, diabetics had significantly lower total cholesterol [174+/-41.1 mg/dl v. 180.4+/-42.4 mg/dl (p<0.001)] and low-density lipoprotein cholesterol levels [105.8+/-34 mg/dl v. 111.5+/-35.8 mg/dl (p<0.001)] than non-diabetics, whereas triglyceride and high-density lipoprotein cholesterol levels were not significantly different, triglycerides being equally high in both [186.2+/-95.5 mg/dl v. 192.5+/-95.2 mg/dl (p=ns)], and high-density lipoprotein equally low in both [30.9+/-9.3 mg/dl v. 30.5+/-9 mg/dl (p=ns)]. The commonest associated conventional risk factor in diabetics was hypertension and, in the younger age group (< or = 40 years), it was smoking and a positive family history of premature coronary artery disease. CONCLUSIONS: We conclude that in north Indians, coronary artery disease occurs at much lower levels of total cholesterol and low-density lipoprotein cholesterol than other populations, and high triglyceride and low high-density lipoprotein levels are more of a universal phenomenon in this population. 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. Total cholesterol levels seem to play a lesser role in the occurrence of coronary artery disease in diabetics, the presence of which is in itself overwhelming for the occurrence of coronary artery disease.