ABSTRACT
Malignant coronary artery disease (CAD) refers to a severe and extensive atherosclerotic process involving multiple coronary arteries in young individuals (aged <45 years in men and <50 years in women) with a low or no burden of established risk factors. Indians, in general, develop acute myocardial infarction (AMI) about 10 years earlier; AMI rates are threefold to fivefold higher in young Indians than in other populations. Although established CAD risk factors have a predictive value, they do not fully account for the excessive burden of CAD in young Indians. Lipoprotein(a) (Lp(a)) is increasingly recognized as the strongest known genetic risk factor for premature CAD, with high levels observed in Indians with malignant CAD. High Lp(a) levels confer a twofold to threefold risk of CAD—a risk similar to that of established risk factors, including diabetes. South Asians have the second highest Lp(a) levels and the highest risk of AMI from the elevated levels, more than double the risk observed in people of European descent. Approximately 25% of Indians and other South Asians have elevated Lp(a) levels (≥50 mg/dl), rendering Lp(a) a risk factor of great importance, similar to or surpassing diabetes. Lp(a) measurement is ready for clinical use and should be an essential part of all CAD research in Indians.
ABSTRACT
Lipoprotein(a) [Lp(a)] is a circulating lipoprotein, and its level is largely determined by variation in the Lp(a) gene (LPA) locus encoding apo(a). Genetic variation in the LPA gene that increases Lp(a) level also increases coronary artery disease (CAD) risk, suggesting that Lp(a) is a causal factor for CAD risk. Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), a proatherogenic and proinflammatory biomarker. Lp(a) adversely affects endothelial function, inflammation, oxidative stress, fibrinolysis, and plaque stability, leading to accelerated atherothrombosis and premature CAD. The INTER-HEART Study has established the usefulness of Lp(a) in assessing the risk of acute myocardial infarction in ethnically diverse populations with South Asians having the highest risk and population attributable risk. The 2018 Cholesterol Clinical Practice Guideline have recognized elevated Lp(a) as an atherosclerotic cardiovascular disease risk enhancer for initiating or intensifying statin therapy.
ABSTRACT
Rheumatic heart disease continues to be a major health problem in many parts of the world. The epidemiology of rheumatic heart disease in India is of special interest as it may help to understand the effects of economic transition on this enigmatic disease. Critical appraisal of the published literature suggests the possibility of a real decline in the occurrence of the disease in some parts of the country, but a continuing onslaught in several other regions. The rate of decline seems to correlate more with improved public health facilities than with economic development alone. However, the cumulative burden of the disease remains high, and sustained efforts for the prevention of rheumatic heart disease are warranted.
Subject(s)
Cost of Illness , Humans , India/epidemiology , Prevalence , Rheumatic Heart Disease/epidemiology , Time FactorsABSTRACT
BACKGROUND: The purpose of this study was to prospectively evaluate a large group of consecutive, non-anticoagulated patients with severe rheumatic mitral stenosis and to analyze the left atrial appendage function in relation to left atrial appendage clot and spontaneous echo contrast formation. METHODS AND RESULTS: We prospectively studied left atrial appendage function in 200 consecutive patients with severe mitral stenosis who underwent transesophageal echocardiography and correlated it with spontaneous echo contrast and left atrial appendage clot. The mean age was 30.2 +/- 9.4 years. Fifty-five (27.5%) patients were in atrial fibrillation. Left atrial appendage clot was present in 50 (25%) patients and 113 (56.5%) had spontaneous echo contrast. The older age, increased duration of symptoms, atrial fibrillation, spontaneous echo contrast, larger left atrium, depressed left atrial appendage function and type II and III left atrial appendage flow patterns correlated significantly (p<0.05) with the left atrial appendage clot. Left atrial appendage ejection fraction was significantly less in patients with clot (21.8 +/- 12.8% v. 39.1 +/- 13.2%, p<0.0001) and in those with spontaneous echo contrast (30.3 +/- 16.2 % v. 40.3 +/- 11.8%, p<0.001). Left atrial appendage filling (18.0 +/- 11.7 v. 27.6 +/- 11.8 cm/s, p <0.0001) and emptying velocities (15.4 +/- 7.0 v. 21.5 +/- 9.6 cm/s, p<0.001) and filling (1.4 +/- 1.0 v. 2.5 +/- 1.4 cm, p<0.0001) and emptying (1.5 +/- 1.2 v. 2.1 +/- 1.2 cm, p <0.05) velocity time integrals were also significantly lower in patients with clot as compared to those without clot. On multivariate regression analysis, atrial fibrillation (odds ratio 6.68, 95% CI 1.85-24.19, p=0.003) and left atrial appendage ejection fraction (odds ratio 1.06, 95% CI 1.00 - 1.11, p=0.04) were the only two independent predictors of clot formation. Incidence of clot was 62.59% in patients with left atrial appendage ejection fraction < or = 25% as compared to 10.4% in those having left atrial appendage ejection fraction >25%. Similarly patients with spontaneous echo contrasthadlower filling (21.7 +/- 11.5 v. 29.4 +/- 12.7 cm/s, p<0.0001) and emptying (17.0 +/- 8.1 v. 23.9 +/- 10.9 cm/s, p<0.0001) velocities, as well as filling (1.9 +/- 1.3 v. 2.7 +/- 1.3 cm, p<0.01) and emptying (1.7 +/- 1.0 v. 2.3 +/- 1.4 cm, p<0.01) velocity time integrals as compared to patients without spontaneous echo contrast. In a subgroup of the patients with normal sinus rhythm, the left atrial appendage ejection fraction was significantly less in patients with clot compared to those without clot (31.2 +/- 13.2 v. 41.3 +/- 11.5 %, p<0.01). CONCLUSIONS: In the patients with severe mitral stenosis, besides atrial fibrillation, a subgroup of patients in normal sinus rhythm with depressed left atrial appendage function (left atrial appendage ejection fraction < or = 25%) had a higher risk of clot formation in left atrial appendage and these patients should be routinely anticoagulated for prevention of clot formation.