Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

Introduction: The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males. Aim: We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD). Methods: We compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls. Results: The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p ¼0.007 and OR 2.39; p ¼0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p ¼0.047 and OR 2.26; p ¼0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p ¼0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p ¼0.018) were independent predictors of development of PH in females.

Treatment of Hypercholesterolaemia in Patients with Diabetes Mellitus

Numerous studies have shown that statins reduce cardiovascular events; including stroke and mortality in diabetics. The American Diabetes Association 2013 guidelines recommend that diabetics at high risk for cardiovascular events should have their serum low-density lipoprotein (LDL) cholesterol reduced to 70 mg/dl (1.8 mmol/l) with statins. Lower-risk diabetics should have their serum LDL cholesterol reduced to 100 mg/dl (2.6 mmol/l). The 2013 American College of Cardiology/American Heart Association lipid guidelines recommend giving high-dose statins to adult diabetics aged ? 75 years with atherosclerotic vascular disease (ASCVD) unless contraindicated with a class I indication and moderate-dose or high-dose statins to diabetics with ASCVD ? 75 years with a class IIa indication. Diabetics ? 21 years with a serum LDL cholesterol of ? 190 mg/dl (4.9 mmol/l) should be treated with high-dose statins with a class I indication. For primary prevention in diabetics aged 40 to 75 years and serum LDL cholesterol between 70 and 189 mg/dl (1.8 and 4.9 mmol/l); moderate-dose statins should be given with a class I indication. For primary prevention in diabetics aged 40 to 75 years; a serum LDL cholesterol between 70 and189 mg/dl (1.8 and 4.9 mmol/l); and a 10-year risk of ASCVD of ? 7.5 calculated from the Pooled Heart Equation; high-dose statins should be given with a class IIa indication. For primary prevention in diabetics aged 21 to 39 years or older than 75 years and a serum LDL cholesterol between 70 and 189 mg/dl (1.8 and 4.9 mmol/l); moderate-dose statins or high-dose statins should be given with a class IIa indication. There is no additional ASCVD reduction from adding non-statin therapy to further lower non-high-density lipoprotein (HDL) cholesterol once an LDL cholesterol goal has been reached. Clinical trials have found no lowering of cardiovascular events or mortality in diabetics treated with statins with the addition of nicotinic acid; fibric acid derivatives; ezetemibe; or drugs that raise serum HDL cholesterol

Hyponatremia and cerebrovascular spasm in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Hyponatremia develops in approximately a third of patients with aneurysmal subarachnoid hemorrhage (SAH). Studies have been conflicting about the association between hyponatremia and cerebrovascular spasm (CVS). AIMS: To investigate whether hyponatremia can signal the onset of CVS. SETTINGS AND DESIGN: Retrospective chart review of all patients with SAH treated at a tertiary-care university hospital from January to May 2002. MATERIALS AND METHODS: 106 patients were included in the study. Serum sodium levels were recorded from days 1 to 14 of hospitalization. Hyponatremia was defined as serum sodium level<135 meq/l and a fall in sodium level of >4 meq/l from the admission sodium level. The presence of CVS was determined by transcranial doppler sonography. Patients were assigned to one of four groups based on the presence or absence of CVS and hyponatremia. STATISTICAL ANALYSIS: Student's t-test was used for comparison of means. A logistical regression model was constructed and odds ratios (OR) were calculated. RESULTS: 41 patients developed hyponatremia and 44 developed CVS. Among the 41 with hyponatremia, 22 (54%) had evidence of CVS, whereas among the 65 patients without hyponatremia, 22 (34%) had evidence of CVS (P=0.023). Among those with hyponatremia, the mean sodium drop was 7.9 meq/L in those with CVS compared to 7.0 meq/L in those without CVS (P=0.068). More than half of those with hyponatremia and CVS (13/22) developed hyponatremia at least a day before CVS was diagnosed. CONCLUSION: In patients with SAH, hyponatremia is associated with a significantly greater risk of developing CVS and may precede CVS by at least one day.