LDL-cholesterol control in the primary prevention of cardiovascular diseases: An expert opinion for clinicians and health professionals.

AIMS: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. DATA SYNTHESIS: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. CONCLUSIONS: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk.

Adipose tissue dysfunction and metabolic disorders: Is it possible to predict who will develop type 2 diabetes mellitus? Role of markErs in the progreSsion of dIabeteS in obese paTIeNts (The RESISTIN trial).

The aim of this study was to valuate if there are some differences in metabolic parameters among obese which will develop diabetes and those that will not develop diabetes. We enrolled 959 obese, normal glucose tolerant, of either sex, outpatients and evaluated them for 8 years. We evaluated: body mass index (BMI), waist circumference (WC), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index, blood pressure, lipid profile, lipoprotein(a), adiponectin (ADN), resistin, leptin, high sensitivity reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), retinol binding protein-4 (RBP-4), adipsin, vaspin, visfatin, omentin-1, chemerin. After 8 years of observation, 429 patients maintained euglycemia, while 133 patients developed dysglycemia, and 90 developed diabetes. In dysglycemic patients, ADN was lower, and resistin was higher compared to baseline, while in diabetic patients ADN was lower, and resistin was higher both compared to baseline, and compared to euglycemic and dysglycemic patients. High sensitivity C-reactive protein, TNF-α were higher in both dysglycemic and diabetic patients compared to baseline, but the values recorded in diabetics were higher both compared to euglycemic and dysglycemic. Visfatin was higher and omentin-1 was lower compared to baseline, and compared to euglycemic patients in diabetics. Odds ratio showed that lower levels of adiponectin and higher levels of resistin, but not of other cytokines, increased the risk of developing type 2 diabetes mellitus. Data seem to suggest that lower levels of adiponectin, and higher levels of resistin can be predictive of a future diabetes in obese people, even years before the disease onset.

Glyco-metabolic control, inflammation markers, and cardiovascular outcomes in type 1 and type 2 diabetic patients on insulin pump or multiple daily injection (italico study).

BACKGROUND: To evaluate if the positive effects recorded on glycaemic control with continuous subcutaneous insulin infusion (CSII) were maintained on the long-term compared with multiple daily injection (MDI). The secondary objective was to evaluate if there is a reduction of type and number of cardiovascular events (CV). METHODS: This retrospective, observational study evaluated glycaemic control and the number of CV in 104 patients with type 1 or 2 diabetes previously treated with MDI and initiating CSII therapy with tubed insulin pumps compared with 109 patients previously treated with MDI continuing MDI. RESULTS: After 8 years, the glycaemic control including glycated haemoglobin (HbA1c ), fasting plasma glucose (FPG), and prandial plasma glucose (PPG) improved with both CSII and MDI compared with baseline; however, HbA1c , FPG, and PPG recorded with CSII were lower than data recorded with MDI. During the 8 years, there were fewer CV events with CSII, compared with MDI, and in particular, there were fewer cases of atrial fibrillation, premature ventricular contractions, acute coronary infarction, angina pectoris, heart failure, and peripheral vascular ischemia. We did not record any reduction of ischemic stroke events. CONCLUSION: Our preliminary data suggest that CSII treatment seems to reduce the rates of CV compared with MDI therapy. Moreover, CSII also improved glycaemic control, without increasing the number of hypoglycaemia. However, given the observational design of this trial, our data should be validated in a randomized clinical trial; if they will be confirmed, CSII could be chosen for fully informed and motivated patients at higher risk of developing CV.

Effects of Sitagliptin on Lipid Profile in Patients With Type 2 Diabetes Mellitus After 7 Years of Therapy.

The aim of this study was to investigate whether the effects of sitagliptin on lipid profile were maintained even after 7 years of treatment. We treated 591 patients who had not been well controlled by current therapy with the addition of sitagliptin 100 mg/d. Data were compared with those of 612 patients treated with sulfonylureas plus metformin, pioglitazone plus metformin, and pioglitazone plus sulfonylureas. We observed that, compared with patients treated with sulfonylureas plus metformin, patients receiving sitagliptin in addition to metformin experienced a greater decrease of total cholesterol and low-density lipoprotein cholesterol (LDL-C) compared with baseline and with sulfonylureas plus metformin. Compared with patients treated with metformin plus pioglitazone, sitagliptin resulted in a greater reduction of total cholesterol and LDL-C relative to baseline and to metformin plus pioglitazone. We also observed a higher increase of high-density lipoprotein cholesterol (HDL-C) after sitagliptin had been added to pioglitazone, both compared with baseline and to the competitor. Compared with patients treated with pioglitazone plus sulfonylureas, the combination of sitagliptin and sulfonylureas was more effective in reducing LDL-C and in increasing HDL-C. High-sensitivity C-reactive protein was decreased by all pharmacological combinations. We can conclude that the addition of sitagliptin led to a better and more durable improvement of lipid profile compared with sulfonylureas or thiazolidinediones.

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effectiveness of a Food Supplement Containing Creatine and D-Ribose Combined with a Physical Exercise Program in Increasing Stress Tolerance in Patients with Ischemic Heart Disease.

The aim of this study is to establish whether a supplement of creatine and ribose combined with a physical exercise program can improve the total work capacity during exercise in a population of patients with known ischemic heart disease. A double-blind, six-month study was designed in which 53 patients were enrolled and randomized to take either a nutraceutical composition containing creatine, D-ribose, vitamin B1, and vitamin B6 (active treatment) or the placebo. Both the nutraceutical supplement and the placebo were supplied by Giellepi S.p.A. Health Science in Lissone, Italy. After six months of study, the cardiac double product at the peak of the load, the delta double product, and the chronotropic index were higher in the active treatment group than in the placebo group. We can conclude that a supplementation with creatine, D-ribose, vitamin B1, and vitamin B6, in addition to standard therapy and a physical exercise program, seems to be helpful in improving exercise tolerance compared to the placebo in a population with cardiovascular disease. However, this needs to be further studied, given that there is no clear evidence that the double product can be used as a surrogate measure of exercise tolerance.

Effects on oral fat load of a nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols: A randomized, placebo controlled trial.

BACKGROUND: In literature, there are several studies about the effects of nutraceutical combinations at fasting, but data in post-prandial phase are lacking. PURPOSE: We planned a study to evaluate the efficacy and safety of a nutraceutical agent containing fermented red rice, phytosterols and olive polyphenols compared to placebo in a sample of Caucasian patients with low cardiovascular risk, both at fasting and after an oral fat load. STUDY DESIGN: Eighty patients were randomized to receive, as addition to diet and physical activity, a nutraceutical combination containing fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols or placebo (control group), once a day. METHODS: We evaluated at baseline, and after 3 months: body mass index, fasting plasma glucose, lipid profile, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble endothelial-leukocyte adhesion molecule-1. We evaluated these parameters both at fasting, and after an oral fat load. RESULTS: Nutraceutical combination gave a reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). We recorded a reduction of soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and sE-selectin in the group treated with nutraceutical combination, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). Parameters recorded during oral fat load improved compared to the oral fat load performed at baseline with the nutraceutical combination. CONCLUSIONS: The nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols seems to be effective in improving lipid profile and markers of endothelial damage in dyslipidemic patients in primary prevention at low risk for developing cardiovascular disease. The true novelty of this study, however, is the improvement of endothelial damage after an oral fat load compared to placebo.