Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heterozygous familial hypercholesterolemia (FH) is an autosomal dominant disorder known to be associated with elevated cholesterol levels and increased risk of premature coronary heart disease. Since increased cholesterol levels lead to atherosclerosis, FH has also been proposed as a risk factor for peripheral vascular and ischemic cerebrovascular disease. Currently, the association between clinical FH and risk of stroke is unclear: Two studies conducted in the 1980s indicated an increased risk of stroke in FH subjects; however, two others found no higher risk, and all had methodological limitations. A recent prospective study of familial hypercholesterolemia by the United Kingdom-based Simon Broome Register Group did not find an excess risk of stroke mortality for subjects with clinical FH. By contrast, the prevalence of peripheral arterial disease is increased from five- to 10-fold in FH subjects compared with non-FH controls. In addition, the intima-media thickness of the carotid and/or femoral artery is increased in FH subjects. Better understanding of the association between FH and the incidence of ischemic stroke events could have a public health impact by improving the diagnosis, prognosis, and treatment of individuals with FH and their relatives and by elucidating the relation between cholesterol levels and ischemic cerebrovascular disease.
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PMID:Familial hypercholesterolemia, peripheral arterial disease, and stroke: a HuGE minireview. 1532 39

Heterozygous familial hypercholesterolemia (HeFH) is a common (early estimates suggested a prevalence of 1 in 500 individuals, but recent studies have indicated that it may be higher) genetic disorder characterized by markedly elevated plasma concentrations of low-density lipoprotein cholesterol (LDL-C). HeFH is associated with an elevated risk of premature coronary heart disease, stroke, and peripheral vascular disease. Despite the availability of reliable diagnostic criteria (high LDL-C levels, family history or premature CHD and hypercholesterolemia, cerebral/peripheral vascular disease, and the presence of tendon xanthomata or presence of arcus cornealis before age of 45), HeFH is underdiagnosed and undertreated worldwide. Moreover, while there are effective treatments available to decrease LDL-C and prevent early-onset heart disease in individuals with HeFH, because of the high baseline levels of LDL-C, the achievement of target LDL-C levels remains a challenge. In recent years, a number of novel therapies to lower LDL-C levels in HeFH have been developed, including the monoclonal antibodies against serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9), alirocumab and evolocumab, which have the potential to reduce LDL-C by an additional 50%-60% when prescribed in combination with standard lipid-lowering drugs. This review summarizes the challenges in clinical management of subjects with HeFH, with a focus on emerging treatments, and highlights the status of HeFH diagnosis and treatment in Italy.
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PMID:Old challenges and new opportunities in the clinical management of heterozygous familial hypercholesterolemia (HeFH): The promises of PCSK9 inhibitors. 2799 83

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder predisposing affected individuals to lifelong low-density lipoprotein cholesterol (LDL-C) elevation and coronary heart disease. However, whether HeFH increases the risk of peripheral arterial disease (PAD) and ischemic stroke is undetermined. We examined associations between HeFH and these outcomes in a comprehensive systematic review and meta-analysis. We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed (for ahead-of-print publications) for relevant English-language studies. Maximally adjusted risk estimates were pooled under random- and fixed-effects meta-analysis to derive odds ratios (ORs) and 95% confidence intervals (CIs). We included 6 studies representing 183 388 participants. Heterozygnous familial hypercholesterolemia was associated with a higher risk of PAD (OR: 3.59 [95% CI: 1.30-9.89]). This trend was nonsignificantly preserved (OR: 2.96 [95% CI: 0.68-12.88]) in sensitivity analyses of genetically defined HeFH. Genetic HeFH was not associated with increased ischemic stroke risk (OR: 0.76 [95% CI: 0.37-1.58]) although possessing an LDL-C >4.9 mmol/L (190 mg/dL) was (OR: 1.42 [95% CI: 1.06-1.89]). We found clinical and genetic diagnoses of HeFH to be associated with increased PAD risk. Genetically confirmed HeFH may not confer an increased risk of ischemic stroke. Modest associations may exist between LDL-C and ischemic stroke risk in HeFH.
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PMID:Risk of Ischemic Stroke and Peripheral Arterial Disease in Heterozygous Familial Hypercholesterolemia: A Meta-Analysis. 3081 53