Yash Paul Sharma

Paraoxonase 1 (PON1) Polymorphisms, Haplotypes and Activity in Predicting CAD Risk in North-West Indian Punjabis

Background Human serum paraoxonase-1 (PON1) prevents oxidation of low density lipoprotein cholesterol (LDL-C) and hydrolyzes the oxidized form, therefore preventing the development of atherosclerosis. The polymorphisms of PON1 gene are known to affect the PON1 activity and thereby coronary artery disease (CAD) risk. As studies are lacking in North-West Indian Punjabis, a distinct ethnic group with high incidence of CAD, we determined PON1 activity, genotypes and haplotypes in this population and correlated them with the risk of CAD. Methodology/Principal Findings 350 angiographically proven (≥70% stenosis) CAD patients and 300 healthy controls were investigated. PON1 activity was determined towards paraoxon (Paraoxonase; PONase) and phenylacetate (Arylesterase; AREase) substrates. In addition, genotyping was carried out by using multiplex PCR, allele specific oligonucleotide –PCR and PCR-RFLP methods and haplotyping was determined by PHASE software. The serum PONase and AREase activities were significantly lower in CAD patients as compared to the controls. All studied polymorphisms except L55M had significant effect on PONase activity. However AREase activity was not affected by them. In a logistic regression model, after adjustment for the conventional risk factors for CAD, QR (OR: 2.73 (1.57–4.72)) and RR (OR, 16.24 (6.41–41.14)) genotypes of Q192R polymorphism and GG (OR: 2.07 (1.02–4.21)) genotype of −162A/G polymorphism had significantly higher CAD risk. Haplotypes L-T-G-Q-C (OR: 3.25 (1.72–6.16)) and L-T-G-R-G (OR: 2.82 (1.01–7.80)) were also significantly associated with CAD. Conclusions In conclusion this study shows that CAD patients had lower PONase and AREase activities as compared to the controls. The coding Q192R polymorphism, promoter −162A/G polymorphism and L-T-G-Q-C and L-T-G-R-G haplotypes are all independently associated with CAD.

Cardiac abnormalities in acute organophosphate poisoning

Background. Potentially lethal cardiac complications can occur in patients with acute organophosphate poisoning (OPP) and may be overlooked. Patients and Methods. Thirty-six patients with acute OPP were studied. Clinical features and the nature of compound involved were recorded. The QT interval was plotted against heart rate to determine the risk for Torsades de Pointes using the Fossa nomogram. Echocardiography was undertaken in 29 patients. Twenty-four-hour Holter monitoring was performed on day 1 in five patients. Thirteen died. Necropsy was performed and hearts were studied both grossly and microscopically. Results. Gross examination of the heart in 13 cases revealed cardiac discoloration or blotchiness in 12, patchy pericarditis in six, auricular thrombus in six, right ventricular hypertrophy in four, and dilatation in three. On histopathology, all 13 cases had myocardial interstitial edema and vascular congestion, eight had patchy interstitial inflammation, two had patchy myocarditis, and six had a mural thrombus. Sinus tachycardia was the most common electrocardiographic abnormality. The others were corrected QT interval prolongation, ST–T changes, U waves, and ventricular premature contractions. Echocardiography in 29 patients showed minor abnormalities in 10. On Holter monitoring, episodic tachycardia and ST–T changes were observed in four, QT prolongation in three, and episodic bradycardia in two. Conclusions. Patchy myocardial involvement as a result of direct cardiac toxicity could be one of the factors responsible for serious cardiac complications. As myocardial involvement is patchy, it may not be manifest clinically or on echocardiography. Continuous cardiac monitoring should be undertaken to detect dynamic cardiac changes.

A combination of proatherogenic single-nucleotide polymorphisms is associated with increased risk of coronary artery disease and myocardial infarction in Asian Indians.

Common single-nucleotide polymorphisms (SNPs) in genes of lipid metabolism modestly influence plasma low-density lipoprotein cholesterol (LDL-C) and risk of coronary artery disease (CAD). We evaluated a panel of LDL-C-modulating SNPs for potential association with risk of CAD in Asian Indians. Fifteen SNPs of CETP, ABCB1, APOAI, CYP7A1, and HMGCR genes were genotyped in 265 CAD patients and 150 controls of North Indian origin. A proatherogenic genotype score was formulated based on number of alleles associated with LDL-C and was evaluated for association with risk of CAD. We observed 12 SNPs from CETP, APOAI, ABCB1, CYP7A1, and HMGCR genes to be associated with baseline LDL-C and high-density lipoprotein cholesterol levels and increased risk of CAD (p < 0.05). Co-occurrence of three or more risk alleles (proartherogenic genotype score >or=3) was associated with increased risk of CAD and myocardial infarction. Analysis of epistatic interactions revealed CETPTaqIB1B1/405II/APOAI-75GA to be best model of CAD risk prediction in our population. Our study highlights synergistic association of multiple SNPs of lipid pathway with LDL-C levels and risk of CAD, and indicates that co-occurrence of proatherogenic risk alleles may provide incremental information about CAD risk beyond lipid concentrations.

Cardiac dysfuntion after acute subarachnoid hemorrhage: neurogenic stress cardiomyopathy or takotsubo cardiomyopathy.

304 Neurology India | Mar-Apr 2011 | Vol 59 | Issue 2 [Figure 1a]. Diffusion-weighted imaging showed an acute infarction in the left medulla and left posterior inferior cerebellar artery (PICA) territory [Figure 1b]. Although 3-D CT angiography performed 5 days after the symptom onset showed normal vertebral artery, we suspected left vertebral artery injury caused by acupuncture. We chose conservative management strategy and the patient recovered gradually over 1 month.

Automated diagnosis of coronary artery diseased patients by heart rate variability analysis using linear and non-linear methods

Abstract Coronary artery disease (CAD) is a highly considered dangerous disease which may lead to myocardial infarction and even sudden cardiac death. The objective of this work is to evaluate the diagnostic performance features derived from linear and non-linear methods of Heart Rate Variability (HRV) analysis for classification software modules with Normal (NOR) subjects and CAD patients. The proposed methodology follows the recording of electrocardiogram from 60 NOR subjects and 64 CAD patients, RR interval tachogram generation, computing the features from time domain, frequency domain, non-linear methods and its analysis, feature dimension reduction by Principal Component Analysis (PCA) and classification by probabilistic neural network, K nearest neighbour and Support Vector Machine (SVM) classifiers. The results of the study indicate a clear difference in NOR subjects and CAD affected patients by using PCA-SVM classifier with an accuracy of 91.67%, sensitivity of 86.67% and 96.67% for NOR and CAD classes, respectively.

A rare cause of ascites in a renal transplant recipient

Thirty-five-year-old man, underwent renal transplantation 4 years back and was doing well. He now presented with complaints of ascites with engorged neck veins and dyspnoea on exertion for last 6 months. Examination showed elevated jugular venous pressure with two prominent descents, high pitched diastolic heart sound (pericardial knock). Echocardiography showed characteristic features of thickened pericardium, septal bounce, expiratory flow reversal in hepatic veins and phasic variation of mitral inflow, suggestive of constrictive pericarditis. The patient was started on empirical antitubercular therapy and diuretics. The patient symptomatically improved, but in view of persisting constrictive physiology he was planned for pericardiectomy.

Prevalence of Coronary Artery Disease in Patients of Rheumatic Heart Disease

Background : Few studies have focused on the prevalence of CAD in RHD. Coronary angiography should be routinely done in patients of valvular heart disease prior to surgery, especially in patients above 40 years of age. Overlooking CAD can lead to complications and poor results in post-operative period of valvular surgery. Clinical symptoms are common in both CAD and RHD. Indian studies by V. Jacob Jose and Satya N Gupta have studied this aspect in detail and their results are quite different from Western literature. Material & Methods : This study was conducted in all patients of valvular heart disease (RHD) above 40 years of age. Apart from basic investigations and echocardiography, coronary angiogram was done in all patients and were evaluated for presence of CAD (significant ≥ 50% or insignificant). They were also evaluated for SVD/DVD or TVD and risk factors (hypertension, diabetes mellitus, dyslipidemia) and symptoms especially angina were correlated to the presence of CAD. Results : Out of the 100 patients of RHD from Jan 2008- June 2009 at PGIMER, Chandigarh, 38 were males and 62 were females. 12 had significant CAD, while 9 had non-significant CAD. Mean age for significant CAD was 52.58 years. Age distribution was statistically significant in the 51-60 year age group. 66 patients had mitral valve disease, 31 had combined mitral and aortic valve disease, while 3 had predominantly aortic valve disease. Angina was the only symptom which correlated with presence of CAD especially in aortic valve disease group, but p value was non-significant. In risk factor category, only hypertension and total cholesterol were statistically significant with CAD. Conclusion : Prevalence of significant CAD was 12%. 5 patients had SVD, 4 had DVD & 3 had TVD. 2 patients with MS, 4 with MS/MR, 4 with MV+AV and 2 with predominant aortic valve group had significant CAD. Angina was not found to be a useful clinical symptom to predict CAD. Hypertension and total cholesterol were the only risk factors which could be correlated with CAD in RHD group.

Blood cellular mutant LXR-α protein stability governs initiation of coronary heart disease

AIM To investigate the role of [breast and ovarian cancer susceptibility 1 (BRCA1)-associated RING domain 1 (BARD1)]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-α (LXR-α) protein in coronary heart disease (CHD) subjects. METHODS The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts. Immunoprecipitation experiments were performed to establish protein interactions between LXR-α and BARD1. Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-α protein in CHD subjects by BARD1/BRCA1 complex. RESULTS The expression of mutant LXR-α protein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong negative correlation, r = -0.975 at P < 0.001. Further, the expression of BARD1 and BRCA1 also increased with the disease severity, r = 0.895 and 0.873 respectively (P < 0.001). Immunoprecipitation studies established that BARD1/BRCA1 complex degrades mutant LXR-α via ubiquitination. The absence of functional LXR-α protein resulted in increased expression of inflammatory cytokines such as interleukin (IL)-6, IL-8 and interferon-γ and decreased expression of ABCA1 (ATP-binding cassette A1) (r = 0.932, 0.949, 0.918 and -0.902 with respect to Gensini score; P < 0.001). Additionally, cell culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-α and restore its functional activity to some extent. CONCLUSION Mutant LXR-α protein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.

Precision in cardiology: should all cases of myocardial infarction with ventricular septal rupture require early repair?

Though the incidence of ventricular septal rupture (VSR) after myocardial infarction (MI) has reduced from 3%1 to 0.2%2 due to improvements in cardiac pharmacotherapy and intervention, the mortality rate still exceeds 87%1 in medically managed patients. The median time period between MI onset to VSR detection was 16–24 h 2 It has been described to occur in a bimodal pattern—within 24 h and between 3 and 5 days after MI.3 It is considered a surgical emergency as it causes cardiogenic shock and worsens the haemodynamics and rapidly culminates in death. The mortality rate in surgically treated patients varies between 20% and 60%.4 ,5This heterogeneity is attributable to timing of surgery for VSR, cardiogenic shock and recurrence of VSR. Independent predictors of mortality include posterior VSR, cardiogenic shock, inferior MI and renal failure. Because of the dismal prognosis associated with VSR, American College of Cardiology and American Heart Association recommends immediate surgical repair. But various studies illustrate the improved mortality rate when the surgery was done after haemodynamic stabilisation.5 ,6 In a largest study, the operative mortality rate was 54% when the surgery was done within 7 days and it reduced to 18% when the surgery was done after 7 days.5 The mortality was quite high when the surgery was done in an emergency basis, especially within 6 h of MI.5 Thiele et al 6 described a higher mortality rate of 83% with early surgical repair of post-MI VSR and a lower mortality rate of 29% with delayed repair after initial medical stabilisation and haemodynamic support. The mortality seen with the use of intra-aortic balloon pump (IABP) was 56.5% in that study. Papalexopoulou et al 7 described the operative mortality in early repair group to be around 31–75% and in the late repair group to be …

Coronary aneurysm after drug-eluting stent implantation

A 50-year-old hypertensive female with a diagnosis of anterior-wall non-ST elevation myocardial infaction underwent a coronary angiogram which showed a critical stenosis of ostial left anterior descending (LAD) artery with plaque in the distal left main (LM). The left circumflex (LCX) and right coronary arteries were normal with a …