Coronary artery calcification and cardiovascular events in familial and severe hypercholesterolemia: A systematic review and meta-analysis
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Objectives Coronary artery calcification (CAC) is heterogeneous in familial hypercholesterolemia (FH). Few studies have compared the prevalence of CAC in severe hypercholesterolemia (SH) to FH and evaluated the risk of atherosclerotic cardiovascular disease (ASCVD) events across CAC strata. We aimed to systematically assess the presence and burden of CAC and examine the risk of ASCVD events among those with FH and SH. Methods In this systematic review and meta-analysis, we included studies involving patients with clinically or genetically diagnosed heterozygous FH, and those with SH (defined as low-density lipoprotein cholesterol [LDL-C] ≥190 mg/dL) with complete data on CAC. We also assessed the risk of ASCVD events across CAC strata. Results A total of 19 studies ( n = 8509 individuals) were included (mean age: 52.8 [SD 10.3] years; 52.9% female; untreated LDL-C: 203.6 [SD 49.0] mg/dL). Participants with SH were older and had a higher prevalence of hypertension and smoking history but less statin use compared to those with FH. The pooled prevalence of CAC=0 was 44% (SH: 51% vs. FH: 39%, p = 0.05), while the prevalence of CAC 1–100 was 34% (SH: 36% vs. FH: 34%, p = 0.58) and 23% for CAC > 100 (SH: 14% vs. FH: 27%, p = 0.02). Individuals with CAC = 0 had a lower ASCVD event rate (per 1000 person-years) (2.06 [95% CI, 0.68–4.01]) compared to those with CAC > 0 (25.49 [95% CI, 18.14–34.02]) ( p < 0.001). Conclusion Those with SH had a higher prevalence of CAC = 0 and a lower prevalence of CAC > 100 than those with FH. The presence of CAC was associated with higher ASCVD event rates overall in those with SH or FH.
Institutions: Yale University, Universidade de São Paulo, Hospital Universitário da Universidade de São Paulo, Hospital São Paulo, Instituto do Coração - HCFMUSP, VA Connecticut Healthcare System, Houston Methodist, University of North Carolina at Chapel Hill, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, Inova Health System, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Fondation pour l’innovation en Cadiométabolisme et Nutrition, Universitat Pompeu Fabra, Hospital Del Mar, Hospital del Mar Research Institute, Johns Hopkins University, Johns Hopkins Medicine, Kanazawa University, Hospital Israelita Albert Einstein
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,900
Award: G4986583071
OpenAlex ID: W7213040342