{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:27:58Z","timestamp":1793831278203,"version":"4.6.1"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,8,2]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Current cholesterol guidelines have recommended very low low\u2010density lipoprotein cholesterol (LDL\u2010C) treatment targets for people at high risk of cardiovascular disease (CVD). However, recent observational studies indicated that very low LDL\u2010C levels may be associated with increased mortality and other adverse outcomes. The association between LDL\u2010C levels and long\u2010term risk of overall and cardiovascular mortality among the U.S. general population remains to be determined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">This prospective cohort study included a nationally representative sample of 14\u2009035 adults aged 18\u2009years or older, who participated in the National Health and Nutrition Examination Survey III 1988\u20131994. LDL\u2010C levels were divided into 6 categories: &lt;70, 70\u201399.9, 100\u2013129.9, 130\u2013159.9, 160\u2013189.9 and \u2265190\u00a0mg\/dL. Deaths and underlying causes of deaths were ascertained by linkage to death records through December 31, 2015. Weighted Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of mortality outcomes and its 95% CIs. During 304\u2009025 person\u2010years of follow up (median follow\u2010up 23.2\u2009years), 4458 deaths occurred including 1243 deaths from CVD. At baseline, mean age was 41.5\u2009years and 51.9% were women. Very low and very high levels of LDL\u2010C were associated with increased mortality. After adjustment for age, sex, race and ethnicity, education, socioeconomic status, lifestyle factors, C\u2010reactive protein, body mass index, and other cardiovascular risk factors, individuals with LDL\u2010C&lt;70\u00a0mg\/dL, compared to those with LDL\u2010C 100\u2013129.9\u00a0mg\/dL, had HRs of 1.45 (95% CI, 1.10\u20131.93) for all\u2010cause mortality, 1.60 (95% CI, 1.01\u20132.54) for CVD mortality, and 4.04 (95% CI, 1.83\u20138.89) for stroke\u2010specific mortality, but no increased risk of coronary heart disease mortality. Compared with those with LDL\u2010C 100\u2013129.9\u00a0mg\/dL, individuals with LDL\u2010C\u2265190\u00a0mg\/dL had HRs of 1.49 (95% CI, 1.09\u20132.02) for CVD mortality, and 1.63 (95% CI, 1.12\u20132.39) for coronary heart disease mortality, but no increased risk of stroke mortality.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Both very low and very high LDL\u2010C levels were associated with increased risks of CVD mortality. Very low LDL\u2010C levels was also associated with the high risks of all\u2010cause and stroke mortality. Further investigation is needed to elucidate the optimal range of LDL\u2010C levels for CVD health in the general population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.023690","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T11:22:07Z","timestamp":1659093727000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Association of Low\u2010Density Lipoprotein Cholesterol Levels with More than 20\u2010Year Risk of Cardiovascular and All\u2010Cause Mortality in the General Population"],"prefix":"10.1161","volume":"11","author":[{"given":"Shuang","family":"Rong","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene School of Public Health, Medical College, Wuhan University of Science and Technology Wuhan China"},{"name":"Academy of Nutrition and Health Wuhan University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benchao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene School of Public Health, Medical College, Wuhan University of Science and Technology Wuhan China"},{"name":"Academy of Nutrition and Health Wuhan University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5227-4236","authenticated-orcid":false,"given":"Liangkai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangbo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine University of Tennessee Health Science Center Memphis TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Epidemiology College of Public Health, University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology College of Public Health, University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer G.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology College of Public Health, University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-5786","authenticated-orcid":false,"given":"Wei","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology College of Public Health, University of Iowa Iowa City IA"},{"name":"Obesity Research and Education Initiative University of Iowa Iowa City IA"},{"name":"Fraternal Order of Eagles Diabetes Research Center University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034273"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.03.529"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32519-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.13260"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2016.4396"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31942-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.13985"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32332-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32290-0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy533"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007454"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007853"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101571"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.2525"},{"key":"e_1_3_2_16_2","first-page":"1","article-title":"Plan and operation of the Third National Health and Nutrition Examination Survey, 1988\u201394. 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