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Background: Stroke is a major cause of mortality and disability in modem societies. Statins are effective medications in decreasing cardiovascular events through lipid lowering and pleiotropic effects. Objective: To summarize current evidence regarding the role of statins in the prevention and management of stroke. Methods: A narrative review of current evidence regarding the effect of statins in stroke management. Electronic searches of MEDLINE, EMBASE and Cochrane Databases were performed. Results: In primary prevention of stroke in patients with risk factors but no established cardiovascular disease, potent statins such as atorvastatin and rosuvastatin have shown some benefits, but the clinical relevance of this effect is questionable. In populations at higher risk of stroke, such as patients with established coronary heart disease, the majority of relevant studies have shown a beneficial effect of statins in preventing stroke. Similarly, in patients with a previous cerebrovascular event, there is a clear benefit of statins for the prevention of recurrent events. The use of statins is not associated with an increased risk of intracranial bleeding in primary prevention studies. There may be an increased incidence of non-fatal hemorrhagic stroke with high dose statins in patients with a previous cerebrovascular event. Patients who experience a stroke while on statins should not discontinue statins. In addition, statins are associated with better survival and improved functional outcome when administered during the acute phase of stroke in statin-naive patients. In contrast, statins do not confer any benefit in patients with acute ischemic stroke who receive thrombolysis. Conclusion: Treatment with statins prevents ischemic stroke, especially in patients with high cardiovascular risk and established atherosclerotic disease. It seems that both lipid lowering and pleiotropic effects contribute to these effects.

Objective: Controversial findings exist regarding potential influence of statin therapy on diabetic incidence. Aim of this study was to investigate the role of long duration statin treatment on diabetes mellitus (DM) incidence of Heterozygous Familial Hypercholesterolemia (hFH) and Familial Combined Hyperlipidemia (FCH) patients. Methods: Study population consisted of 212 hFH and 147 FCH patients that visited Lipid Outpatient Department (mean follow up of 11 and 10 years respectively). Several clinical data such as history of DM, cardiovascular disease, thyroid function, metabolic syndrome, glucose levels, lipid profile and lifestyle data were obtained. In order to compare the effects of different doses of different types of statins, a “statin treatment intensity product” was used. Results: 14% of FCH and only 1% of hFH patients developed DM during follow up. Although univariate analysis showed a statistical trend (p = 0.06) in the association between new onset DM and statin treatment intensity (STI) in the FCH subgroup of patients with normal baseline glucose levels, this was no longer significant after adjusting for several confounders. Furthermore, the type of statins used did not seem to play a role in the development of DM either in hFH or FCH patients. Conclusion: Long duration of high STI does not seem to be associated with diabetic risk in hFH patients. High STI used in the FCH population is not associated with increased risk of new onset DM compared to low STI. Further studies are required in order to clarify the potential diabetogenic effects of statins in these high risk populations. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Background: Familial combined hyperlipidemia (FCH) is an inherited lipid disorder associated with premature cardiovascular disease. It has not been established whether the cardiometabolic risk factors, which frequently accompany FCH, such as diabetes, metabolic syndrome (MetS) and hypertension, modulate cardiovascular risk in FCH patients. Methods and Results: In this single-center, retrospective study, 695 FCH patients with adequate follow-up were enrolled (mean age, 48.9 years; 455 male). Risk factors including lipid levels were evaluated before the initiation of treatment. Acute myocardial infarction (AMI) and cardiovascular death were recorded during a mean follow-up of 9 years. The combined endpoint (AMI and/or cardiovascular death) occurred in 41 patients (5.9% of the total). Those FCH patients who reached the combined endpoint had lower high-density lipoprotein cholesterol (HDL-C) than those who did not, but levels of other lipid variables were similar. Presence of hypertension, diabetes or MetS was a predictor of the combined endpoint on univariate Kaplan-Meier analysis (all P

Background and Purpose Microwave radiometry allows noninvasive in vivo measuring of internal temperature of tissues reflecting inflammation. In the present study, we evaluated the predictive accuracy of this method for the diagnosis of coronary artery disease (CAD). Methods Consecutive patients (n=287) scheduled for coronary angiography were included in the study. In carotid arteries of both groups, the following measurements were performed: (1) intima-media thickness (IMTmax) and (2) temperature measurements by microwave radiometry (T-max). C-statistic and net reclassification improvement were used to compare the prediction ability of the markers IMTmax and T-max for the presence of CAD and multivessel CAD. Results Of 287 patients, 239 had stenoses 50% (CAD group), and 48 did not have significant stenoses (NO-CAD group). T-max was an independent predictor for the presence of CAD and multivessel CAD, showing similar predictive accuracy to intima-media thickness, as assessed by c-statistic and net reclassification improvement. Conclusions Local inflammatory activation, as detected by microwave radiometry, has similar predictive accuracy to intima-media thickness for the presence and extent of CAD.

Background: To evaluate the impact of familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) on arterial properties and the effects of statins. Methods: We meta-analyzed 51 studies providing data for 4,057 FH patients and 732 FCH patients with random-effects models, meta-regression analysis and publication bias analysis. The main outcomes of interest were (1) brachial artery flow-mediated dilation (FMD), (2) intima-media thickness (IMT), and (3) change of IMT and FMD after treatment with statins. Results: Compared to normolipidemic controls, FH patients had lower FMD [pooled mean difference (MD): 5.31%, 95% CI 7.09 to 3.53%, P < 0.001] and higher carotid IMT (pooled MD: 0.12 mm, 95% CI 0.09-0.15 mm, P < 0.001) and femoral IMT (pooled MD: 0.35 mm, 95% CI 0.18-0.51 mm, P < 0.001). FCH patients had lower FMD and increased IMT (pooled MD: -3.60%, 95% CI -6.69 to -0.50%, P = 0.023; and 0.06 mm, 95% CI 0.04-0.08 mm, P < 0.001, respectively). Total and LDL-cholesterol was a significant determinant of FMD and carotid IMT in FCH patients and of FMD and femoral IMT in FH patients. In FH patients, statins improved FMD (pooled MD of change: 5.39%, 95% CI 2.86-7.92%, P < 0.001) and decreased carotid IMT (pooled MD of change: -0.025 mm, 95% CI -0.042 to -0.009 mm, P = 0.003). Changes of both FMD and IMT with statins correlated with the duration x treatment intensity product in FH patients (both P < 0.01). Additionally, statins improved FMD in FCH patients (pooled MD of change: 2.06%, 95% CI 0.43-3.69%, P = 0.013). No significant publication bias was detected. Conclusion: Arterial properties are impaired in subjects with FH or FCH. Statins improve arterial function and structure in FH patients in a treatment intensity-related manner. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

We evaluated the efficacy and the safety of combining high doses of statins and ezetimibe in heterozygous familial hypercholesterolemia (hFH) patients. Seventy patients with hFH, received 10 mg of ezetimibe, in addition to their current statin therapy and were followed up for twelve months. The co-administration of statins and ezetimibe improved total cholesterol (p < 0.05), LDL-c(p < 0.05), triglycerides (p < 0.05) and apolipoprotein-B (p < 0.05) in comparison to statin monotherapy. There were no changes in high density lipoprotein cholesterol (HDL-c), apolipoprotein-A, lipoprotein (a), fibrinogen and C-reactive protein (CPR). In conclusion the combination of 10 mg of ezetimibe with high dose statin therapy is effective in hFH, offering a further reduction of LDL-c throughout the 12 months of follow up. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Background; Familial combined hyperlipidaemia (FCH) is all inlicrited dyslipidaernia that is related to a high risk of coronary artery disease (CAD). We evaluated the prevalence of CAD in a large FCH population and the association of risk factors with CAD accordino to gender. Methods: In this single-center, observational study, lipid and lipoprotein variables were measure in untreated patients with FCH (565 males and 302 females). CAD was defined as a documented history of myocardial infarction or coronary revascularization, or all abnormal coronary angiogram (stenosis of >50% in in epicardial coronary artery), or angina plus abnormal imaging stress test. Results: Males had higher triglyceride level (P < 0.001) but lower total cholesterol (P < 0.001) and HDL-cholesterol level (P< 0.001) compared to women. The prevalence of CAD was 22.2% in men and 4.6% in women (P

Aims Recent studies suggest an association between acute inflammation and deterioration of arterial function. The effect of acute inflammation on endotheliat function and the rote of treatment with statins have not been investigated in subjects with dystipidaemia. Methods and results In this randomized, placebo-controlled, double-blind study, we generated a transient systemic inflammation by Salmonella typhi vaccination in 50 volunteers with mild hypercholesterotaemia after 4 days of treatment with atorvastatin 40 mg or placebo once daily. Endothelium-dependent flow-mediated dilation (FMD) of the brachial. artery and circulating levels of endothelial, and inflammatory markers were measured before and 8 h after the vaccine. Vaccination produced a decline on FMD at 8 h (absolute decrease of 2.55%, P = 0.001), indicating an unfavourable effect on endotheliat function. In contrast, in atorvastatin-treated subjects, FMD was preserved after vaccination (decrease of 0.15%, P = 0.005 vs. placebo). The vaccination-induced decline in plasma level of nitric oxide metabolites (by 6.0 mu mol/L, P = 0.007) and antioxidant capacity (by 20.6 mu mol/L, P = 0.001) in the placebo group were completely abolished by atorvastatin (P = 0.038 and P = 0.005, respectively, vs. placebo). In contrast, atorvastatin had no significant effect on cytokine levels. Conclusion Acute inflammation is aetiologically associated with the deterioration of vasomotor and systemic endotheliat function in hypercholesterolaemic patients. Atorvastatin effectively abrogates these deleterious effects.

Background: Heterozygous familial hypercholesterolemia (hFH) and familial combined hyperlipidemia (FCH) have been associated with increased risk for coronary artery disease (CAD), but the impact of traditional risk factors to the incidence of CAD in these patients remains unknown. The present study evaluates the contribution of such risk factors to the development of CAD in these two dyslipidemic populations. Methods: This cross-sectional study enrolled a total 1306 subjects; 600 individuals with hFH (mean age 41 13 years, 261 males and 339 females), and 706 individuals with FCH (mean age 49 11 years, 463 males and 243 females). Blood samples were collected after 12 hours fasting period, and serum lipids were determined. Multivariate logistic regression models were used to estimate the odds ratios of CAD based on the type of hyperlipidemia, after adjustment for demographic characteristics and risk factors. Results: Subjects with FCH were older (P