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Association Between Cumulative Low-Density Lipoprotein Cholesterol Exposure During Young Adulthood and Middle Age and Risk of Cardiovascular Events.

TitleAssociation Between Cumulative Low-Density Lipoprotein Cholesterol Exposure During Young Adulthood and Middle Age and Risk of Cardiovascular Events.
Publication TypeJournal Article
Year of Publication2021
AuthorsZhang Y, Pletcher MJ, Vittinghoff E, Clemons AM, Jacobs DR, Allen NB, Alonso A, Bellows BK, Oelsner EC, Hazzouri AZeki Al, Kazi DS, de Ferranti SD, Moran AE
JournalJAMA Cardiol
Date Published2021 12 01
KeywordsAdolescent, Adult, Cardiovascular Diseases, Cholesterol, LDL, Female, Follow-Up Studies, Humans, Hypolipidemic Agents, Incidence, Male, Middle Aged, Primary Prevention, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Young Adult

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="" ci="" p="" trend="" slope.="" no="" association="" was="" found="" between="" any="" of="" the="" variables="" 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.

Alternate JournalJAMA Cardiol
PubMed ID34550307
PubMed Central IDPMC8459309
Grant ListR01 HL107475 / HL / NHLBI NIH HHS / United States
K24 HL148521 / HL / NHLBI NIH HHS / United States
K23 HL130627 / HL / NHLBI NIH HHS / United States
R21 HL129924 / HL / NHLBI NIH HHS / United States
R01 HL141823 / HL / NHLBI NIH HHS / United States