Statins decrease the risk of stroke in individuals with heterozygous familial hypercholesterolemia: A systematic review and meta-analysis.
BACKGROUND
Familial hypercholesterolemia (FH) is undoubtedly associated with premature coronary heart disease, but it is debatable whether FH increases the risk for stroke.


OBJECTIVE
To meta-analyze available evidence regarding the incidence of stroke in individuals with heterozygous (He) FH.


METHODS
We conducted a systematic review and a meta-analysis of epidemiological studies, including English-language publications until June 2015; four observational studies, with 3374 participants with HeFH, were included in the analysis. Cerebrovascular disease comprised of ischemic stroke or transient ischemic attack. Since studies did not include any control subjects, the corresponding general population of the same reference area and period of time for each HeFH study served as control group. Analyses were performed according to the period of time during which the studies were conducted: prestatin and statin era (before and after 1987 when lovastatin was launched).


RESULTS
In the prestatin era, individuals with HeFH exhibited a higher risk for stroke compared with the general population [odds ratio (OR) = 7.658, 95% confidence interval (CI): 6.059-9.678, p < 0.01]. In contrast, FH subjects had a lower odds for stroke following the generalization of statin therapy (OR = 0.251, 95% CI: 0.176-0.358, p < 0.01).


CONCLUSIONS
Taking into account the small number of studies and methodological issues, HeFH was associated with a higher risk of cerebrovascular disease compared with the general population in the prestatin era, which was significantly reduced after the introduction of statin therapy.
Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece. Electronic address: fotisbarkas@windowslive.com.
Fotios
F
Barkas
Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
Moses
M
Elisaf
Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece. Electronic address: hmilioni@uoi.gr.
Haralampos
H
Milionis
D000293:Adolescent; D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics; D003327:Coronary Disease / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000235:genetics; D015994:Incidence; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics; D055815:Young Adult
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
Brain infarction; Cerebrovascular disease; Familial hypercholesterolemia; Inherited dyslipidemia; Ischemic stroke; Statin treatment