Sex Disparities in the Treatment and Control of Cardiovascular Risk Factors in Type 2 Diabetes

OBJECTIVE—To assess whether sex differences exist in the effective control and medication treatment intensity of cardiovascular disease (CVD) risk factors

Association between the Interleukin-6 Promoter Polymorphism −174G/C and Serum Lipoprotein(a) Concentrations in Humans

Background: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease. The interleukin-6 (IL-6) receptor antagonist tocilizumab has been shown to lower serum Lp(a) concentrations. We investigated whether the IL-6 single nucleotide polymorphism 2174G/C is associated with baseline serum Lp(a) concentrations. Methodology/Principal Findings: We divided 2321 subjects from the Lipid Analytic Cologne (LIANCO) cohort into 2 groups, the ones with substantially elevated Lp(a), defined as concentrations $60 mg/dl (n = 510), and the ones with Lp(a),60 mg/ dl (n = 1811). The association with the genotypes GG (33.7%), GC (50.75%) and CC (15.55%) was investigated. The GC and the CC genotype were associated with a significantly increased odds ratio of having substantially elevated Lp(a) concentrations (OR = 1.3, 95 % CI 1.04 to 1.63, P = 0.02 and OR = 1.44, 95 % CI 1.06 to 1.93, P = 0.018). These associations remained significant after adjusting for age, sex, smoking behavior, body mass index, serum lipoproteins, hypertension and diabetes. Of these covariates, only LDL cholesterol was significantly and independently associated with elevated Lp(a) concentrations. Conclusions/Significance: The IL-6 single nucleotide polymorphism 2174G/C is associated with increased odds of having elevated Lp(a). Whether this association plays a role in the Lp(a)-lowering effects of IL-6 receptor antagonists remains to b

The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population

Background: The PCK1 gene, encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), has previously been implicated as a candidate gene for type 2 diabetes (T2D) susceptibility. Rodent models demonstrate that over-expression of Pck1 can result in T2D development and a single nucleotide polymorphism (SNP) in the promoter region of human PCK1 (-232C/G) has exhibited significant association with the disease in several cohorts. Within the UK-resident South Asian population, T2D is 4 to 6 times more common than in indigenous white Caucasians. Despite this, few studies have reported on the genetic susceptibility to T2D in this ethnic group and none of these has investigated the possible effect of PCK1 variants. We therefore aimed to investigate the association between common variants of the PCK1 gene and T2D in a UK-resident South Asian population of Punjabi ancestry, originating predominantly from the Mirpur area of Azad Kashmir, Pakistan. \ud \ud Methods: We used TaqMan assays to genotype five tagSNPs covering the PCK1 gene, including the -232C/G variant, in 903 subjects with T2D and 471 normoglycaemic controls. \ud \ud Results: Of the variants studied, only the minor allele (G) of the -232C/G SNP demonstrated a significant association with T2D, displaying an OR of 1.21 (95% CI: 1.03 - 1.42, p = 0.019). \ud \ud Conclusion: This study is the first to investigate the association between variants of the PCK1 gene and T2D in South Asians. Our results suggest that the -232C/G promoter polymorphism confers susceptibility to T2D in this ethnic group. \ud \ud Trial registration: UKADS Trial Registration: ISRCTN38297969

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP)

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety

Lipoprotein(a) and inflammation in patients with atrial fibrillation after electrical cardioversion

<p>Abstract</p> <p>Background</p> <p>Recently few studies tried to confirm the association between AF and lipoprotein(a) (Lp(a)), however the results remained conflicted. In present study we evaluated the possible interaction between Lp(a), inflammatory state and echocardiographic characteristics in patients after successful electrical cardioversion (EC) of persistent AF. We also tried to investigate the role of Lp(a) as a possible prognostic factor for AF recurrence after successful EC.</p> <p>Results</p> <p>Data of 79 patients admitted due to planned EC was analyzed. After successful procedure patients were monitored for 2 years. For analytical purposes patients were divided in two groups according to AF recurrence. There was no significant difference between Lp(a) levels in both groups. We also didn't find any positive correlation between Lp(a) and CRP levels, as well as between Lp(a) levels and left atrium diameter. For logistic and survival analysis optimal cut-off value of Lp(a) ≥ 0.32 (upper quartile) was used. In logistic regression model with AF recurrence as dependent variable Lp(a) didn't show any statistically significant association with AF recurrence. Survival analysis showed slightly higher AF recurrence rate in group with higher Lp(a) levels but not to the level of statistical significance (log rank test, <it>p </it>= 0.62).</p> <p>Conclusions</p> <p>We weren't able to confirm the association between Lp(a) levels and AF recurrence, inflammation and left atrium diameter in patients after successful EC of persistent AF. Further studies are needed to elucidate the role of Lp(a) in this clinical setting.</p

A Retrospective Cohort Study of the Potency of lipid-lowering therapy and Race-gender Differences in LDL cholesterol control

<p>Abstract</p> <p>Background</p> <p>Reasons for race and gender differences in controlling elevated low density lipoprotein (LDL) cholesterol may be related to variations in prescribed lipid-lowering therapy. We examined the effect of lipid-lowering drug treatment and potency on time until LDL control for black and white women and men with a baseline elevated LDL.</p> <p>Methods</p> <p>We studied 3,484 older hypertensive patients with dyslipidemia in 6 primary care practices over a 4-year timeframe. Potency of lipid-lowering drugs calculated for each treated day and summed to assess total potency for at least 6 and up to 24 months. Cox models of time to LDL control within two years and logistic regression models of control within 6 months by race-gender adjust for: demographics, clinical, health care delivery, primary/specialty care, LDL measurement, and drug potency.</p> <p>Results</p> <p>Time to LDL control decreased as lipid-lowering drug potency increased (P < 0.001). Black women (N = 1,440) received the highest potency therapy (P < 0.001) yet were less likely to achieve LDL control than white men (N = 717) (fully adjusted hazard ratio [HR] 0.66 [95% CI 0.56-0.78]). Black men (N = 666) and white women (N = 661) also had lower adjusted HRs of LDL control (0.82 [95% CI 0.69, 0.98] and 0.75 [95% CI 0.64-0.88], respectively) than white men. Logistic regression models of LDL control by 6 months and other sensitivity models affirmed these results.</p> <p>Conclusions</p> <p>Black women and, to a lesser extent, black men and white women were less likely to achieve LDL control than white men after accounting for lipid-lowering drug potency as well as diverse patient and provider factors. Future work should focus on the contributions of medication adherence and response to treatment to these clinically important differences.</p

Excess cardiovascular risk in diabetic women: a case for intensive treatment.

Diabetes is a common and rapidly growing disease that affects more than 380 million people worldwide and is an established risk factor for cardiovascular disease with differential effects on women compared to men. While the general population of women, particularly young women, has more favourable cardiovascular risk profiles than men, this protective effect has been shown to be lost or even reversed in diabetic women. Several studies have demonstrated a significant diabetes-associated excess risk of cardiovascular disease in women. Sex-specific differences in risk factors associated with diabetes and their management may be responsible for the relative excess cardiovascular risk in women with diabetes. Diabetic women need intensive treatment in order to optimize management of cardiovascular risk factors. Further studies are needed to elucidate the mechanisms underlying the excess cardiovascular risk in diabetic women in order to tailor prevention and treatment strategies

An Updated Meta-Analysis of Endothelial Nitric Oxide Synthase Gene: Three Well-Characterized Polymorphisms with Hypertension

BACKGROUND: Numerous individually underpowered association studies have been conducted on endothelial nitric oxide synthase (eNOS) genetic variants across different ethnic populations, however, the results are often irreproducible. We therefore aimed to meta-analyze three eNOS widely-evaluated polymorphisms, G894T (rs1799983) in exon 7, 4b/a in intron 4, and T-786C (rs2070744) in promoter region, in association with hypertension from both English and Chinese publications, while addressing between-study heterogeneity and publication bias. METHODS: Data were analyzed using Stata software (version 11.0), and random-effects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Publication bias was weighed using the Egger's test and funnel plot. RESULTS: There were total 19284/26003 cases/controls for G894T, and 6890/6858 for 4b/a, and 5346/6392 for T-786C polymorphism. Overall comparison of allele 894T with 894G in all study populations yielded a 16% increased risk for hypertension (odds ratio [OR] = 1.16; 95% confidence interval [95% CI]: 1.07-1.27; P = 0.001), and particularly a 32% increased risk (95% CI: 1.16-1.52; P<0.0005) in Asians and a 40% increased risk (95% CI: 1.19-1.65; P<0.0005) in Chinese. Further subgroup analyses suggested that published languages accounted for the heterogeneity for G894T polymorphism. The overall OR of allele 4a versus 4b was 1.29 (95% CI: 1.13-1.46; P<0.0005) in all study populations, and this estimate was potentiated in Asians (OR = 1.42; 95% CI: 1.16-1.72; P<0.0005). For T-786C, ethnicity-stratified analyses suggested a significantly increased risk for -786C allele (OR = 1.25; 95% CI: 1.06-1.47; P = 0.007) and -786CC genotype (OR = 1.69; 95% CI: 1.20-2.38; P = 0.003) in Whites. As an aside, the aforementioned risk estimates reached significance after Bonferroni correction. Finally, meta-regression analysis on other study-level covariates failed to provide any significance for all polymorphisms. CONCLUSION: We, via a comprehensive meta-analysis, ascertained the role of eNOS G894T and 4b/a polymorphisms on hypertension in Asians, and T-786C polymorphism in Whites