Leptin and adiponectin in relation to body fat percentage, waist to hip ratio and the apoB/apoA1 ratio in Asian Indian and Caucasian men and women

BACKGROUND: Asian Indian immigrants have an increased risk for developing cardiovascular disease (CVD); however, there is very little data examining how the adipokines leptin and adiponectin relate to CVD risk factors such as body fat percentage (BF%), waist to hip ratio (WHR) and the apoB/apoA1 ratio in Asian Indian men and women living in Canada. SUBJECTS AND METHODS: A cross-sectional study comparing leptin, adiponectin, lipoproteins and anthropometric parameters in Asian Indian men and women to Caucasian men and women (4 groups). Anthropometric data (BMI, BF%, WHR), circulating lipids (apoA1, apoB, total cholesterol, and HDL-cholesterol), leptin and adiponectin were measured. RESULTS: Asian Indian men and women had higher leptin and lower adiponectin concentrations then Caucasian men and women, respectively. Leptin (positively) and adiponectin (negatively) correlated with anthropometric parameters and lipoproteins in all four groups. Using stepwise forward multiple regression, a model including TC/HDL-C ratio, WHR, BF%, hip circumference and waist circumference predicted 74.2% of leptin concentration in men. In women, apoB, BF%, waist circumference and age predicted 77.5% of leptin concentration. Adiponectin concentrations in men were predicted (30.2%) by HDL-C, total cholesterol, hip circumference and BF% while in women 41.2% of adiponectin concentration was predicted by the apoB/apoA1 ratio, WHR and age. CONCLUSION: As is evident from our data, there is a strong relationship between leptin, adiponectin, and abdominal obesity with increased CVD risk, as assessed by the apoB/apoA1 ratio. Dysregulation of these parameters may account for the increased risk of CVD in Asian Indians

The causal exposure model of vascular disease

Primary prevention of cardiovascular disease is governed at present by the risk factor model for cardiovascular events, a model which is widely accepted by physicians and professional associations, but which has important limitations: most critically, that effective treatment to reduce arterial damage is often delayed until the age at which cardiovascular events become common. This delay means that many of the early victims of vascular disease will not be identified in time. This delay also allows atherosclerosis to develop and progress unchecked within the arterial tree with the result that the absolute effectiveness of preventive therapy is limited by the time it is eventually initiated. The causal exposure model of vascular disease is an alternative to the risk factor model for cardiovascular events. Whereas the risk factor model aims to identify and treat those at markedly increased risk of vascular events within the next decade, the causal exposure model of vascular disease aims to prevent events by treating the causes of the disease when they are identified. In the risk factor model, age is an independent non-modifiable risk factor and the predictive power of age far outweighs that of the other risk factors. In the causal exposure model, age is the duration of time the arterial wall is exposed to the causes of atherosclerosis: apoB (apolipoprotein B) lipoproteins, hypertension, diabetes and smoking. Preventing the development of advanced atherosclerotic lesions by treating the causes of vascular disease is the simplest, surest and most effective way to prevent clinical events

Diabetes, Abdominal Adiposity, and Atherogenic Dyslipoproteinemia in Women Compared With Men

OBJECTIVE—To understand why atherogenic risk differs more between diabetic and nondiabetic women than between diabetic and nondiabetic men

Regulation of plasma LDL: the apoB paradigm

The objectives of this analysis are to re-examine the foundational studies of the in vivo metabolism of plasma LDL (low-density lipoprotein) particles in humans and, based on them, to reconstruct our understanding of the governance of the concentration of plasma LDL and the maintenance of cholesterol homoeostasis in the hepatocyte. We believe that regulation of cholesterol homoeostasis within the hepatocyte is demonstrably more complex than envisioned by the LDL receptor paradigm, the conventional model to explain the regulation of plasma LDL and the fluxes of cholesterol into the liver, a model which was generated in the fibroblast but has never been fully validated in the hepatocyte. We suggest that the LDL receptor paradigm should be reconfigured as the apoB (apolipoprotein B) paradigm, which states that the rate at which LDL particles are produced is at least an important determinant of their concentration in plasma as the rate at which they are cleared from plasma and that secretion of cholesterol within VLDL (very-low-density lipoprotein) particles is an important mechanism of maintaining cholesterol homoeostasis within the hepatocyte. These two paradigms are not mutually exclusive. The LDL receptor paradigm, however, includes only one critical aspect of the regulation of plasma LDL, namely the rate at which LDL particles are cleared through the LDL receptor pathway, but ignores another – the rate at which LDL particles are added to the plasma compartment. The apoB paradigm includes both and points to a different model of how the hepatocyte achieves cholesterol homoeostasis in a complex metabolic environment

Diabetes, Abdominal Adiposity, and Atherogenic Dyslipoproteinemia in Women Compared With Men

OBJECTIVE—To understand why atherogenic risk differs more between diabetic and nondiabetic women than between diabetic and nondiabetic men

Relations of Change in Plasma Levels of LDL‐C, Non‐HDL‐C and apoB With Risk Reduction From Statin Therapy: A Meta‐Analysis of Randomized Trials

Background: Identifying the best markers to judge the adequacy of lipid‐lowering treatment is increasingly important for coronary heart disease (CHD) prevention given that several novel, potent lipid‐lowering therapies are in development. Reductions in LDL‐C, non‐HDL‐C, or apoB can all be used but which most closely relates to benefit, as defined by the reduction in events on statin treatment, is not established. Methods and Results: We performed a random‐effects frequentist and Bayesian meta‐analysis of 7 placebo‐controlled statin trials in which LDL‐C, non‐HDL‐C, and apoB values were available at baseline and at 1‐year follow‐up. Summary level data for change in LDL‐C, non‐HDL‐C, and apoB were related to the relative risk reduction from statin therapy in each trial. In frequentist meta‐analyses, the mean CHD risk reduction (95% CI) per standard deviation decrease in each marker across these 7 trials were 20.1% (15.6%, 24.3%) for LDL‐C; 20.0% (15.2%, 24.7%) for non‐HDL‐C; and 24.4% (19.2%, 29.2%) for apoB. Compared within each trial, risk reduction per change in apoB averaged 21.6% (12.0%, 31.2%) greater than changes in LDL‐C (P<0.001) and 24.3% (22.4%, 26.2%) greater than changes in non‐HDL‐C (P<0.001). Similarly, in Bayesian meta‐analyses using various prior distributions, Bayes factors (BFs) favored reduction in apoB as more closely related to risk reduction from statins compared with LDL‐C or non‐HDL‐C (BFs ranging from 484 to 2380). Conclusions: Using both a frequentist and Bayesian approach, relative risk reduction across 7 major placebo‐controlled statin trials was more closely related to reductions in apoB than to reductions in either non‐HDL‐C or LDL‐C

Evaluation of the pleiotropic effects of statins:a reanalysis of the randomized trial evidence using Egger regression

Objective— To reanalyze data from recent randomized trials of statins to assess whether the benefits and risks of statins are mediated primarily via their LDL-C (low-density lipoprotein cholesterol) lowering effects or via other mechanisms. Approach and Results— We adapted Egger regression, a technique frequently used in Mendelian randomization studies to detect genetic pleiotropy, to reanalyze the available randomized control trial data of statin therapy. For cardiovascular end points, each 1 mmol/L change in LDL-C with statin therapy was associated with a hazard ratio of 0.77 (95% confidence interval, 0.71–0.84) with an intercept that was indistinguishable from zero (intercept, −0.0032; [95% confidence interval, −0.090 to 0.084]; P =0.94), indicating no pleiotropy. For incident diabetes mellitus, a 1 mmol/L change in LDL-C with statin therapy was associated with a hazard ratio of 1.07 (95% confidence interval, 0.99–1.16) and an intercept nondistinguishable from zero (intercept, −0.015; [95% confidence interval, −0.30 to 0.27]; P =0.91), again indicating no pleiotropy. Conclusions— Our reanalysis of the randomized control trial data using Egger regression adds to the existing evidence that the cardiovascular benefits of statins and their association with incident diabetes mellitus are mediated primarily, if not entirely, via their LDL-C lowering properties rather than by any pleiotropic effects. </jats:sec