A systematic review and meta-analysis (21 studies, 23,613 genetically confirmed heterozygous FH patients, 3,489 cardiovascular events) showed independent associations between ASCVD and hypertension (effect size 0.41), male sex (0.33), smoking (0.32), Lp(a) (0.22), age (0.21), BMI (0.11), triglycerides (0.08) and LDL-C (0.02). Beyond intensive LDL lowering, aggressive management of classic risk factors — especially blood pressure and smoking — is essential to limit residual risk in this high-risk group.
A total of 21 studies were identified, involving 23,613 individual participants and 3489 prevalent cardiovascular events. The sex distribution was 47.2% male and 52.8% female. Most of the studies were conducted in European populations, representing 90.5% of the total. The meta-analysis found associations between ASCVD and hypertension (effect size 0.414; 95% CI: 0.346-0.482), male sex (0.334; 0.213-0.456), smoking (0.324; 0.203-0.445), lipoprotein(a) (0.219; 0.127-0.312), age (0.212; 0.161-0.264), body mass index (0.108; 0.028-0.188), triglycerides (0.084; 0.057-0.111) and LDL-C (0.015; 0.002-0.028).
This is the first systematic review and meta-analysis demonstrating that hypertension, male sex, smoking, lipoprotein(a), age, body mass index, triglycerides and LDL-C are significantly and independently associated with ASCVD in genetically confirmed patients with heterozygous FH. These data can inform risk stratification models and optimise therapy in such patients.
