{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:44:09Z","timestamp":1791200649709,"version":"4.2.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38\u2009153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81\u20130.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72\u20130.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels &lt;50 mg\/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94\u20131.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90\u20130.97).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.113.002670","type":"journal-article","created":{"date-parts":[[2013,8,21]],"date-time":"2013-08-21T23:41:27Z","timestamp":1377128487000},"page":"1504-1512","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":178,"title":["Levels and Changes of HDL Cholesterol and Apolipoprotein A-I in Relation to Risk of Cardiovascular Events Among Statin-Treated Patients"],"prefix":"10.1161","volume":"128","author":[{"given":"S. Matthijs","family":"Boekholdt","sequence":"first","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit J.","family":"Arsenault","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Kees","family":"Hovingh","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Mora","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje R.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"LaRosa","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.M.A.","family":"Welch","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Amarenco","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"DeMicco","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Tonkin","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"Kirby","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Colhoun","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham A.","family":"Hitman","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. John","family":"Betteridge","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul N.","family":"Durrington","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Clearfield","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Downs","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Antonio M.","family":"Gotto","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Ridker","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.P.","family":"Kastelein","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women\u2019s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(80)90516-0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1619"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.07.086"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.16.1893"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa064278"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60312-2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60713-1"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2011-301405"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b92"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107579"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706628"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206797"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.366"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(98)00131-0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_3_4_18_2","first-page":"1383","article-title":"Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).","volume":"344","author":"Scandinavian Simvastatin Survival Study Group","year":"1994","unstructured":"Scandinavian Simvastatin Survival Study Group. 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