Serum Gamma Glutamyltransferase (GGT) in Coronary Artery Disease: Exploring the Asian Indian Connection

Background:There is a need to identify novel markers for CAD, independent of traditional CV risk factors. One of these is gamma?glutamyl transferase (GGT), a marker of increased oxidative stress. Given the high prevalence of CAD in Asian Indians, the link of GGT and CAD in them needs to be studied. Aim: To assess GGT in patients with angiographically documented CAD. Methods and Results: Two hundred patients aged 58.1 ± 9.95 years, 73% males, hypertension 56%, diabetes 40% were included. Mean GGT was 63.6 ± 44.33 (10–269 U/L). The levels of GGT progressively increased in those with single/double or triple?vessel CAD (36.5, 61.5, and 87 U/L, respectively, P < 0.001). Using objective criteria of CAD burden (SYNTAX and Gensini scores), we reaffirmed these findings. GGT in patients with SYNTAX tertiles 0–22, 23–32, and 33 was 33, 62, and 97 U/L, respectively and in Gensini tertiles 0–17.65, 17.66–56.65, ?56.66 was 32, 52, and 88 U/L, respectively, all P < 0.001. SYNTAX score 23 was present in only 23% patients in GGT tertile 1 (<41 U/L), whereas60% and 94% in GGT tertiles 2 and 3 had SYNTAX 23. Significant positive correlation was seen between GGT and SYNTAX (r = 0.634) and Gensini score (r = 0.772). Conclusions: In this study, GGT had an independent correlation with angiographic severity of CAD and SYNTAX and Gensini scores. Although the existing evidence seems biologically plausible, more studies are needed to explore the potential role of this inexpensive marker for predicting disease burden in patients with CAD.

Exploring the Association of Fibrinogen and CRP with the Clinical Spectrum of CAD and Periprocedural Outcomes in Patients Undergoing Percutaneous Coronary Interventions

Background:The pathophysiology of an atherosclerotic plaque is mediated by the mechanisms involving thrombus formation and systemic inflammation. While C-reactive protein (CRP) levels are useful in predicting a cardiovascular event in intermediate risk population, the usefulness of routinely measuring fibrinogen in patients with acute coronary syndrome (ACS) is debatable. Also, data on the association of these markers with periprocedural outcomes in patients undergoing percutaneous coronary interventions (PCI) is scarce. Aims: The study aimed to determine whether the levels of fibrinogen and CRP vary across the different spectra of CAD and whether they have any correlation with cardiac Troponin I levels. Materials and Methods: A total of 284 patients with coronary artery disease undergoing percutaneous coronary intervention were included in the study. Complete blood count, serum lipid profile, serum CRP, fibrinogen, and troponin I were measured for all patients. Results: Patients with STEMI had significantly higher levels of CRP as compared to those with unstable angina (USA) and chronic stable angina (CSA). Patients presenting with ACS had significantly higher baseline fibrinogen as compared to those with CSA. A significant positive correlation between CRP and admission Troponin I (r = 0.50; P < 0.05) as well as fibrinogen and admission troponin I (r = 0.30; P < 0.05) was observed. The CRP levels were significantly higher in 15 patients with periprocedural MI as compared to those who did not develop periprocedural MI. Conclusions: The levels of the markers of inflammation and atherothrombosis vary with presentation across varied spectra of CAD with generally higher levels in acute presentation and in those who develop periprocedural MI.

Is Indexed Left Atrial Volume (LAVi) in Indian Patients with Acute Coronary Syndrome (ACS) Undergoing Revascularization a Predictor of Cardiovascular Outcomes?

Background: Left atrial volume indexed to body surface area (LAVi) is the recommended method for LA size quantification. Assessing LAVi in Indian patients undergoing coronary interventions for acute coronary syndrome (STEMI, NSTEMI, and UA) is clinically relevant. Methods and Results: Amongst 190 patients (66.4 yrs, 68.4% males), 29.5%, 40.5%, and 30% respectively had STEMI, NSTEMI and UA. Mean LAVi was 32.29 ± 12.06 ml/m2 and 111 (58.4%) had LAVi ?32 while 79 (41.6%) had LAVi <32. Patients were divided into 2 groups (group 1 LAVi >32 and group 2 LAVi <32). Group 1 patients had higher prevalence of TVD [n = 49 vs n = 5, p = <0.001] and higher mean Syntax score (24.47 vs 14.64, p = <0.001). Despite similar LVEF, those with higher LAVi had had higher incidence of mild MR (50.4 vs 27.8, P = 0.0002) and moderate/severe MR was present only in Group 1 patients (27.9% and 5.4%). Grade I, II, and III diastolic dysfunction was present in 71.2, 17.1, and 9.9% patients in Group 1 vs 45.6%, 0%, and 0% in group 2. Diastolic parameters like septal E/e’ and lateral E/e’ratio were also higher in Group 1. Major adverse cardiovascular events? (MACE) at 30 days was significantly higher in group 1 (20.7 vs 6.3%, P = 0.006). On multivariate analysis, triple vessel disease and LAVi were the only predictors of MACE while LVEF was not. ROC curve analysis for LAVi demonstrated that a cut?off 33.35 ml/m2, predicted 30 day MACE with Area under curve (AUC) 0.775 (95% CI 0.700?0.850); sensitivity and specificity of 86.7% and 61.4%. Inter?quartile analysis of LAVi (<26.3, 26.3?33.35, 33.36?36.3, and >36.3 ml/m2) demonstrated that 30 day MACE increased across quartiles (4.16%, 4.25%, 22.44%, and 28.26%, respectively, P < 0.001). Conclusion: Amongst patients with ACS undergoing revascularization, those with higher LAVi had more severe CAD, diastolic dysfunction and higher 30 day MACE. LAVi provides superior prognostic information as compared to conventional LV systolic and diastolic parameters in patients with ACS and should be incorporated in routine echocardiographic analysis. More studies with larger numbers and longer follow up are required to further elucidate on this.

Heart rate manipulation in dilated cardiomyopathy: Assessing the role of Ivabradine

Background Heart rate (HR) reduction is of benefit in chronic heart failure (HF). The effect of heart rate reduction using Ivabradine on various echocardiographic parameters in dilated cardiomyopathy has been less investigated. Methods Of 187 patients with HF (DCM, NYHA II–IV, baseline HR > 70/min), 125 patients were randomized to standard therapy (beta blockers, ACEI, diuretics, n = 62) or add-on Ivabradine (titrated to maximum 7.5 mg BD, n = 63). Beta-blockers were titrated in both the groups. Results At 3 months both groups had improvement in NYHA class, 6 min walk test, Minnesota Living With Heart Failure (MLWHF) scores and fall in BNP, however the magnitude of change was greater in Ivabradine group. Those on Ivabradine also had lower LV volumes, higher LVEF (28.8 ± 3.6 vs 27.2 ± 0.5, p = 0.01) and more favorable LV global strain (11 ± 1.7vs 12.2 ± 1.1, p = <0.001), MPI (0.72 ± 0.1 vs 0.6 ± 0.1, p = <0.001), LV mass (115.2 ± 30 vs 131.4 ± 35, p = 0.007), LV wall stress (219.8 ± 46 vs 238 ± 54) and calculated LV work (366 ± 101 vs 401 ± 102, p = 0.05). The benefit of Ivabradine was sustained at 6 months follow up. The % change in HR was significantly higher in Ivabradine group (−32.2% vs −19.3%, p = 0.001) with no difference in blood pressure. Resting HR < 70/min was achieved in 96.8% vs 27.9%, respectively in the two groups. Conclusion Addition of Ivabradine to standard therapy in patients with DCM and symptomatic HF and targeting a heart rate < 70/min improves symptoms, quality of life and various echocardiographic parameters.

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.

Metabolic syndrome & Framingham Risk Score Observations from a coronary angiographic study in Indian patients.

Background & objectives: Metabolic syndrome (MS) is an important determinant of cardiovascular (CV) risk. Framingham Risk Scores (FRS) often underestimate the CV risk in Asians, younger patients and those with MS. Asians often develop coronary artery disease (CAD) at a younger age and also have a high prevalence of MS. Only limited data are available on the relationship between MS and FRS in such patients and the present study was undertaken to report on this aspect in an Indian patient population with angiographically documented CAD. Methods: Two hundred patients undergoing coronary angiography during a three months study period were included. Diagnosis of MS was based on modified south Asian guidelines. Results: Of the 200 patients (age 56.5 ± 8.6 yr) undergoing coronary angiography, MS was diagnosed in 77 per cent n=154; abdominal obesity, low HDL and hypertension were the commonest of the diagnostic criteria of MS, being present in >70 per cent cases. Patients with MS had significantly higher mean FRS than those without MS (15.1 vs 8.65, P<0.0001). Most patients with MS (74%, n=148) had an intermediate to high 10-year CV risk (>10%) as estimated by FRS. The proportion of patients with MS progressively increased in those with low, intermediate and high FRS (61, 87 and 92%, respectively). Though the prevalence of MS was uniformly similar (74-84%) in all age groups (<45, 45-55, 55-65 and > 65 yr, respectively), amongst those <45 yr, none of the patients could be categorized as having high CV risk as estimated by FRS despite having angiographic CAD, highlighting the limitation of age dependence of FRS. Interpretation & conclusions: MS is common in Indian patients with angiographically documented CAD; most patients with MS have 10-year risk of >10 per cent as estimated by FRS. Though MS is uniformly prevalent across all age groups, using the FRS may underestimate the CV risk in Indian patients despite documented CAD. These findings have significant implications for Asian patients with CAD in whom onset of CAD is often at a younger age than their Western counterparts. There should be continued health care emphasis on detection of MS and intensification of targeted preventive strategies.

Association of homocysteine and methylene tetrahydrofolate reductase (MTHFR C677T) gene polymorphism with coronary artery disease (CAD) in the population of North India

The implications of the methylene tetrahydrofolate reductase (MTHFR) gene and the level of homocysteine in the pathogenesis of coronary artery disease (CAD) have been extensively studied in various ethnic groups. Our aim was to discover the association of MTHFR (C677T) polymorphism and homocysteine level with CAD in north Indian subjects. The study group consisted of 329 angiographically proven CAD patients, and 331 age and sex matched healthy individuals as controls. MTHFR (C677T) gene polymorphism was detected based on the polymerase chain reaction and restriction digestion with HinfI. Total homocysteine plasma concentration was measured using immunoassay. T allele frequency was found to be significantly higher in patients than in the control group. We found significantly elevated levels of mean homocysteine in the patient group when compared to the control group (p = 0.00). Traditional risk factors such as diabetes, hypertension, smoking habits, a positive family history and lipid profiles (triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol), were found significantly associated through univariate analysis. Furthermore, multivariable logistics regression analysis revealed that CAD is significantly and variably associated with diabetes, hypertension, smoking, triglycerides and HDL-cholesterol. Our findings showed that MTHFR C677T polymorphism and homocysteine levels were associated with coronary artery disease in the selected population.

Genetic predisposition of E-selectin gene (S128R) polymorphism in patients with coronary artery disease (CAD).

Background & objectives: A surface glycoprotein molecule, E-selectin is involved in adhesion of circulating leukocyte to the activated endothelium and plays a fundamental role in pathogenesis of atherosclerosis. The present study was undertaken to document the status of S128R polymorphism of E-selectin gene in angiographically proven coronary artery disease (CAD) patients from Uttar Pradesh. Methods: Genotype of the S128R polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 329 angiographically proven CAD patients [n=83 acute myocardial infarction (AMI) and n= 246 AMI-free] and 331 age and sex matched control individuals (angiographically proven not to have CAD). Results: This pilot study revealed a significant association of R allele in coronary artery disease patients in univariate analysis [allele frequency 9.6% in patients vs. 5.6% in control (P = 0.031, OR = 1.57, 95% CI = 1.05 – 2.47)]. However, after binomial logistic regression the significant determinants of CAD were: presence of diabetes (OR: 2.26, P=0.001) hypertension (OR = 2.61, P=0.001), smoking habit (OR=2.038, P=0.001), elevated serum triglycerides (OR=1.967, P=0.001) and low HDL-C (high density lipoprotein cholesterol) (OR=1.107, P=0.001). Interpretation & conclusions: The interaction of classical risk factors for CAD with S128R polymorphism in our study population showed that the significant determinants of coronary artery disease were presence of diabetes, hypertension, smoking habit, elevated serum triglycerides and low HDL. S128R polymorphism in E-selectin gene was not an independent predictor of CAD in our population.

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.

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.

Polymorphisms in the apolipoprotein B-100 gene: association with plasma lipid concentration and coronary artery disease.

BACKGROUND: The aim of this study was to investigate the association of apolipoprotein B gene polymorphisms with coronary artery disease and lipid levels in Indians. METHODS AND RESULTS: One hundred patients of angiographically proven atherosclerotic coronary artery disease and one hundred age- and sex-matched control subjects (treadmill negative) were included in the study. Serum lipids including cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, and apolipoprotein B were analyzed. Genomic DNA was extracted and the apolipoprotein B 3' hypervariable region amplified by polymerase chain reaction. Regions carrying Xba1, EcoR1, and Msp1 restriction sites present in the apolipoprotein B gene were amplified and digested separately by the respective enzymes. Restriction fragment length polymorphism analysis showed that EcoR1 with the R+/R+ genotype was significantly more common in patients with coronary artery disease. Overall, the genotypes EcoR1+/+, Msp1+/+, Xba1+/+ and Eco R1+/+ Msp1+/-, Xba1-/- were significantly more common in patients as compared to controls (p<0.05). When gene polymorphisms were compared with lipid abnormalities, the genotypes EcoR1+/+, Xba1-/-, and Msp1+/+ were more frequent in patients with elevated apolipoprotein B and very low-density lipoprotein levels. On the other hand, these genotypes were less common in patients with increased total cholesterol and low-density lipoprotein levels. When we studied the individual alleles of the variable number of tandem repeats region, we observed that allele 34 was significantly increased in patients with coronary artery disease as compared to controls. Allele 36 was present with a frequency of 1% in controls while it was totally absent in patients. CONCLUSIONS: This study identifies the apolipoprotein B gene polymorphism associated with coronary artery disease. An association between apolipoprotein B gene polymorphisms and elevated apolipoprotein B and very low-density lipoprotein levels was observed. However, there was no positive association with other elevated lipid levels in North Indians from Uttar Pradesh.

Predictive accuracy of commissural morphology and its role in determining the outcome following Inoue balloon mitral valvotomy.

BACKGROUND: Commissural morphology is an important predictor of outcome following balloon mitral valvotomy. The aim of this prospective study was to assess if the site of commissural splitting could be reliably predicted by echocardiography and whether the extent of commissural split affected the result of balloon mitral valvotomy. METHODS AND RESULTS: A total of 140 patients (mean age 29.1+/-8.6 years) were studied. Prediction of splitting was done based on the presence of echolucent dark zones as seen in the parasternal short-axis view on echocardiography. Of 102 patients in whom a split of both commissures was predicted, the prediction was accurate in 86% (88/102). Of 33 patients with a predicted unilateral split, the accuracy of prediction was 82% (27/33). In the 5 patients with bilateral commissural fibrosis (in whom none of the commissures were predicted to split), all had a unilateral split. Overall, 93 patients (66%) had a bilateral commissural split, 43 (31%) had a unilateral split, and 4 had no commissural split. All the latter 4 developed moderate-to-severe mitral regurgitation. Those with bilateral commissural split following balloon mitral valvotomy had lower transmitral gradients (5.53+/-1.46 v 7.4+/-1.2 3 mmHg, p = 0.03) and greater mitral valve area (1.83+/-0.15 v. 1.64+/-0.15 cm2, p<0.02), as compared to those with unicommissural split. The incidence of an increase in mitral regurgitation by > or = grade 1 was also lower in the former group (7.5% v. 28%). An optimal result with the first dilatation (using a balloon size <2 mm of the predicted size) was achieved more frequently in those with a bilateral split (18% vs 8%). Oversizing of the balloon by 2 mm (of the predicted size) was done more frequently (19% v. 7%) in those with unicommissural split. CONCLUSIONS: We conclude that the assessment of commissural morphology is possible with excellent predictive accuracy. In this study, those with bilateral commissural split had more favorable hemodynamic results with lower transmitral gradients. greater mitral valve area and lesser frequency of mitral regurgitation in contrast to those with unicommissural split.