ABSTRACT
BACKGROUND: Over the last decades, the reduction of the mortality and morbidity of stroke has been a high- priority objective worldwide. Statins, or 3-hydroxy-3- methylglutaryl coenzyme A (HMG- CoA) reductase inhibitors, have emerged as the predominant preventive strat egy to tackle the worldwide stroke burden. Currently, statins are considered the most important advance in stroke prevention since the introduction of aspirin and antihypertensive treatments. METHODS: In this paper we review the current evidence regarding the role of statins in the stroke prevention and future directions in this field. RESULTS: A meta-analysis of random ised trials of statins has shown that each 1 mmol/L (39 mg/dL) decrease in low-density lipoprotein cholesterol, equates to a reduction in relative risk for stroke of 21.1%. Statins are now recommended for the primary prevention of ischemic stroke in patients estimated to have a high 10-year risk for cardiovascular events. Nevertheless, until recently there was little evidence that statin therapy reduced the risk of stroke recurrence. The SPARCL, published in 2006, was the first trial to show the benefits of statin therapy in preventing recurrent stroke. Now we know that statins reduce the risk of stroke recurrence by 12-16% and statins are recommended among patients with ischemic stroke or TIA presumed to be of atherosclerotic origin or with other comorbid atherosclerotic cardiovascular disease. CONCLUSION: Traditionally, there has been no clear data demonstrating that adding other lipid-modifying drugs to statins results in a further decrease in stroke or other cardiovascular event, but now things have changed and future directions include combinations with ezetimibe and new treatments such as PCSK9 inhibitors. Only time will tell the real roll of these new promising non-statin lipidmodifying therapies on stroke prevention.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Stroke/prevention & control , HumansABSTRACT
BACKGROUND: A recent genome-wide association study (GWAS) has identified a putative association, not statistically confirmed, of cervical dystonia within several regions in a British population. Hence, the authors proposed dysfunction of the ion channel NALCN (for sodium leak channel, nonselective) as a plausible cause of cervical dystonia. The objective of our study was to investigate the association of five single nucleotide polymorphisms (SNPs) previously reported with high signals as putative genetic risk factors for cervical dystonia in a British GWAS, including two located in the NALCN gene region. METHODS: We performed a case-control association study in a Spanish population. The SNPs selected for genotyping were two SNPS in the NALCN gene (rs61973742 and rs1338041), one SNP in the OR4X2 gene (rs67863238), one SNP in the COL4A1 region (rs619152), and one intergenic SNP (rs1249277). Genomic DNA was collected from 252 patients with cervical dystonia, with a mean age of 55.3 ± 14.1 years (mean age at onset, 43.5 ± 15.7 years), and 342 unrelated control subjects with a mean age of 56.3 ± 14.3 years. Genotyping of SNPs was performed using TaqMan assays and SimpleProbe assays. RESULTS: The SNP rs619152 had to be excluded because of assay failure. No significant differences were found in allele distribution between cases and controls for all analyzed SNPs. Therefore, we found no association with cervical dystonia for the analyzed SNPs in our Spanish population. CONCLUSIONS: We did not find any evidence supporting the association of NALCN with cervical dystonia, indicating that this gene is not implicated in the pathogenesis of this disorder in our cervical dystonia population.
Subject(s)
Dystonia/genetics , Gene Frequency/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide/genetics , Adult , Age of Onset , Aged , Case-Control Studies , Female , Genome-Wide Association Study/methods , Genotype , Humans , Middle Aged , Risk , White PeopleSubject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Stroke/prevention & control , Blood Pressure/physiology , Humans , Hypertension/complications , Hypertension/physiopathology , Multicenter Studies as Topic , Stroke/physiopathologyABSTRACT
Historically, the etiological link between hypercholesterolemia and stroke has been less clear than for coronary heart disease. The lack of association between cholesterol levels and stroke in most epidemiological and observational studies has brought about this controversy. Many recent, long-term clinical studies have confirmed that statin therapy results in a reduced risk of strokes, even in so-called "normocholesterolemic" patients. The magnitude of the effect is great. A large-scale analysis of more than 90,000 individuals showed that every 10% reduction in the concentration of LDL-cholesterol reduces the risk of stroke by 15.6%. The positive effect of statins on stroke depends mainly on LDL cholesterol reduction, but other non-lipid mechanisms, so-called "pleiotropic" effects, have been shown to play a role. This review seeks to summarize the role of statins in stroke prevention. Despite the fact that our understanding of the benefits of statins in stroke prevention is still evolving, we find marked room for improvement in stroke risk factor management. Internists must face this challenge and integrate this new knowledge into their daily clinical practice.
