Author + information
- Received June 26, 2018
- Revision received September 17, 2018
- Accepted September 20, 2018
- Published online September 2, 2019.
- Marcio H. Miname, MD, PhDa,
- Marcio Sommer Bittencourt, MD, PhD, MPHb,c,
- Sérgio R. Moraes, BSca,
- Rômulo I.M. Alves, BSca,
- Pamela R.S. Silva, PhDa,
- Cinthia E. Jannes, PhDa,
- Alexandre C. Pereira, MD, PhDa,
- José E. Krieger, MD, PhDa,
- Khurram Nasir, MD, MSc, MPHd and
- Raul D. Santos, MD, PhDa,e,∗ ()
- aHeart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil
- bHospital Israelita Albert Einstein & School of Medicine, Faculdade Israelita de Ciência da Saúde Albert Einstein, São Paulo, Brazil
- cCenter for Clinical and Epidemiological Research, University Hospital & São Paulo State Cancer Institute, University of São Paulo, São Paulo, Brazil
- dCenter for Outcomes Research and Evaluation and Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut
- eHospital Israelita Albert Einstein, São Paulo, Brazil
- ↵∗Address for correspondence:
Dr. Raul D. Santos, Heart Institute of São Paulo Medical School, Unidade Clínica de Lipides InCor HCFMUSP, Av. Dr Eneas C. Aguiar 44, CEP-05403-900, São Paulo, SP, Brazil.
Objectives The aim of this study was to evaluate the role of coronary artery calcium (CAC) as a predictor of atherosclerotic cardiovascular disease (ASCVD) (fatal or not myocardial infarction, stroke, unstable angina requiring revascularization, and elective myocardial revascularization) events in asymptomatic primary prevention molecularly proven heterozygous familial hypercholesterolemia (FH) subjects receiving standard lipid-lowering therapy.
Background FH is associated with premature ASCVD. However, the clinical course of ASCVD in subjects with FH is heterogeneous. CAC score, a marker of subclinical atherosclerosis burden, may optimize ASCVD risk stratification in FH.
Methods Subjects with FH underwent CAC measurement and were followed prospectively. The association of CAC with ASCVD was evaluated using multivariate analysis.
Results A total of 206 subjects (mean age 45 ± 14 years, 36.4% men, baseline and on-treatment low-density lipoprotein cholesterol 269 ± 70 mg/dl and 150 ± 56 mg/dl, respectively) were followed for a median of 3.7 years (interquartile range: 2.7 to 6.8 years). CAC was present in 105 (51%), and 15 ASCVD events (7.2%) were documented. Almost one-half of events were hard outcomes, and the others were elective myocardial revascularizations. The annualized rates of events per 1,000 patients for CAC scores of 0 (n = 101 [49%]), 1 to 100 (n = 62 [30%]) and >100 (n = 43 [21%]) were, respectively, 0, 26.4 (95% confidence interval: 12.9 to 51.8), and 44.1 (95% confidence interval, 26.0 to 104.1). In multivariate Cox regression analysis, log(CAC score + 1) was independently associated with incident ASCVD events (hazard ratio: 3.33; 95% CI: 1.635 to 6.790; p = 0.001).
Conclusions CAC was independently associated with ASCVD events in patients with FH receiving standard lipid-lowering therapy. This may help further stratify near-term risk in patients who might be candidates for further treatment with newer therapies.
- computed tomography
- coronary calcification
- familial hypercholesterolemia
- risk factors
Dr. Santos has received honoraria related to consulting, speaking, and research activities from Akcea, Amgen, AstraZeneca, Biolab, Esperion, Kowa, Merck, Novo-Nordisk, Pfizer, and Sanofi/Regeneron. Dr. Miname has received honoraria for speaking activities from Amgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 26, 2018.
- Revision received September 17, 2018.
- Accepted September 20, 2018.
- 2019 American College of Cardiology Foundation
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