{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:47:20Z","timestamp":1787496440547,"version":"build-2736575974"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2016,7,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Heterozygous familial hypercholesterolemia (FH) affects up to 1 in 200 individuals in the United States, but atherosclerotic cardiovascular disease (ASCVD) outcomes of FH in the general US population have not been described. We therefore sought to evaluate long-term coronary heart disease (CHD) and total ASCVD risks in US adults with an FH phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Using individual pooled data from 6 large US epidemiological cohorts, we stratified participants by low-density lipoprotein cholesterol level at index ages from 20 to 79 years. For the primary analysis, low-density lipoprotein cholesterol levels \u2265190 and &lt;130 mg\/dL defined the FH phenotype and referent, respectively. Sensitivity analyses evaluated the effects of varying the FH phenotype definition. We used Cox regression models to assess covariate-adjusted associations of the FH phenotype with 30-year hazards for CHD (CHD death or nonfatal myocardial infarction) and total ASCVD (CHD or stroke).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We included 68\u2009565 baseline person-examinations; 3850 (5.6%) had the FH phenotype by the primary definition. Follow-up across index ages ranged from 78\u2009985 to 308\u2009378 person-years. After covariate adjustment, the FH phenotype was associated with substantially elevated 30-year CHD risk, with hazard ratios up to 5.0 (95% confidence interval, 1.1\u201321.7). Across index ages, CHD risk was accelerated in those with the FH phenotype by 10 to 20 years in men and 20 to 30 years in women. Similar patterns of results were found for total ASCVD risk, with hazard ratios up to 4.1 (95% confidence interval, 1.2\u201313.4). Alternative FH phenotype definitions incorporating family history, more stringent age-based low-density lipoprotein cholesterol thresholds, or alternative lipid fractions decreased the FH phenotype prevalence to as low as 0.2% to 0.4% without materially affecting CHD risk estimates (hazard ratios up to 8.0; 95% confidence interval, 1.0\u201361.6).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In the general US population, the long-term ASCVD burden related to phenotypic FH, defined by low-density lipoprotein cholesterol \u2265190 mg\/dL, is likely substantial. Our finding of CHD risk acceleration may aid efforts in risk communication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.116.022335","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T19:19:21Z","timestamp":1467227961000},"page":"9-19","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":186,"title":["Long-Term Risk of Atherosclerotic Cardiovascular Disease in US Adults With the Familial Hypercholesterolemia Phenotype"],"prefix":"10.1161","volume":"134","author":[{"given":"Amanda M.","family":"Perak","sequence":"first","affiliation":[{"name":"From Division of Cardiology, Department of Pediatrics, Ann &amp; Robert H. Lurie Children\u2019s Hospital of Chicago (A.M.P.), Department of Preventive Medicine (A.M.P., H.N., J.T.W., D.M.L.-J.), and Division of Cardiology, Department of Medicine (J.T.W., D.M.L.-J.), Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, MA (S.D.d.F.); and Division of Adolescent and Young Adult Medicine, Boston Children\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Ning","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Pediatrics, Ann &amp; Robert H. Lurie Children\u2019s Hospital of Chicago (A.M.P.), Department of Preventive Medicine (A.M.P., H.N., J.T.W., D.M.L.-J.), and Division of Cardiology, Department of Medicine (J.T.W., D.M.L.-J.), Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, MA (S.D.d.F.); and Division of Adolescent and Young Adult Medicine, Boston Children\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah D.","family":"de Ferranti","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Pediatrics, Ann &amp; Robert H. Lurie Children\u2019s Hospital of Chicago (A.M.P.), Department of Preventive Medicine (A.M.P., H.N., J.T.W., D.M.L.-J.), and Division of Cardiology, Department of Medicine (J.T.W., D.M.L.-J.), Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, MA (S.D.d.F.); and Division of Adolescent and Young Adult Medicine, Boston Children\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly C.","family":"Gooding","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Pediatrics, Ann &amp; Robert H. Lurie Children\u2019s Hospital of Chicago (A.M.P.), Department of Preventive Medicine (A.M.P., H.N., J.T.W., D.M.L.-J.), and Division of Cardiology, Department of Medicine (J.T.W., D.M.L.-J.), Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, MA (S.D.d.F.); and Division of Adolescent and Young Adult Medicine, Boston Children\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Pediatrics, Ann &amp; Robert H. Lurie Children\u2019s Hospital of Chicago (A.M.P.), Department of Preventive Medicine (A.M.P., H.N., J.T.W., D.M.L.-J.), and Division of Cardiology, Department of Medicine (J.T.W., D.M.L.-J.), Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, MA (S.D.d.F.); and Division of Adolescent and Young Adult Medicine, Boston Children\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald M.","family":"Lloyd-Jones","sequence":"additional","affiliation":[{"name":"From Division of Cardiology, Department of Pediatrics, Ann &amp; Robert H. Lurie Children\u2019s Hospital of Chicago (A.M.P.), Department of Preventive Medicine (A.M.P., H.N., J.T.W., D.M.L.-J.), and Division of Cardiology, Department of Medicine (J.T.W., D.M.L.-J.), Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, MA (S.D.d.F.); and Division of Adolescent and Young Adult Medicine, Boston Children\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.018791"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2014.09.001"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13917"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.a2423"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(98)00200-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn422"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.08.038"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht273"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","unstructured":"deGoma EM Ahmad ZS O\u2019Brien EC Kindt I Shrader P Newman CB Pokharel Y Baum SJ Hemphill LC Hudgins LC Ahmed CD Gidding SS Duffy D Neal W Wilemon K Roe MT Rader DJ Ballantyne CM Linton MF Duell PB Shapiro MD Moriarty PM Knowles JW. 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