Age, diabetes, body mass index, smoking, elevated lipoprotein(a), low high-density lipoprotein cholesterol (HDL-C) (at 4.0 mmol/L), and family history of cardiovascular disease (CVD) are all significant CVD risk factors in heterozygous familial hypercholesterolemia (FH), according to a review published in Journal of Clinical Lipidology.

Researchers conducted a systematic literature review and meta-analysis of studies to quantify associations between key CVD risk factors in FH. MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed were searched to identify relevant studies published between 1990 and January 2018. Additional studies were identified by reviewing reference lists within all the included articles and relevant literature reviews, systematic reviews, and meta-analyses.

Studies were reviewed if they had ≥100 participants (50 with CVD and 50 without) and reported adjusted associations between cardiovascular, behavioral, or clinical risk factors and CVD.

Studies were included in the review if they reported 2 types of key findings: 1) relative risk measures for CVD (hazard ratios, relative risks, and odds ratios [ORs]) associated with a predictive factor and a corresponding measure of variability and 2) associations between CVD in individuals with FH and traditional cardiovascular risk factors, health behaviors, or clinical and biochemical characteristics.

Meta-analyses were conducted by deriving ORs and 95% confidence intervals (CIs) for each risk association using a DerSimonian and Laird random-effects model. Estimations of attributable risk were calculated using the pooled ORs.

Upon screening 4025 unique reports, 78 were evaluated. After applying the exclusion criteria, 27 articles were included in the systematic review.

Based on the pooled ORs, significant risk factors for CVD in the population with FH were found as follows: 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), a positive family history of CVD (OR, 1.83; 95% CI, 1.58-2.07), elevated lipoprotein(a) (OR, 1.90; 95% CI, 1.10-2.71), and low HDL-C (<1 mmol/L; OR, 1.39; 95% CI, 1.24-1.53).

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The researchers noted several limitations to their review, such as the fact that relevant studies may have been missed for inclusion and that high levels of heterogeneity across their analyses.

The researchers explained, however, that this high level of heterogeneity could increase the generalizability of their meta-analyses.

The findings do suggest that in managing a patient with FH, “it is insufficient to simply classify people as diseased or not diseased.”

“An individual’s risk seems dependent on a number of known and modifiable risk factors,” the authors concluded.

Reference

Akioyamen LE, Genest J, Chu A, Inibhunu H, Ko DT, Tu JV. Risk factors for cardiovascular disease in heterozygous familial hypercholesterolemia: A systematic review and meta-analysis [published online November 7, 2018]. J Clin Lipidol. doi:10.1016/j.jacl.2018.10.012