Beschreibung:
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<jats:bold>Background:</jats:bold>
While a self-reported family history of cardiovascular disease (CVD) is predictive of incident CVD, the genetic and clinical factors underlying this association remain poorly understood.
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<jats:bold>Methods:</jats:bold>
We performed a cross-sectional analysis of United Kingdom (UK) Biobank participants without preexisting coronary artery disease (CAD), with genetic, biochemical, and clinical characterization at baseline. Self-reported family history of heart disease (FHHD) was the primary outcome, while clinical (diabetes, hypertension, smoking, apolipoprotein B/A1 ratio, body mass index (BMI), C-reactive protein [CRP], lipoprotein(a) [Lp(a)]) and genetic risk factors for CVD (CAD polygenic risk score [PRS], heterozygous familial hypercholesterolemia [HeFH]) were exposures. Models were adjusted for age, sex and statin prescription. All features were considered together using multiple logistic regression, and population attributable risks were subsequently estimated.
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<jats:bold>Results:</jats:bold>
Among 124 203 individuals, 53 318 (42.9%) participants reported FHHD. In a multivariable model, FHHD was significantly enriched for morbid obesity (OR 1.14, CI 1.08-1.21), hypertension (OR 1.21, CI 1.17-1.24), apolipoprotein B/A1 ratio 5th vs 1st quintile (OR 1.24, CI 1.19-1.29), lipoprotein(a) >125 nmol/L (OR 1.20, CI 1.17-1.24), CAD PRS 10th vs 1st decile (OR 1.68, CI 1.59-1.77) and HeFH (OR 1.32, CI 1.09-1.60). PAR analyses indicated that 24.9% (CI 21.9-28.0%) of FHHD is explained by genetic factors alone, 17.2% (CI 15.0 -19.3%) is explained by clinical factors alone, and 34.3% (CI 31.0-37.7%) is explained by both genetic and clinical factors.
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<jats:bold>Conclusions:</jats:bold>
Both genetic and clinical risk factors, including several modifiable variables, significantly contribute to FHHD. Comprehensive assessment of contributing familial features may facilitate individual FHHD interpretation and risk reduction.
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<jats:p>Figure 1: Genetic and clinical factors contributing to FHHD</jats:p>
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