Risk factors for cardiovascular disease in heterozygous familial hypercholesterolemia: A systematic review and meta-analysis

• Published in: Journal of clinical lipidology 2019-01, Vol.13 (1), p.15-30
• Main Authors: Akioyamen, Leo E., Genest, Jacques, Chu, Anna, Inibhunu, Happy, Ko, Dennis T., Tu, Jack V.
• Format: Article
• Language: English
• Subjects: Age Factors; Attributable risk; Cardiovascular disease; Cardiovascular Diseases - epidemiology; Cigarette Smoking; Familial hypercholesterolemia; Heterozygote; Humans; Hyperlipoproteinemia Type II - epidemiology; Hyperlipoproteinemia Type II - genetics; Meta-analysis; Risk Factors; Sex Factors; Systematic review
• ISSN: 1933-2874; 1876-4789
• DOI: 10.1016/j.jacl.2018.10.012

Current data from individual studies present conflicting evidence about the relationship between risk factors and cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (FH). We conducted a systematic review and meta-analysis to quantify the association between various CVD risk factors and CVD in FH. We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed for English-language studies reporting adjusted-associations between cardiovascular, behavioral, or clinical risk factors and CVD with ≥ 100 participants. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) for selected risk factors with random-effects meta-analysis, from which we derived attributable risk estimates. We identified 27 studies representing 41,831 unique participants and 6629 CVD events. Age (OR: 1.07; 95% CI: 1.03, 1.10), male sex (OR: 1.95; 95% CI: 1.68, 2.23), hypertension (OR: 2.11; 95% CI: 1.64, 2.58), diabetes (OR: 1.95; 95% CI: 1.33, 2.57), body mass index (OR: 1.04; 95% CI: 1.03, 1.05), smoking (OR: 1.71; 95% CI: 1.30, 2.12), elevated lipoprotein(a) (OR: 1.90; 95% CI: 1.10, 2.71), low high-density lipoprotein cholesterol (OR: 1.39; 95% CI: 1.24, 1.53), and a family history of CVD (OR: 1.83, 95% CI: 1.58, 2.07) were found to be significant CVD risk factors in FH. Smoking, hypertension, and diabetes accounted for more than a quarter of CVD risk in FH individuals, whereas low-density lipoprotein cholesterol > 4.0 mmol/L accounted for 1 in 3 CVD cases. Meta-regression analyses found associations between low-density lipoprotein cholesterol (P = .045) and total cholesterol (P  4.0 mmol/L was associated with 1 in 3 CVD cases.