Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study

Khurram Nasir; Reed Mszar; Miguel Cainzos-Achirica; Gowtham R Grandhi; Tycho R Tromp; Rodrigo Alonso; Márcio S Bittencourt; Eric Bruckert; José Luis Díaz-Díaz; Antonio Gallo; G Kees Hovingh; Marcio H Miname; Ovidio Muñiz-Grijalvo; Jing Pang; Leopoldo Perez de Isla; Eric J G Sijbrands; Gerald F Watts; Pedro Mata; Raul D Santos

doi:10.1016/j.ajpc.2023.100611

Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study

Am J Prev Cardiol. 2023 Nov 23:17:100611. doi: 10.1016/j.ajpc.2023.100611. eCollection 2024 Mar.

Authors

Khurram Nasir¹, Reed Mszar², Miguel Cainzos-Achirica³, Gowtham R Grandhi⁴, Tycho R Tromp⁵, Rodrigo Alonso^{6

7}, Márcio S Bittencourt⁸, Eric Bruckert⁹, José Luis Díaz-Díaz¹⁰, Antonio Gallo⁹, G Kees Hovingh⁵, Marcio H Miname¹¹, Ovidio Muñiz-Grijalvo¹², Jing Pang¹³, Leopoldo Perez de Isla¹⁴, Eric J G Sijbrands¹⁵, Gerald F Watts¹³, Pedro Mata⁷, Raul D Santos^{11

16}

Affiliations

¹ Houston Methodist DeBakey Heart & Vascular Center, Houston, TX, USA.
² Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
³ Department of Cardiology, Hospital del Mar / Parc de Salut Mar, Barcelona, Spain.
⁴ Virginia Commonwealth University Health Pauley Heart Center, Richmond, VA, USA.
⁵ Department of Vascular Medicine, Amsterdam UMC, location AMC, Amsterdam, the Netherlands.
⁶ Center for Advanced Metabolic Medicine and Nutrition, Santiago, Chile.
⁷ Fundación Hipercolesterolemia Familiar, Madrid, Spain.
⁸ Division of Internal Medicine, University Hospital, University of São Paulo, São Paulo, Brazil.
⁹ Sorbonne Université, INSERM UMR1166, Lipidology and Cardiovascular Prevention Unit, Department of Nutrition, APHP, Hôpital Pitié-Salpètriêre, Paris, France.
¹⁰ Complejo Hospitalario Universitario, Hospital Abente y Lago, A Corūna, Spain.
¹¹ Heart Institute (INCOR), University of São Paulo Medical School Hospital, São Paulo, Brazil.
¹² Internal Medicine Department, Hospital Virgen del Rocío, Sevilla, Spain.
¹³ School of Medicine, University of Western Australia, Department of Cardiology, Royal Perth Hospital, Western Australia, Australia.
¹⁴ Cardiology Department, Hospital Clinico San Carlos, IDISSC, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
¹⁵ Department of Internal Medicine, Section Pharmacology, Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.
¹⁶ Hospital Israelita Albert Einstein, São Paulo, Brazil.

Abstract

Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline.

Methods: We pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1-100, 101-400, >400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD).

Results: Ninety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1-100, 160 (16%) had CAC 101-400, and 99 (10%) had CAC >400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1-100 (8% [n = 15] vs 18% [n = 26]), CAC 101-400 (32% [n = 22] vs 40% [n = 36]), and CAC >400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50-59 years were less likely to have obstructive CAD in CAC >400 (55% [n = 6] vs 70% [n = 19]).

Conclusion: In this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.

Keywords: Atherosclerotic cardiovascular disease; Coronary artery calcium; Familial hypercholesterolemia; Low-density lipoprotein cholesterol; Plaque burden.