Matilda Florentin

“European Panel on Low Density Lipoprotein (LDL) Subclasses”: A Statement on the Pathophysiology, Atherogenicity and Clinical Significance of LDL Subclasses

Aim of the present Consensus Statement is to provide a comprehensive and up to-date document on the pathophysiology, atherogenicity and clinical significance of low density liproproteins (LDL) subclasses. We sub-divided our statement in 2 sections. section I discusses the pathophysiology, atherogenicity and measurement issues, while section II is focused on the effects of drug and lifestyle modifications. Suggestions for future research in the field are highlighted at the end of section II. Each section includes Conclusions.

Sibutramine‐associated adverse effects: a practical guide for its safe use

Obesity is a multifactorial chronic disorder which comprises a serious health problem nowadays. The effective management of obesity is difficult in contemporary societies where abundance of hypercaloric food and sedentary lifestyle is the rule. Apart from lifestyle interventions, which include diet, exercise and behavioural treatment, weight‐loss medications can also be used for the management of obesity. Sibutramine, a selective monoamine reuptake inhibitor, is a drug with established efficacy in sustained weight reduction and an overall favourable safety profile. However, its action on the sympathetic nervous system has linked sibutramine to blood pressure and heart rate elevations. These potentially adverse effects as well as other sibutramine‐associated side effects and their possible underlying mechanisms are reviewed in the present article. Compelling evidence from the majority of data in the literature shows that sibutramine can be effectively used in conjunction with caloric restriction and exercise in obese patients. Hypertension, if adequately treated and frequently monitored, is not an absolute contraindication for the prescription of sibutramine.

Compliance with lipid-lowering therapy and its impact on cardiovascular morbidity and mortality

Background: Hypercholesterolemia is a major risk factor for cardiovascular disease. Objective: Treatment with hypolipidemic agents reduces the risk of vascular events both in primary and secondary prevention. Although compliance with lipid-lowering therapy is an important determinant of cardiovascular clinical outcomes, relatively little attention is being paid to this issue by physicians. Methods: We searched the literature using Pubmed up to 5 August 2008. Results: Compliance with lipid-lowering therapy is poor in clinical practice, especially in primary prevention. As many as 6 out of 10 patients may stop taking statins during the first 6 months following initiation of treatment. Poor compliance has been associated with worse clinical outcome and increased cardiovascular morbidity and mortality. Importantly, statin withdrawal may be even worse compared with not taking statins at all. Several strategies may increase treatment adherence. Conclusions: Poor compliance with lipid-lowering treatment is an important health issue that has been associated with unfavorable cardiovascular outcome. Increasing adherence rates should become a major concern for physicians.

Vitamin D and Cardiovascular Disease: A Novel Agent for Reducing Cardiovascular Risk?

Vitamin D deficiency is a well-established risk factor for bone disease. Emerging data suggest a pleiotropic role of this agent in a variety of functions in humans. Epidemiological studies indicate an inverse association between vitamin D deficiency and the prevalence of cardiovascular disease (CVD), as well as individual cardiometabolic risk factors, such as hypertension, diabetes, dyslipidemia and the metabolic syndrome. Moreover, vitamin D deficiency has been implicated in the atherosclerotic process. This review considers current data regarding the role of vitamin D deficiency in the development of CVD and addresses the effect of supplementation on cardiovascular outcomes.

Effects of rosuvastatin combined with olmesartan, irbesartan, or telmisartan on indices of glucose metabolism in Greek adults with impaired fasting glucose, hypertension, and mixed hyperlipidemia: a 24-week, randomized, open-label, prospective study.

BACKGROUND Statin therapy has been reported to be associated with new-onset diabetes. Angiotensin II-receptor blockers (ARBs) are effective antihypertensive drugs that have been reported to activate peroxisome proliferator-activated receptor gamma (PPARgamma) to differing extents, with favorable effects on glucose metabolism and the incidence of new-onset diabetes. Among the ARBs, telmisartan is a partial activator of PPARgamma, irbesartan is a weak partial activator, and olmesartan has no effect on PPARgamma activation. OBJECTIVE The goal of this study was to evaluate the effects on glucose homeostasis of combining rosuvastatin with ARBs of varying PPARgamma-activating potency in Greek adults with impaired fasting glucose, mixed dyslipidemia, and stage 1 hypertension. METHODS This was a 24-week, randomized, open-label study. Inclusion criteria were impaired fasting plasma glucose (FPG) (100-125 mg/dL [5.6-6.9 mmol/L]), mixed dyslipidemia (LDL-C >160 mg/dL [4.14 mmol/L] and triglycerides >150 mg/dL [1.69 mmol/L]), and stage 1 hypertension (systolic blood pressure 140-159 mm Hg and/or diastolic blood pressure 90-99 mm Hg). After 12 weeks of dietary intervention, patients were randomly allocated to receive rosuvastatin 10 mg/d plus telmisartan 80 mg/d (RT group), irbesartan 300 mg/d (RI group), or olmesartan 20 mg/d (RO group) for 24 weeks. The primary end point was change in the following indices of glucose metabolism after 6 months of treatment: FPG, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of beta-cell function (HOMA-B), and glycosylated hemoglobin (HbA(1c)). Secondary end points included changes in anthropometric variables, blood pressure, serum lipids, and high-sensitivity C-reactive protein (hs-CRP). Tolerability was monitored throughout the study. RESULTS After the 12-week dietary intervention, 151 white patients (78 female, 73 male) met the inclusion criteria and were randomized to receive RT (n = 52), RI (n = 48), or RO (n = 51). The mean (SD) age of the 3 groups was 60 (10), 60 (10), and 58 (12) years, respectively; their mean weight was 79 (11), 81 (12), and 78 (11) kg. At 6 months, the RT group had a 29% decrease in HOMA-IR (from a median [range] of 2.6 [0.6-6.6] to 1.8 [0.5-5.1]), the RI group had a 16% increase (from 2.5 [0.5-6.2] to 2.9 [0.5-8.1]), and the RO group had a 14% increase (from 2.4 [0.5-7.9] to 2.7 [0.5-5.2]) (all, P < 0.05 vs baseline). The improvement in the RT group was statistically significant compared with the RI group (P < 0.01) and the RO group (P < 0.05). The changes from baseline in FPG and HbA(1c) were not significant in any group. Fasting serum insulin decreased by 21% in the RT group (from 10.4 [2.4-28.1] to 8.2 [2.4-18.8] microU/mL), whereas it increased by 12% in the RI group (from 9.1 [2.0-26.5] to 10.2 [2.0-25.2] microU/mL) and by 8% in the RO group (from 10.1 [2.0-29.6] to 10.9 [2.0-19.1] microU/mL) (all, P < 0.05 vs baseline). Again, there was a significant difference between the RT group and the RI group (P < 0.01) and RO group (P < 0.05). Levels of hs-CRP decreased by 44% in the RT group (from 2.2 [0.3-7.9] to 1.2 [0.4-7.0] mg/L), by 12% in the RI group (from 2.2 [0.3-12.3] to 1.9 [0.2-11.4] mg/L), and by 22% in the RO group (from 2.1 [0.7-4.0] to 1.7 [0.7-6.2] mg/L). The difference was statistically significant for the RT group compared with baseline and with the RI and RO groups (all comparisons, P < 0.05). Blood pressure was significantly reduced from baseline in all 3 groups, with no significant differences between groups. No serious adverse events were reported during the study, nor were there any clinically significant elevations in aminotransferases or creatine kinase. CONCLUSION In this small, randomized, open-label study, the RT combination had favorable effects on HOMA-IR, fasting serum insulin, and hs-CRP compared with the RI and RO combinations in Greek adults with impaired fasting glucose, mixed hyperlipidemia, and stage 1 hypertension.

Ezetimibe-associated adverse effects: what the clinician needs to know

Objective:  Ezetimibe is a relatively new lipid lowering agent, which is indicated for the treatment of primary hypercholesterolaemia, either as monotherapy or in combination with other hypolipidaemic drugs. The objective of the present article was to review the side effects attributed to ezetimibe administration and discuss their possible underlying mechanisms. Moreover, we aimed to comment on the possible drug interactions of ezetimibe and present current guidelines regarding its safe use.

Colesevelam hydrochloride in clinical practice: a new approach in the treatment of hypercholesterolaemia.

ABSTRACT Objective: Hypercholesterolaemia is a major risk factor for atherosclerosis and coronary heart disease. Treatment with lipid lowering agents reduces the risk of vascular events. Colesevelam is a novel bile acid sequestrant (BAS) indicated for the treatment of hypercholesterolaemia, either as monotherapy or in combination with statins. Scope: This article reviews the efficacy, tolerability and safety of colesevelam in clinical practice. The literature search was based on a PubMed search up to January 2008. Findings: Colesevelam, used alone or in combination with other hypolipidaemic agents (statins, ezetimibe and fenofibrate), has an overall favourable effect on lipid profile. Specifically, colesevelam reduces total and low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B levels and increases high-density lipoprotein cholesterol and apolipoprotein AI. However, colesevelam may slightly raise triglyceride levels. Colesevelam can improve glycaemic control in diabetic patients. Moreover, it may have anti-inflammatory properties, as it can reduce high sensitivity C-reactive protein concentration. Colesevelam almost lacks the intense side effects of previously used BASs, thus resulting in better patient compliance. However, the dose regimen consisting of up to 7 tablets/day and high cost may limit its use. Conclusions: Colesevelam is a safe alternative for those intolerant to other lipid lowering medication. This BAS also provides an option for patients who do not reach their LDL-C goal despite treatment with a statin.

Vitamin D and Metabolic Syndrome: Is There a Link?

In addition to bone homeostasis, vitamin D is involved in the physiological functions of several tissues and its insufficiency may contribute to various disorders. Vitamin D status seems to be associated with each of the components of metabolic syndrome (MetS), as well as MetS overall. We review these associations as well as the effects of vitamin D supplementation on MetS.

Effect of Non-Statin Lipid Lowering and Anti-Obesity Drugs on LDL Subfractions in Patients with Mixed Dyslipidaemia

Small, dense low density lipoprotein (sdLDL) particles are considered an emerging cardiovascular risk factor. Obese patients with mixed dyslipidaemia frequently have elevated sdLDL cholesterol (sdLDL-C) levels. Therefore, agents that favourably modulate the LDL phenotype may be of clinical value in these patients. We review the efficacy of anti-obesity and lipid lowering drugs other than statins on LDL subfractions in patients with mixed dyslipidaemia primarily focusing on those who are overweight/obese. The literature search was based on PubMed listings up to 26 November 2009. In most studies ezetimibe decreases the large and medium LDL subclasses and, to a lesser extent, the sdLDL particles, while it does not substantially influence LDL size. Fibrates and niacin reduce sdLDL particles and shift LDL size towards large, buoyant LDL particles. More studies are needed to elucidate the effects of fish oils and resins on LDL phenotype. Orlistat and rimonabant have been associated with reductions in sdLDL-C levels along with an increase in LDL particle size. We did not find any literature describing the effect of sibutramine on sdLDL profile. Treatment with fibrates and niacin seems to be beneficial in patients with mixed dyslipidaemia. The addition of orlistat may further improve LDL phenotype in overweight/obese patients.

The role of renin-angiotensin system inhibition in the treatment of hypertension in metabolic syndrome: are all the angiotensin receptor blockers equal?

The metabolic syndrome (MetS) is a strong predictor of cardiovascular morbidity and mortality, as well as new Type 2 diabetes. MetS consists of visceral obesity, elevated blood pressure, impaired glucose metabolism, atherogenic dyslipidaemia (elevated triglycerides and low levels of high-density lipoprotein cholesterol), as well as other metabolic abnormalities. The underlying pathophysiology seems to be largely, but not uniquely, attributable to insulin resistance. Existing antihypertensive drugs were designed to lower blood pressure rather than to modify the metabolic abnormalities associated with hypertension. This review considers the role of renin–angiotensin system inhibition and especially the use of angiotensin receptor blockers (ARBs) in the treatment of hypertension in MetS. There are differences among ARBs. Among them is the uricosuric effect of losartan. Furthermore, telmisartan may function as a partial agonist of the peroxisome proliferator-activated receptor-γ (PPAR-γ).