Importance: Previous studies have shown lower cardiovascular risk with higher high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high HDL-C concentrations. Objective: To study the association between very high HDL-C levels (>80 mg/dL) and mortality in patients with coronary artery disease (CAD) and to investigate the association of known HDL-C genotypes with high HDL-C level outcomes. Design, Setting, and Participants: This prospective, multicenter, cohort study, conducted from 2006 to present in the UK and from 2003 to present in Atlanta, Georgia, recruited patients with CAD from the UK Biobank (UKB) and the Emory Cardiovascular Biobank (EmCAB), respectively. Patients without confirmed CAD were excluded from the study. Data analyses were conducted from May 10, 2020, to April 28, 2021. Exposure: High HDL-C levels (>80 mg/dL). Main Outcomes and Measures: The primary outcome was all-cause death. The secondary outcome was cardiovascular death. Results: A total of 14 478 participants (mean [SD] age, 62.1 [5.8] years; 11 034 men [76.2%]) from the UKB and 5467 participants (mean [SD] age, 63.8 [12.3] years; 3632 men [66.4%]) from the EmCAB were included in the study. Over a median follow-up of 8.9 (IQR, 8.0-9.7) years in the UKB and 6.7 (IQR, 4.0-10.8) years in the EmCAB, a U-shaped association with outcomes was observed with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (>80 mg/dL) were associated with increased risk of all-cause death (hazard ratio [HR], 1.96; 95% CI, 1.42-2.71; P < .001) and cardiovascular death (HR, 1.71; 95% CI, 1.09-2.68; P = .02) compared with those with HDL-C levels in the range of 40 to 60 mg/dL in the UKB after adjustment for confounding factors. These results were replicated in the EmCAB. These associations persisted after adjustment for the HDL-C genetic risk score within the UKB. Sensitivity analyses demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher among men than women in the UKB (HR, 2.63; 95% CI, 1.75-3.95; P < .001 vs HR, 1.39; 95% CI, 0.82-2.35; P = .23). Conclusions and Relevance: Results of this cohort study suggest that very high HDL-C levels are paradoxically associated with higher mortality risk in individuals with CAD. This association was independent of the common polymorphisms associated with high HDL-C levels.
Importance: Previous studies have shown lower cardiovascular risk with higher high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high HDL-C concentrations. Objective: To study the association between very high HDL-C levels (>80 mg/dL) and mortality in patients with coronary artery disease (CAD) and to investigate the association of known HDL-C genotypes with high HDL-C level outcomes. Design, Setting, and Participants: This prospective, multicenter, cohort study, conducted from 2006 to present in the UK and from 2003 to present in Atlanta, Georgia, recruited patients with CAD from the UK Biobank (UKB) and the Emory Cardiovascular Biobank (EmCAB), respectively. Patients without confirmed CAD were excluded from the study. Data analyses were conducted from May 10, 2020, to April 28, 2021. Exposure: High HDL-C levels (>80 mg/dL). Main Outcomes and Measures: The primary outcome was all-cause death. The secondary outcome was cardiovascular death. Results: A total of 14 478 participants (mean [SD] age, 62.1 [5.8] years; 11 034 men [76.2%]) from the UKB and 5467 participants (mean [SD] age, 63.8 [12.3] years; 3632 men [66.4%]) from the EmCAB were included in the study. Over a median follow-up of 8.9 (IQR, 8.0-9.7) years in the UKB and 6.7 (IQR, 4.0-10.8) years in the EmCAB, a U-shaped association with outcomes was observed with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (>80 mg/dL) were associated with increased risk of all-cause death (hazard ratio [HR], 1.96; 95% CI, 1.42-2.71; P < .001) and cardiovascular death (HR, 1.71; 95% CI, 1.09-2.68; P = .02) compared with those with HDL-C levels in the range of 40 to 60 mg/dL in the UKB after adjustment for confounding factors. These results were replicated in the EmCAB. These associations persisted after adjustment for the HDL-C genetic risk score within the UKB. Sensitivity analyses demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher among men than women in the UKB (HR, 2.63; 95% CI, 1.75-3.95; P < .001 vs HR, 1.39; 95% CI, 0.82-2.35; P = .23). Conclusions and Relevance: Results of this cohort study suggest that very high HDL-C levels are paradoxically associated with higher mortality risk in individuals with CAD. This association was independent of the common polymorphisms associated with high HDL-C levels.
Authors: Dennis T Ko; David A Alter; Helen Guo; Maria Koh; Geoffrey Lau; Peter C Austin; Gillian L Booth; William Hogg; Cynthia A Jackevicius; Douglas S Lee; Harindra C Wijeysundera; John T Wilkins; Jack V Tu Journal: J Am Coll Cardiol Date: 2016-11-08 Impact factor: 24.094
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Authors: Jørgen Jeppesen; Tine W Hansen; Michael H Olsen; Susanne Rasmussen; Hans Ibsen; Christian Torp-Pedersen; Per R Hildebrandt; Sten Madsbad Journal: Eur J Cardiovasc Prev Rehabil Date: 2008-10
Authors: Andrew S Levey; Lesley A Stevens; Christopher H Schmid; Yaping Lucy Zhang; Alejandro F Castro; Harold I Feldman; John W Kusek; Paul Eggers; Frederick Van Lente; Tom Greene; Josef Coresh Journal: Ann Intern Med Date: 2009-05-05 Impact factor: 25.391
Authors: Luís Meira-Machado; Carmen Cadarso-Suárez; Francisco Gude; Artur Araújo Journal: Comput Math Methods Med Date: 2013-12-12 Impact factor: 2.238
Authors: Martin J Landray; Richard Haynes; Jemma C Hopewell; Sarah Parish; Theingi Aung; Joseph Tomson; Karl Wallendszus; Martin Craig; Lixin Jiang; Rory Collins; Jane Armitage Journal: N Engl J Med Date: 2014-07-17 Impact factor: 91.245
Authors: Benjamin F Voight; Gina M Peloso; Marju Orho-Melander; Ruth Frikke-Schmidt; Maja Barbalic; Majken K Jensen; George Hindy; Hilma Hólm; Eric L Ding; Toby Johnson; Heribert Schunkert; Nilesh J Samani; Robert Clarke; Jemma C Hopewell; John F Thompson; Mingyao Li; Gudmar Thorleifsson; Christopher Newton-Cheh; Kiran Musunuru; James P Pirruccello; Danish Saleheen; Li Chen; Alexandre F R Stewart; Arne Schillert; Unnur Thorsteinsdottir; Gudmundur Thorgeirsson; Sonia Anand; James C Engert; Thomas Morgan; John Spertus; Monika Stoll; Klaus Berger; Nicola Martinelli; Domenico Girelli; Pascal P McKeown; Christopher C Patterson; Stephen E Epstein; Joseph Devaney; Mary-Susan Burnett; Vincent Mooser; Samuli Ripatti; Ida Surakka; Markku S Nieminen; Juha Sinisalo; Marja-Liisa Lokki; Markus Perola; Aki Havulinna; Ulf de Faire; Bruna Gigante; Erik Ingelsson; Tanja Zeller; Philipp Wild; Paul I W de Bakker; Olaf H Klungel; Anke-Hilse Maitland-van der Zee; Bas J M Peters; Anthonius de Boer; Diederick E Grobbee; Pieter W Kamphuisen; Vera H M Deneer; Clara C Elbers; N Charlotte Onland-Moret; Marten H Hofker; Cisca Wijmenga; W M Monique Verschuren; Jolanda M A Boer; Yvonne T van der Schouw; Asif Rasheed; Philippe Frossard; Serkalem Demissie; Cristen Willer; Ron Do; Jose M Ordovas; Gonçalo R Abecasis; Michael Boehnke; Karen L Mohlke; Mark J Daly; Candace Guiducci; Noël P Burtt; Aarti Surti; Elena Gonzalez; Shaun Purcell; Stacey Gabriel; Jaume Marrugat; John Peden; Jeanette Erdmann; Patrick Diemert; Christina Willenborg; Inke R König; Marcus Fischer; Christian Hengstenberg; Andreas Ziegler; Ian Buysschaert; Diether Lambrechts; Frans Van de Werf; Keith A Fox; Nour Eddine El Mokhtari; Diana Rubin; Jürgen Schrezenmeir; Stefan Schreiber; Arne Schäfer; John Danesh; Stefan Blankenberg; Robert Roberts; Ruth McPherson; Hugh Watkins; Alistair S Hall; Kim Overvad; Eric Rimm; Eric Boerwinkle; Anne Tybjaerg-Hansen; L Adrienne Cupples; Muredach P Reilly; Olle Melander; Pier M Mannucci; Diego Ardissino; David Siscovick; Roberto Elosua; Kari Stefansson; Christopher J O'Donnell; Veikko Salomaa; Daniel J Rader; Leena Peltonen; Stephen M Schwartz; David Altshuler; Sekar Kathiresan Journal: Lancet Date: 2012-05-17 Impact factor: 79.321
Authors: Clare Bycroft; Colin Freeman; Desislava Petkova; Gavin Band; Lloyd T Elliott; Kevin Sharp; Allan Motyer; Damjan Vukcevic; Olivier Delaneau; Jared O'Connell; Adrian Cortes; Samantha Welsh; Alan Young; Mark Effingham; Gil McVean; Stephen Leslie; Naomi Allen; Peter Donnelly; Jonathan Marchini Journal: Nature Date: 2018-10-10 Impact factor: 49.962