Adiponectin-resistin index and its strong association with acute coronary syndrome in South Indian men.

BACKGROUND: India has the highest burden of acute coronary syndromes worldwide. Apart from certain lipid alterations that have been established to be definite risk factors, low level of adiponectin, high levels of resistin, and IL-6 have been shown to be risk factors for cardiovascular events. Insulin resistance is also a significant predictor of poor outcome in patients admitted with ACS. METHODS: 69 male patients with ACS and 70 age-matched healthy males were recruited in the study. Insulin, total adiponectin, resistin, and IL-6 levels were assayed in all study subjects. Indices of insulin resistance and novel adipokine indices were calculated using standard formulae. Multiple logistic regression analysis was done to find out the best predictor of ACS. RESULTS: Resistin, IL-6, insulin resistance indices, AR index, and IRAR index were found to be significantly higher, while insulin sensitivity indices and total adiponectin were found to be lower in cases, as compared with controls (p < 0.001). Insulin resistance was found to be higher in the admission sample, when compared to the fasting sample in patients with ACS (p = 0.01). On multivariate logistic regression analysis, HOMA-IR and AR index were found to be significantly associated with ACS. AR index was the best independent predictor of ACS, with the highest odds ratio (AR index: adjusted OR 17.528, p < 0.0001 versus HOMA-IR: adjusted OR 1.146, p = 0.001). CONCLUSIONS: The present results implicate that adipokines are significantly associated with pathogenesis of ACS, warranting adequate and early appropriate treatment to reverse this metabolic dysregulation. In our study, AR index was the best predictor of ACS. Hence, the novel AR index might be useful in routine clinical practice for screening persons with increased risk of future development of ACS.

Decrease in left atrium volume after successful balloon mitral valvuloplasty: an echocardiographic and hemodynamic study.

BACKGROUND: Left atrium (LA) remodeling has a crucial adverse impact on outcome and prognosis in mitral stenosis. Few studies have reported the effect of balloon mitral valvuloplasty (BMV) on LA volume. The aim of this study was to assess the evolution of LA volume immediately and 1 month after successful BMV in patients in sinus rhythm. METHODS: Thirty-three consecutive patients (70% women; age 31 ± 8 years; range 19-45) with moderate to severe mitral stenosis (mitral valve area ≤1.5 cm(2) ) who underwent successful BMV were included prospectively. Using two-dimensional echocardiography, and according to the prolate ellipse method, LA volume and LA volume indexed to body surface area were determined before BMV, and 24 hours and 1 month after BMV. Tricuspid and pulmonary regurgitation jets were recorded systematically using continuous-wave Doppler. Pulmonary artery-right ventricular (PA-RV) gradients, reflecting pulmonary pressures, and pulmonary vascular resistance were measured. RESULTS: Mitral valve area increased from 0.88 ± 0.16 to 1.55 ± 0.26 cm(2) (P < 0.0001). Mean mitral valve gradient (MVG) decreased from 16 ± 6 to 6 ± 2 mmHg (P < 0.0001) immediately after BMV. Indexed LA volume fell from 56 ± 14 to 48 ± 12 mL/m(2) (P = 0.0002) immediately after BMV and to 45 ± 13 mL/m(2) at 1 month (P < 0.0001). Only patients with a median LA volume ≥55 mL/m(2) before BMV had a significant reduction in LA volume (P = 0.0001). Decrease in LA volume was correlated with decreases in PA-RV peak diastolic gradient (r = 0.45, P = 0.008) and MVG (r = 0.35, P = 0.04). CONCLUSION: In patients with mitral stenosis in sinus rhythm, successful BMV results in an immediate decrease in LA volume. This reduction, maximal immediately after BMV, correlates with decreases in MVG and PA-RV peak diastolic gradient, and is significant only when LA volume before BMV is severely enlarged.

Pacemaker trouble shooting and follow up.

Pacing system malfunction, although seemingly difficult to assess, can be categorized in relation to the dysfunction of the leads or the generator and apparent dysfunction related to the idiosyncratic characteristics of the pacemaker's timing algorithms. In contrast to the relative frequency of lead failure as a result of implantation error or deterioration of the lead materials, primary malfunction of the pulse generator is rare. Patient-specific problems or inappropriate program settings are relatively common. Consequently, the keys to understanding unexpected pacemaker behavior are meticulous evaluation of the integrity of the leads, assessment of capture and sensing thresholds, and an understanding of the timing cycles of the specific pacemaker, which is facilitated by access to event marker telemetry. Clues to the problem and its cause are founding the patient's history, physical examination, and the various diagnostic tests integral to the pacemaker that are retrieved through bidirectional telemetry. With respect to the hardware, the answer is usually lead dysfunction or a behavioral eccentricity detailed in the pacemaker's technical manual. One must always keep the patient's physiology and pathophysiology in mind, because they also affect the function of the pacing system. Furthermore, even if all components of the system are normal, the pacemaker may be programmed to a set of parameters that are no longer optimal for the patient. When the clinician presented with a suspected pacing system malfunction, it is essential to proceed in a meticulous and orderly manner, carefully assessing, each component of the system, including the pulse generator, the programmed settings, any unique algorithms, the leads, and the patient. If a complete assessment of capture and sensing thresholds, lead impedance, sensor response, and the behavior of any unique algorithms is performed on a periodic basis as part of the routine surveillance of the patient's pacing system, baseline data will be available for comparison with the results of evaluation when and if a problem is suspected.

Polymorphic variants of beta1 adrenergic receptor gene (Ser49Gly & Arg389Gly) in healthy Tamilian volunteers.

BACKGROUND & OBJECTIVES: Several studies reported the polymorphisms of beta1-adrenergic receptor gene in healthy volunteers and its influence on cardiovascular disorders. We investigated the genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism in healthy volunteers of South Indian Tamilian population vis-à-vis other major ethnic groups. METHODS: The genetic variants were determined by using Taqman 5' nuclease assay- real time PCR analysis in 533 normal healthy volunteers (18-60 yr; M=290; F=243). The allelic discrimination analysis was done by 7700 SDS software. RESULTS: The estimated genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared with other major populations. The frequencies of the variant alleles Gly49 and Gly389 were 15.1 and 25.8 per cent respectively. INTERPRETATION & CONCLUSIONS: Our study shows that interethnic variation exists in the polymorphisms of beta1-adrenergic receptor gene and the results generated in this study might serve as a genetic marker for further studies in Tamilian (South India) population.

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk.

BACKGROUND: Essential hypertension is a complex genetic trait. Genetic variant of alpha adducin (ADD1) gene have been implicated as a risk factor for hypertension. Given its clinical significance, we investigated the association between ADD1 Gly460Trp gene polymorphism and essential hypertension in an Indian population. Further, a meta-analysis was carried out to estimate the risk of hypertension. METHODS: In the current study, 432 hypertensive cases and 461 healthy controls were genotyped for the Gly460Trp ADD1 gene polymorphism. Genotyping was determined by real time PCR using Taqman assay. Multiple logistic regression analysis was used to detect the association between Gly460Trp polymorphism and hypertension. RESULTS: No significant association was found in the genotype and allele distribution of Gly460Trp polymorphism with hypertension in our study. A total of 15 case-control studies were included in the meta-analysis. There was no evidence of the association of Gly460Trp polymorphism with hypertension in general or in any of the sub group. CONCLUSIONS: We found that the Gly460Trp polymorphism is not a risk factor for essential hypertension in a south Indian Tamilian population. However, the role of ADD1 polymorphism may not be excluded by a negative association study. Further, large and rigorous case-control studies that investigate gene-gene-environment interactions may generate more conclusive claims about the molecular genetics of hypertension.

Genetic variants of beta(1)-adrenoceptor gene polymorphisms (Ser49Gly and Arg389Gly) and essential hypertension in a south Indian Tamil population.

1. Essential hypertension is a complex polygenic disorder, the pathogenesis of which is dependent on an interplay between genetic and environmental factors. Various studies suggest an association between beta(1)-adrenoceptor gene polymorphisms (Ser49Gly and Arg389Gly) and cardiovascular disorders, including hypertension, cardiomyopathy and congestive heart failure. 2. The genetic profile of the beta(1)-adrenoceptor gene has not yet been documented for any Indian population. Thus, the aim of the present study was to investigate the association between beta(1)-adrenoceptor gene polymorphisms and essential hypertension in a south Indian Tamil population. 3. The present case-control study included 438 patients with essential hypertensives and 444 healthy volunteers from the Tamil population. Genotyping was performed using real-time polymerase chain reaction. 4. Genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared between hypertensive patients and healthy volunteers. The homozygous variant genotype Gly49Gly of the Ser49Gly polymorphism was higher in hypertensive patients compared with controls (12.3 vs 7.4%, respectively). After adjusting for confounding variables (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2-2.9; P < 0.01) by multilogistic regression analysis, the gene was found to be associated with hypertension. A significant interaction was observed in hypertensive patients carrying the Ser49Gly/Gly49Gly x Arg389Gly/Gly389Gly genotypes (OR 1.9; 95% CI 1.1 2.7). 5. In conclusion, the Ser49Gly polymorphism is associated with essential hypertension in a south Indian Tamil population. The results of the present study deviate from those of previous studies, implying that marked interethnic difference exist in beta(1)-adrenoceptor gene polymorphisms.

Lipoprotein (a) and comprehensive lipid tetrad index as a marker for coronary artery disease in NIDDM patients in South India.

BACKGROUND: Coronary artery disease (CAD) is reaching epidemic proportions in India, in the absence of traditional risk factors. Lipoprotein (a) (Lp(a)) concentrations are related to both atherogenesis and thrombogenesis and may be a key link between lipid and CAD. We studied the role of Lp(a) and comprehensive lipid tetrad index as markers for CAD in South Indian patients with non-insulin-dependent diabetes mellitus (NIDDM). METHODS: Lp(a) concentrations and lipid profile were estimated in 53 NIDDM patients with CAD (Group 1), 53 NIDDM patients without CAD (Group 2), and 52 control subjects (Group 3). Comprehensive lipid tetrad index was calculated in all patients and controls. RESULTS: Lp(a) concentrations were significantly higher in Group 1 patients, when compared with Groups 2 and 3. In NIDDM patients with CAD, only total cholesterol and low-density cholesterol concentrations correlated significantly positively with lipoprotein (a) concentrations (r=0.184, p=0.03 and r=0.168, p=0.02). Mean comprehensive lipid tetrad index was 45,487+/-2747 in Group 1, 10,866+/-1163 in Group 2 and 4582+/-348 in Group 3 subjects. CONCLUSION: Based on the foregoing data, high Lp(a) concentrations show strong correlation with CAD in NIDDM patients of South India. High concentrations of Lp(a) and comprehensive lipid tetrad index, along with high prevalence of NIDDM, may render Indians particularly vulnerable to malignant atherosclerosis at a young age. As NIDDM is increasing in prevalence in India, the above observations have ominous dimensions in terms of total burden of CAD in India.

Effect of deep breathing at six breaths per minute on the frequency of premature ventricular complexes.

Although the effect of reflex increase in vagal tone on the frequency of premature ventricular complexes (PVC) is known, the effect of timed deep breathing on the frequency of PVC has not been reported. We serendipitously discovered that deep breathing at six breaths per minute abolished PVC in an 18-year-old female with frequent PVC, anxiety, and palpitations. In five of a series of 10 consecutive patients with frequent (> or = 10/min) unifocal PVC, deep breathing at 6 breaths/min reduced the frequency of PVC by at least 50%. This is possibly due to increased vagal modulation of sinoatrial and atrioventricular node. However, factors predicting the response to deep breathing, and the mechanisms involved need to be studied in a larger number of patients.

Association of sympathovagal imbalance with obesity indices, and abnormal metabolic biomarkers and cardiovascular parameters.

PROBLEM: Pathophysiological mechanisms contributing to abnormal cardiovascular (CV) parameters in obesity have not been fully elucidated. Role of sympathovagal imbalance (SVI) in the prediction of abnormalities in CV functions in obesity has not been studied. METHODS: Anthropometric indices, CV parameters, autonomic function tests (AFTs) such as spectral heart rate variability (HRV) analysis, heart rate and blood pressure response to standing, deep breathing, and isometric-handgrip, and biochemical parameters like insulin resistance (HOMA-IR), lipid risk factors and inflammatory marker [high-sensitive C-reactive protein (hsCRP)] were assessed in control group (non-obese, n=43) and obese group (n=45). Association of anthropometric indices and abnormal CV parameters with low-frequency to high-frequency ratio (LF-HF) of HRV was performed by Pearson's correlation. Independent contribution of anthropometric indices and abnormal CV parameters to LF-HF was assessed by using a multiple regression analysis. LF-HF prediction of rate-pressure product (RPP), the indicator of CV dysfunction was assessed by logistic regression. RESULTS: LF-HF, the marker of SVI was more in obese group compared to control group. AFTs of sympathetic activity were increased and of parasympathetic activity were reduced in obese group. Anthropometric indices, HOMA-IR, lipid risk factors and hsCRP were correlated with LF-HF. These metabolic biomarkers had independent contribution to SVI. Among, anthropometric indices, waist-to-height ratio (WHtR) had maximum association with LF-HF. LF-HF had significant prediction of RPP in obese group. CONCLUSION: SVI in obesity is due to both increased sympathetic and decreased vagal activity. Abnormal CV parameters in obesity are linked to SVI, which is contributed by insulin resistance, dyslipidaemia and low-grade inflammation. LF-HF predicts abnormal CV parameters in obesity.

Sinus node function after autonomic blockade in normals and in sick sinus syndrome.

Electrophysiologic studies were performed in 10 normals and 33 patients with sick sinus syndrome before and after total autonomic blockade with propranolol and atropine. In normals both corrected sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) decreased significantly after autonomic blockade. In patients with sick sinus syndrome the corrected SNRT was abnormal (greater than 450 msec) in 16 (48.5%) cases before and 25 (76%) cases (greater than 285 msec) after autonomic ablation (P less than 0.02). Thirteen of 21 patients (62%) with normal intrinsic heart rate and all 12 cases with abnormally low intrinsic rate after autonomic blockade had abnormal corrected SNRT (greater than 285 msec). Mean SACT measured in 19 patients also shortened significantly following pharmacologic denervation. During control it was prolonged (greater than 226 msec) in 8 patients (44%). After autonomic blockade 2 of 13 patients with normal intrinsic heart rate and 3 of 6 with low intrinsic rate showed abnormal SACT (greater than 151 msec). The data suggest that the majority (76%) of patients with sick sinus syndrome have intrinsic abnormality of sinus node automaticity while in a minority (24%) disturbed autonomic regulation is the pathogenetic mechanism. Patients with normal intrinsic heart rate usually have normal intrinsic SACT, while a significant proportion of those with low intrinsic rate have abnormal perinodal conduction. Subjects with abnormal intrinsic heart rate have more severe disturbances of sinus node function than those with normal intrinsic rate.

A comparative evaluation of metoprolol and methyldopa in the management of pregnancy induced hypertension.

Thirty patients matched for age, parity, socioeconomic status and severity of pregnancy induced hypertension (PIH) were randomly allocated to treatment with metoprolol or methyldopa. The average fall in diastolic blood pressure was significant in the group treated with metoprolol as compared with the methyldopa group (p less than 0.01). There were 3 perinatal deaths in the methyldopa group and 1 in the metoprolol group; the mean birth weight of the babies was higher in cases treated with metoprolol. The results suggest metoprolol to be more efficacious with regard to control of hypertension and fetal outcome in cases of pregnancy induced hypertension.

Supravalvular aortic stenosis and coronary ostial stenosis in homozygous familial hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia exhibit severe hypercholesterolemia, cutaneous and tendon xanthomata, and premature atherosclerosis from childhood. A rare presentation of this condition with supravalvular aortic stenosis and coronary ostial stenosis is described.

Prevalence of left atrial thrombus in rheumatic mitral stenosis with atrial fibrillation and its response to anticoagulation: a transesophageal echocardiographic study.

BACKGROUND: The frequency of occurrence of left atrial thrombi, and the effect of anticoagulation in patients with rheumatic mitral stenosis and atrial fibrillation is not well established. This study was conducted to evaluate the occurrence of left atrial body and left atrial appendage clots in patients with rheumatic mitral stenosis and atrial fibrillation, and to document the effect of long-term anticoagulation on clot dissolution. METHODS AND RESULTS: Consecutive patients with severe rheumatic mitral stenosis and atrial fibrillation were assessed by transesophageal echocardiography. Those with left atrial body or left atrial appendage clots were anticoagulated with oral nicoumalone. Transesophageal echocardiography was then repeated in patients on anticoagulation who were on regular follow-up, and in whom percutaneous transvenous mitral commissurotomy could be considered. Of the 490 patients studied, 163 had left atrial body or left atrial appendage clots. A repeat transesophageal echocardiographic examination was done in 50 patients who had optimal anticoagulation for a period of 6 months. Only 2 of the 17 patients who had left atrial body clots had successful clot dissolution after long-term anticoagulation, while the left atrial appendage clots disappeared in 31 of 33 patients (p<0.001). CONCLUSIONS: Left atrial clots are present in a third of patients with severe rheumatic mitral stenosis and atrial fibrillation. Isolated left atrial appendage clots in patients with rheumatic mitral stenosis and atrial fibrillation can disappear with long-term anticoagulation, while thrombi that extend into the left atrial body may persist despite optimal anticoagulation.

Angioplasty of membranous obstruction of inferior vena cava.

Membranous obstruction of vena cava (MOVC) is a common cause of hepatic venous outflow obstruction. Surgical procedures utilized to relieve symptoms carry a high morbidity and mortality. A patient who presented with gradual onset ascites and dilated, tortuous veins over the anterior abdominal wall and the back was found to have MOVC by inferior vena cavogram. Balloon dilatation of the obstruction was done successfully through a transvenous approach. Following this, the patient improved remarkably. The procedure is safe, effective and easy to perform. This balloon angioplasty provides alternative method for treatment of membranous obstruction of vena cava.

Sensory nerve conduction in diabetes mellitus and diabetic neuropathy.

Electrophysiological evaluation of conduction in sensory fibres of right ulnar and median nerves were carried out in normal subjects and diabetics with and without neuropathy. The sensory conduction velocities of ulnar as well as median nerves are significantly depressed in both groups of diabetics, particularly in those with neuropathy. The diabetics with or without neuropathy require a higher strength of stimulus for conduction in both median and ulnar nerves as compared to the normal subjects. The amplitude of action potentials is also lowered in both ulnar and median nerves of the two groups of diabetics. Estimation of conduction velocities of sensory fibres can be considered as a more useful parameter than the measurement of amplitude of action potentials in the diagnosis and evaluation of neuropathy in diabetics. It is concluded that assessment of sensory nerve conduction in median nerve is a better indicator than that of ulnar nerve for this purpose.

Lipoprotein ratios as surrogate markers for insulin resistance in South indians with normoglycemic nondiabetic acute coronary syndrome.

Background. Insulin resistance has been associated with dyslipidemia and cardiovascular disease. Even though homeostasis model assessment of insulin resistance (HOMA-IR) is a well-known insulin resistance predictor, estimation of serum lipoprotein ratios has been recently suggested as a surrogate marker for insulin resistance. Here, we evaluated the relationship between lipoprotein ratios and insulin resistance in normoglycemic nondiabetic south Indians with acute coronary syndrome. Methods. 100 normoglycemic nondiabetic ACS patients and 140 controls were enrolled in the study. Levels of fasting glucose, fasting insulin, and lipid profile [total cholesterol (TC), triglycerides (TG), and high density lipoprotein cholesterol (HDL-C)], lipoprotein(a) [Lp(a)] levels were measured and lipoprotein ratios were computed. HOMA-IR was used to calculate the insulin resistance. Receiver operating characteristic curves (ROC) analysis was used to compare the power of these lipoprotein ratios to predict insulin resistance. Results. Lipoprotein ratios were significantly higher in normoglycemic nondiabetic ACS patients, as compared to healthy controls, and were significantly correlated with HOMA-IR by Spearman's rank correlation analysis. ROC curve showed that Lp(a)/HDL-C and TG/HDL-C ratios were the best surrogate predictors of insulin resistance in normoglycemic nondiabetic ACS. Conclusion. This study demonstrates that serum lipoprotein ratios significantly correlate with insulin resistance in normoglycemic nondiabetic ACS. Lp(a)/HDL-C and TG/HDL-C ratios could be used as surrogate markers of insulin resistance in atherosclerosis-prone south Indians with normoglycemic nondiabetic ACS.

A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure.

AIMS: The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). METHODS: 130 patients were recruited and randomized into two groups: Control Group (CG) (n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. RESULT: Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). CONCLUSION: These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.