Association between genetic loci linked to HDL-C levels and Indian patients with CAD: a pilot study.

OBJECTIVE: To examine the association between loci linked to high-density lipoprotein cholesterol (HDL-C) levels and coronary artery disease (CAD). METHODS: A pilot study consisting of age-matched and gender-matched angiographically confirmed CAD cases (n=150) and non-CAD controls (n=150) was performed to test an association. Illumina's Human Cardio-Metabo BeadChip containing 3112 variants associated with HDL-C levels was used for genotyping. RESULTS: A preliminary analysis identified 36 variants from 16 genes that were statistically significant (p<0.05) between cases and controls. However, none of the variants remained statistically significant after correction for multiple testing. Besides, variants rs11039159 (MADD), rs749067 (MADD), rs367070 (LILRA3) and rs330921 (PPP1R3B) showed modest association with HDL-C levels. CONCLUSIONS: None of the HDL-C associated loci included in this study were found to be a significant risk factor for CAD. However, the study could replicate the findings of four variants influencing HDL-C levels.

Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population.

WHAT IS KNOWN AND OBJECTIVE: Statins form the backbone of lipid-lowering therapy for the prevention of cardiovascular disease. However, there is large interindividual variability in clinical response to statin treatment. Several gene variants that can be aligned to either the pharmacokinetics or pharmacodynamics of statin have been proposed as potentially important determinants of statin response. We aimed to study the association of known variations in SLCO1B1, CYP3A4, ABCB1, CYP3A5, ABCG5 and CYP7A1 genes with lipid levels in response to atorvastatin therapy. METHODS: Genotypes were determined using multiplex allele-specific polymerase chain reaction in 177 Indian patients, treated with 10 mg of atorvastatin for 8 weeks. Low-density lipoprotein-cholesterol (LDL-C) levels were recorded at baseline and after 8 weeks of atorvastatin treatment. RESULTS AND DISCUSSION: A total of 177 hypercholesterolaemic patients were genotyped to study genetic determinants of atorvastatin response. The genotype distribution for all polymorphisms investigated was in Hardy-Weinberg equilibrium. In our study, patients with wild-type genotypes of CYP7A1 (rs3808607), CYP3A4 (rs2740574), SLCO1B1 (rs2306283) and variant allele-carrying genotype of ABCB1 (rs2032582, rs1045642) showed significantly greater LDL-cholesterol reductions in response to atorvastatin therapy. WHAT IS NEW AND CONCLUSION: The variable response to atorvastatin therapy in terms of LDL-cholesterol lowering due to genetic variations in CYP7A1, CYP3A4, SLCO1B1 and ABCB1 is a promising finding. Further validation in large Indian cohorts is required before it can be assessed for clinical utility.

Left ventricular function in end stage renal disease--non-invasive assessment in patients on maintenance hemodialysis.

Non-invasive assessment of left ventricular function was performed by echocardiography and radionuclide ventriculography in 17 end-stage renal disease patients on maintenance hemodialysis. Patients with diabetes mellitus, ischemic heart disease and pericardial or valvular heart disease were excluded from the study. Parameters studied on echocardiography were left ventricular internal diameter in diastole (LVIDd), left atrial diameter (LAD), Aortic root diameter (ARD), Left ventricular posterior wall thickness in systole (LVPWs), End diastolic volume (EDV), End Systolic volume (ESV), fractional shortening percentage (FS%) and ejection fraction (EF). Parameters studied on radionuclide ventriculography were Peak ejection rate (PER), Peak filling rate (PFR) and Ejection fraction (EF). Significantly abnormal values for echocardiographic parameters LVIDd, LVPWs, EDV, ESV and FS% were found. On evaluation by MUGA scans, it was observed that the PER was significantly decreased while the PFR and EF did not change significantly.

Balloon angioplasty for native aortic coarctation.

From May 1987 to August 1990, eighteen patients underwent balloon angioplasty for native aortic coarctation. The age of the patients ranged from four to fifty six years (mean age 17.5 years). The procedure was successful in all cases with a reduction in the peak gradient across the coarctation from 61 +/- 19 mm Hg to 11.7 +/- 8.1 mmHg (p < 0.05). The coarcted segment increased from 4.5 +/- 1.9 mm to 10.7 +/- 3.9 mm (p < 0.05). Peak gradient at six to twelve months follow up, obtained in ten patients, was 19.8 +/- 10.1 mmHg (p = NS). There were no life threatening complications, although seven patients had local vascular problems after the procedure. In two patients, there was persistence of hypertension necessitating drug therapy. On haemodynamic and angiographic restudy in 10 patients, one patient had restenosis and none had aneurysm formation. We conclude that balloon angioplasty is a safe, and less invasive alternative to surgery for native aortic coarctation with gratifying immediate and short term results.

Long term results of percutaneous transluminal valvuloplasty in patients with valvular aortic stenosis.

The results of percutaneous balloon aortic valvuloplasty (PBAV) in 62 consecutive patients with valvular aortic stenosis are reported. The age of the patients ranged from 11 months to 72 years (mean 28 +/- 12 years). Hemodynamically successful dilatation was achieved in 58 out of 62 patients. This was associated with marked clinical improvement in these patients. The left ventricular aortic peak to peak gradient decreased from 96.67 +/- 38.4 to 28.14 +/- 26.5mmHg (p < 0.01). There were no deaths during the procedure. Only one patient died in the hospital during the same admission. There was an increase in aortic regurgitation (AR) by at least one grade in 25 (40.3%) patients. Femoral arterial thrombosis was seen in 9/62 patients, 5 of them requiring surgical intervention. Follow up was available in 28 (45.1%) patients over a period of 2-15 months (mean 9 +/- 3 months). Two patients died during the follow up period. Doppler evaluation of gradients was done in all 28 patients with 15 consenting to undergo repeat cardiac catheterisation. Although hemodynamically the restenosis rate was 35.7% (10/28), only 2 of these patients showed symptomatic deterioration. The success of dilatation and restenosis rate were independent of the etiology of aortic stenosis, presence of calcification and the number of balloons used. This study demonstrates that PBAV is feasible in valvular aortic stenosis at low risk and is able to produce significant clinical and hemodynamic improvement in most cases with a restenosis rate of 35.7% at a follow up period of 9 +/- 3 months.

Acute myocardial infarction with normal coronary arteries in a case of polyarteritis nodosa: possible role of coronary artery spasm.

A 20 year old man with no previous history of heart disease presented with acute left ventricular failure following extensive anterior wall myocardial infarction. Selective angiography revealed multiple aneurysms in the renal, mesenteric and hepatic arteries with an infarct in the lower pole of the right kidney. These findings, along with the presence of circulating hepatitis B surface antigen favoured the diagnosis of polyarteritis nodosa. In view of normal coronary angiogram and absence of myocardial vasculitis, coronary vasospasm was implicated as the cause of myocardial infarction. Such an occurrence, which could have different therapeutic and diagnostic implications, has not, to our knowledge, been previously described in polyarteritis nodosa.

Successful balloon valvotomy in isolated congenital tricuspid stenosis.

Isolated congenital tricuspid valve stenosis is a rare entity. The modalities of definitive treatment have been surgical repair or replacement. We present the first reported patient with congenital tricuspid stenosis successfully treated by percutaneous balloon valvotomy. This appears to be an alternative to surgery when the anatomy, as demonstrated by echocardiography, is suitable.

Unusual case of pacemaker lead migration.

Pulmonary artery migration of pacemaker lead is rare and may result in pulmonary emboli originating from the thrombus around the infected catheter and causing multiple pulmonary infarcts. We report an unusual case of pacemaker lead migration to the right pulmonary artery with septic pulmonary embolism. While being treated with intravenous Cefuroxamine, the patient had spontaneous migration of the lead to the left pulmonary artery with subsequent left pulmonary embolism.