Yiyi Zhang1, Mark J Pletcher2, Eric Vittinghoff2, Autumn M Clemons3, David R Jacobs4, Norrina B Allen5, Alvaro Alonso6, Brandon K Bellows1, Elizabeth C Oelsner1, Adina Zeki Al Hazzouri3, Dhruv S Kazi7, Sarah D de Ferranti8, Andrew E Moran1. 1. Division of General Medicine, Columbia University Medical Center, New York, New York. 2. Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco. 3. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York. 4. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis. 5. Department of Preventive Medicine, Northwestern University, Chicago, Illinois. 6. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia. 7. Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 8. Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
Abstract
Importance: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease (CVD). Most observational studies on the association between LDL-C and CVD have focused on LDL-C level at a single time point (usually in middle or older age), and few studies have characterized long-term exposures to LDL-C and their role in CVD risk. Objective: To evaluate the associations of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age with incident CVD later in life. Design, Setting, and Participants: This cohort study analyzed pooled data from 4 prospective cohort studies in the US (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis). Participants were included if they had 2 or more LDL-C measures that were at least 2 years apart between ages 18 and 60 years, with at least 1 of the LDL-C measures occurring during middle age at 40 to 60 years. Data from 1971 to 2017 were collected and analyzed from September 25, 2020, to January 10, 2021. Exposures: Cumulative exposure to LDL-C, TWA LDL-C, and LDL-C slope from age 18 to 60 years. Main Outcomes and Measures: Incident coronary heart disease (CHD), ischemic stroke, and heart failure (HF). Results: A total of 18 288 participants were included in this study. These participants had a mean (SD) age of 56.4 (3.7) years and consisted of 10 309 women (56.4%). During a median follow-up of 16 years, 1165 CHD, 599 ischemic stroke, and 1145 HF events occurred. In multivariable Cox proportional hazards regression models that adjusted for the most recent LDL-C level measured during middle age and for other CVD risk factors, the hazard ratios for CHD were as follows: 1.57 (95% CI, 1.10-2.23; P for trend = .01) for cumulative LDL-C level, 1.69 (95% CI, 1.23-2.31; P for trend <.001) for TWA LDL-C level, and 0.88 (95% CI, 0.69-1.12; P for trend = .28) for LDL-C slope. No association was found between any of the LDL-C variables and ischemic stroke or HF. Conclusions and Relevance: This cohort study showed that cumulative LDL-C and TWA LDL-C during young adulthood and middle age were associated with the risk of incident CHD, independent of midlife LDL-C level. These findings suggest that past levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic CVD.
Importance: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease (CVD). Most observational studies on the association between LDL-C and CVD have focused on LDL-C level at a single time point (usually in middle or older age), and few studies have characterized long-term exposures to LDL-C and their role in CVD risk. Objective: To evaluate the associations of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age with incident CVD later in life. Design, Setting, and Participants: This cohort study analyzed pooled data from 4 prospective cohort studies in the US (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis). Participants were included if they had 2 or more LDL-C measures that were at least 2 years apart between ages 18 and 60 years, with at least 1 of the LDL-C measures occurring during middle age at 40 to 60 years. Data from 1971 to 2017 were collected and analyzed from September 25, 2020, to January 10, 2021. Exposures: Cumulative exposure to LDL-C, TWA LDL-C, and LDL-C slope from age 18 to 60 years. Main Outcomes and Measures: Incident coronary heart disease (CHD), ischemic stroke, and heart failure (HF). Results: A total of 18 288 participants were included in this study. These participants had a mean (SD) age of 56.4 (3.7) years and consisted of 10 309 women (56.4%). During a median follow-up of 16 years, 1165 CHD, 599 ischemic stroke, and 1145 HF events occurred. In multivariable Cox proportional hazards regression models that adjusted for the most recent LDL-C level measured during middle age and for other CVD risk factors, the hazard ratios for CHD were as follows: 1.57 (95% CI, 1.10-2.23; P for trend = .01) for cumulative LDL-C level, 1.69 (95% CI, 1.23-2.31; P for trend <.001) for TWA LDL-C level, and 0.88 (95% CI, 0.69-1.12; P for trend = .28) for LDL-C slope. No association was found between any of the LDL-C variables and ischemic stroke or HF. Conclusions and Relevance: This cohort study showed that cumulative LDL-C and TWA LDL-C during young adulthood and middle age were associated with the risk of incident CHD, independent of midlife LDL-C level. These findings suggest that past levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic CVD.
Authors: Thomas O'Toole; Michelle D Kelsey; Nishant P Shah; Robert W McGarrah; Neha J Pagidipati Journal: Curr Cardiol Rep Date: 2022-08-25 Impact factor: 3.955
Authors: So Mi Jemma Cho; Satoshi Koyama; Yunfeng Ruan; Kim Lannery; Megan Wong; Ezimamaka Ajufo; Hokyou Lee; Amit V Khera; Michael C Honigberg; Pradeep Natarajan Journal: JAMA Cardiol Date: 2022-09-28 Impact factor: 30.154
Authors: Miguel Cainzos-Achirica; Renato Quispe; Reed Mszar; Ramzi Dudum; Mahmoud Al Rifai; Raimund Erbel; Andreas Stang; Karl-Heinz Jöckel; Nils Lehmann; Sara Schramm; Börge Schmidt; Peter P Toth; Jamal S Rana; Joao A C Lima; Henrique Doria de Vasconcellos; Donald Lloyd-Jones; Parag H Joshi; Colby Ayers; Amit Khera; Michael J Blaha; Philip Greenland; Khurram Nasir Journal: J Am Heart Assoc Date: 2022-08-09 Impact factor: 6.106