Renato Quispe1,2, Seth Shay Martin1,2, Erin Donelly Michos1,2, Isha Lamba3, Roger Scott Blumenthal1,2, Anum Saeed4, Joao Lima2,5, Rishi Puri6, Sarah Nomura7, Michael Tsai7, John Wilkins8, Christie Mitchell Ballantyne9, Stephen Nicholls10, Steven Richard Jones1,2, Mohamed Badreldin Elshazly1,6. 1. Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA. 2. Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Department of Medicine, New York Presbyterian Hospital-Cornell, 525 East 68th Street, New York, NY, USA. 4. Department of Cardiovascular Medicine, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 5. Division of Radiology, Johns Hopkins University, Baltimore, MD, USA. 6. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA. 7. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA. 8. Division of Cardiology and the Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 9. Department of Cardiovascular Medicine, Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. 10. Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Melbourne, Australia.
Abstract
AIMS: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. METHODS AND RESULTS: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.34). Similar results were shown when examining discordance across clinical cutpoints. CONCLUSIONS: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. METHODS AND RESULTS: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.34). Similar results were shown when examining discordance across clinical cutpoints. CONCLUSIONS: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated. Published on behalf of the European Society of Cardiology. All rights reserved.
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