{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:00:26Z","timestamp":1785578426440,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,29]]},"group-title":"Epidemiology","reference-count":26,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cumulative exposure to risk factor levels may capture cardiovascular disease (CVD) risk independent of a single measurement. We examined the association between cumulative exposure to systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and fasting plasma glucose (FPG) with CVD events among African American participants in the Jackson Heart Study (JHS).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We included all JHS participants with SBP, LDL-C, and FPG measurements at Exams 1 (2000-2004) and 3 (2009-2013) who were alive at 8 years of follow-up after Exam 1. We calculated 8-year cumulative exposures as the area under the trajectory of each risk factor using all available measurements from Exams 1, 2, and 3. Adjudicated coronary heart disease (CHD), stroke, and heart failure (HF) events after the 8-year exposure period and through December 31, 2016 were evaluated separately using conditional Cox regression models with each cumulative exposure, respective values at 8 years, and Exam 1 covariates as independent variables. Models were conducted separately for each risk factor, and exposures were centered and scaled for comparability.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 3188 eligible JHS participants, mean age was 54 years, and 64% were women. Higher cumulative exposures to SBP and LDL-C were associated with CHD events after adjustment for covariates and the 8-year values [adjusted hazard ratios (aHR) per SD: 1.37 per 136 mmHg-years of SBP (95% CI: 1.09, 1.71), and 1.56 per 309 mg\/dL-years of LDL-C (95% CI: 1.02, 2.37)]. Higher cumulative exposure to SBP and FPG were associated with HF events after adjustment [aHR: 1.15 per 136 mmHg-years of SBP (95% CI: 1.04, 1.27) and 1.10 per 262 mg\/dL-years of FPG (95% CI: 1.02, 1.18)]. Only the 8-year values, but not cumulative exposures, were associated with stroke risk after full adjustment.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Cumulative exposure to risk factors may provide additional information on CVD risk compared with single measurements later in life, particularly for CHD and HF events.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s1\">\n                  <jats:title>Clinical Perspective<\/jats:title>\n                  <jats:sec id=\"s1a\">\n                    <jats:title>What is new?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>We examined associations between cardiovascular risk factors (systolic blood pressure [SBP], low density lipoprotein cholesterol [LDL-C], fasting plasma glucose [FPG]) and coronary heart disease (CHD), heart failure (HF), and stroke in a population of African American adults.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>We calculated cumulative exposures as the area under the trajectory of each risk factor over 8 years and compared associations with a single value measured at the end of the exposure period.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Cumulative exposure to SBP, LDL-C and FPG conferred additional risk for CHD and HF events over single values.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                  <jats:sec id=\"s1b\">\n                    <jats:title>What are the clinical implications?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Long-term exposure to both clinical and subclinical levels of risk factors may improve comprehensive CVD risk assessment in African-American adults.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>These findings emphasize the importance of regular monitoring and sustained low levels of SBP, LDL-C, and FPG to manage lifetime CVD risk.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Interventions aimed at lowering and managing exposure to risk factors over the life course rather than solely treating risk factors once they are high, may represent effective strategies for reducing the burden of CVD in African American adults.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.27.26359076","type":"posted-content","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:30:12Z","timestamp":1785339012000},"source":"Crossref","is-referenced-by-count":0,"title":["Cumulative exposure to risk factors and subsequent cardiovascular disease events: The Jackson Heart Study"],"prefix":"10.64898","author":[{"given":"Rishi V.","family":"Parikh","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Muntner","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL"},{"name":"Perisphere Real World Evidence LLC. Austin, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9211-0474","authenticated-orcid":false,"given":"Shakia T.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4083-8328","authenticated-orcid":false,"given":"Mario","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, Population and Public Health, University of California at Riverside School of Medicine, Riverside, CACA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2470-0004","authenticated-orcid":false,"given":"Yuan-I","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Mississippi Medical Center, Jackson, MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6740-3002","authenticated-orcid":false,"given":"Kendra D.","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Reeves","sequence":"additional","affiliation":[{"name":"Insitute for Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-3648","authenticated-orcid":false,"given":"Michelle C.","family":"Odden","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026080102450598000_2026.07.27.26359076v1.1","unstructured":"2019 ACC\/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines | Circulation [Internet]. 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