Dysfunctional Endothelial Progenitor Cells in Metabolic Syndrome

The metabolic syndrome (MetS) is highly prevalent and confers an increased risk of diabetes and cardiovascular disease. A key early event in atherosclerosis is endothelial dysfunction. Numerous groups have reported endothelial dysfunction in MetS. However, the measurement of endothelial function is far from optimum. There has been much interest recently in a subtype of progenitor cells, termed endothelial progenitor cells (EPCs), that can circulate, proliferate, and dfferentiate into mature endothelial cells. EPCs can be characterized by the assessment of surface markers, CD34 and vascular endothelial growth factor receptor-2, VEGFR-2 (KDR). The CD34+KDR+ phenotype has been demonstrated to be an independent predictor of cardiovascular outcomes. MetS patients without diabetes or cardiovascular diseases have decreased EPC number and functionality as evidenced by decreased numbers of colony forming units, decreased adhesion and migration, and decreased tubule formation. Strategies that have been shown to upregulate and enhance EPC number and functionality include statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome-proliferator-activating-receptor gamma agonists. Mechanisms by which they affect EPC number and functionality need to be studied. Thus, EPC number and/or functionality could emerge as novel cellular biomarkers of endothelial dysfunction and cardiovascular disease risk in MetS

Role of C-Reactive Protein in Contributing to Increased Cardiovascular Risk in Metabolic Syndrome

Metabolic syndrome is associated with increased propensity for diabetes and cardiovascular disease. Low-grade inflammation is characteristic of metabolic syndrome. C-reactive protein, the best characterized biomarker of inflammation, is also an independent predictor of future cardiovascular events. This review outlines the role of high-sensitivity C-reactive protein in contributing to increased cardiovascular risk in metabolic syndrome by inducing endothelial cell dysfunction and activating monocytes

Management of Hypertriglyceridemia in the Diabetic Patient

The hypertriglyceridemia of diabetes can be classified into mild to moderate (triglycerides between 150–499 mg/dL) and severe hypertriglyceridemia (triglycerides ≥500 mg/dL). As in any other individuals with hypertriglyceridemia, secondary causes need to be excluded. The management of severe hypertriglyceridemia (chylomicronemia syndrome) includes aggressive reduction of triglycerides with intravenous insulin, fibrates, omega-3 fatty acids, and/or niacin therapy to avert the risk of pancreatitis. In patients with mild to moderate hypertriglyceridemia, the treatment of choice is statin therapy to achieve the low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) target goals. The evidence base would favor niacin therapy in combination with statin therapy to achieve the goals pertaining to LDL cholesterol and non-HDL cholesterol. The data about the combination of fibrate therapy with statin therapy are disappointing

Statin Therapy in Metabolic Syndrome and Hypertension Post-JUPITER: What is the Value of CRP?

Much evidence supports a pivotal role for inflammation in atherosclerosis. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a cardiovascular risk marker and may also promote atherogenesis. CRP levels are increased in metabolic syndrome and hypertension and confer increased risk of cardiovascular events in patients in these subgroups. Statins have been shown to lower low-density lipoproteins and CRP independently, and reduce cardiovascular events in subjects with and without metabolic syndrome and hypertension. In this review, we focus on the results from the primary prevention statin trial, Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), which showed reductions in LDL, CRP, and cardiovascular events. Post-JUPITER, the new guidelines will now need to consider recommending high-sensitivity CRP testing to intermediate-risk metabolic syndrome patients and those with hypertension and intermediate risk so that we can better identify candidates at greater risk and reduce cardiovascular burden in these subjects with statin therapy