Statins in Stroke

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

Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis

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

Subclinical Left Ventricular Systolic Dysfunction in HIV Patients: Prevalence and Associations with Carotid Atherosclerosis and Increased Adiposity

Background: Human immunodeficiency virus (HIV) is mainly detected in young, otherwise healthy, individuals. Cardiomyopathy and peripheral artery disease affecting these patients appears to be multifactorial. Prompt and potentially more effective implementation of therapeutic measures could be enabled by pre-symptomatic diagnosis of myocardial dysfunction and peripheral artery damage. However, limited data is available to date on this specific topic. Μethods: We investigated the association between global longitudinal strain (GLS), an established index of subclinical left ventricular systolic dysfunction (LVSD) assessed by two-dimensional speckle-tracking echocardiography, and: (a) patient history; (b) demographic and clinical baseline characteristics; (c) carotid intima-media thickness (IMT) and the presence of carotid atherosclerotic plaque(s), measured by ultrasonography; (d) temperature difference (ΔT) along each carotid artery, measured by microwave radiometry; and (e) basic blood panel measurements, including high-sensitivity troponin-T (hsTnT) and NT-proBNP in people living with HIV (PLWH) and no history of cardiovascular disease. Results: We prospectively enrolled 103 consecutive PLWH (95% male, age 47 ± 11 years, anti-retroviral therapy 100%) and 52 age- and sex-matched controls. PLWH had a significantly higher relative wall thickness (0.38 ± 0.08 vs. 0.36 ± 0.04, p = 0.048), and higher rate of LVSD (34% vs. 15.4%, p = 0.015), and carotid artery atherosclerosis (28% vs. 6%, p = 0.001) compared with controls. Among PLWH, LVSD was independently associated with the presence of carotid atherosclerosis (adj. OR:3.09; 95%CI:1.10–8.67, p = 0.032) and BMI (1.15; 1.03–1.29, p = 0.017), while a trend for association between LVSD and left ventricular hypertrophy was also noted (3.12; 0.73–13.33, p = 0.124). No differences were seen in microwave radiometry parameters, NT-proBNP, hs-TnT and c-reactive protein between PLWH with and without LVSD. Conclusions: Subclinical LVSD and carotid atherosclerosis were significantly more frequent in PLWH compared to a group of healthy individuals, implying a possible link between HIV infection and these two pathological processes. Carotid atherosclerosis and increased adiposity were independently associated with impaired GLS in HIV-infected individuals

Morphological and Functional Assessment of Carotid Plaques Have Similar Predictive Accuracy for Coronary Artery Disease

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

Protective effect of atorvastatin on acute systemic inflammation-induced endothelial dysfunction in hypercholesterolaernic subjects

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