Dietary and Genetic Probes of Atherogenic Dyslipidemia

Abstract

Abstract-A goal of dietary management of cardiovascular disease risk in patients with obesity and metabolic syndrome is improvement in the atherogenic dyslipidemia comprising elevated triglyceride, reduced high-density lipoprotein (HDL) cholesterol, and increased numbers of small, dense low-density lipoprotein (LDL) particles. Individuals with a genetically influenced trait characterized by a high proportion of small, dense LDL (phenotype B) respond to a low-fat, high-carbohydrate diet with greater reduction of LDL cholesterol, apoprotein B, and mid-sized LDL2 particles than unaffected subjects (phenotype A). In contrast, in phenotype A subjects there is a reciprocal shift from large LDL1 to small LDL3 such that a high proportion convert to phenotype B. There is evidence for heritable effects on these diet-induced subclass changes and for the involvement of specific genes. For example, a haplotype of the APOA5 gene associated with increased plasma triglyceride and small, dense LDL predicts greater diet-induced reduction of LDL2, a haplotype-specific effect that is strongly correlated with both increased VLDL precursors and LDL4 products. Understanding of such diet-genotype interactions may help to elucidate mechanisms that are responsible for phenotype B and for its differential dietary responsiveness. This information may also ultimately help in identifying those individuals who are most likely to achieve cardiovascular risk benefit from specific dietary interventions. Key Words: lipoproteins Ⅲ diet Ⅲ genetics Ⅲ genetic polymorphisms T he dyslipidemia associated with obesity, metabolic syndrome, insulin resistance, and type 2 diabetes consists of increased triglyceride, reduced high-density lipoprotein (HDL) cholesterol, and increased numbers of small, dense low-density lipoprotein (LDL) particles. 1,2 The strong interrelationships of these changes and their associations with increased risk for atherosclerotic cardiovascular disease have led to their collective designation as atherogenic dyslipidemia. 3 This dyslipidemia results from complex interactions among predisposing genetic traits and modifying factors including age, gender, and adiposity. Current recommendations for managing the cardiovascular disease risk associated with atherogenic dyslipidemia focus on lifestyle modifications that have been shown to be of benefit, particularly in reduction of excess adiposity and increase in physical activity. 4 The guidelines from the Adult Treatment Panel III of the National Cholesterol Education Program state that the principal lipid target for patients with metabolic syndrome should be LDL cholesterol, or in the case of individuals with triglyceride levels Ͼ200 mg/dL, non-HDL cholesterol. 5 Diet remains the mainstay for LDL cholesterol management in this syndrome, but optimal dietary treatment requires consideration of factors that influence the spectrum of atherogenic lipoprotein changes, including those that lead to the increased concentrations of small, dense LDL particles found in this syndrome. As reviewed, ...

Small, dense low‐density lipoproteins (LDL) are predictors of cardio‐ and cerebro‐vascular events in subjects with the metabolic syndrome

“…It is known that the therapeutical modulation of low HDL-cholesterol and high triglycerides significantly reduce cardiovascular risk [3] and lipid-lowering agents are also effective in reducing levels of small, dense LDL [26][27][28]. Dietary management is also of importance in such category of high-risk subjects [29,30]. In conclusion, this is the first study that evaluated the predictive role of small, dense LDL beyond traditional cardiovascular risk factors in subjects with the metabolic syndrome and without overt CAD.…”

Small dense low-density lipoprotein particles: priority as a treatment target in Type 2 diabetes?

“…Based on these measurements, it was recognized that individual lipid profiles normally cluster into two patterns of LDL size distribution: The majority of profiles demonstrates a predominance of large or medium sized LDL particles (LDL pattern A), whereas a substantial minority exhibits the LDL pattern B with a higher proportion of smaller LDL particles [16].…”

Insulin Resistance, Dyslipidemia, and Cardiovascular Disease

“…A low-fat, high-carbohydrate diet may have adverse effect in increasing phenotype B expression (2) but, unexpectedly, particularly reduces LDL cholesterol in individuals with phenotype B (3). Those with phenotype A show reduction in LDL1 with increase in LDL3, while with phenotype B there are decreases in LDL1 and LDL2 but increase in LDL4.…”