A Reverse J-Shaped Association Between Serum 25-Hydroxyvitamin D and Cardiovascular Disease Mortality: The CopD Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 100; no. 6; pp. 2339 - 2346
• Main Authors: Durup, Darshana, Jørgensen, Henrik Løvendahl, Christensen, Jane, Tjønneland, Anne, Olsen, Anja, Halkjær, Jytte, Lind, Bent, Heegaard, Anne-Marie, Schwarz, Peter
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.06.2015; Copyright by The Endocrine Society
• Subjects: 25-Hydroxyvitamin D; Adult; Aged; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - mortality; Cause of Death; Chronic obstructive pulmonary disease; Clinical trials; Denmark - epidemiology; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Myocardial infarction; Myocardial Infarction - blood; Myocardial Infarction - mortality; Serum levels; Stroke; Stroke - blood; Stroke - mortality; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - blood; Vitamin D Deficiency - blood; Vitamin D Deficiency - epidemiology; Women
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2014-4551

Context:Cardiovascular disease is the major cause of death in the Western world, but the association between 25-hydroxyvitamin D [25(OH)D] levels and the risk of cardiovascular disease mortality remains unclear.Objective:The objective of the study was to determine the association between cardiovascular, stroke, and acute myocardial infarct mortality and serum levels of 25(OH)D.Design:This was an observational cohort study, the Copenhagen vitamin D study, data from a single laboratory center in Copenhagen, Denmark. Follow-up was from 2004 to 2011.Setting:Serum 25(OH)D was analyzed from 247 574 subjects from the Copenhagen general practice sector.Participants:Examination of the association 25(OH)D levels and mortality from cardiovascular disease, stroke, and acute myocardial infarct was performed among 161 428 women and 86 146 men.Main Outcome Measures:A multivariate Cox regression analysis was used to compute hazard ratios for cardiovascular, stroke, and acute myocardial infarct mortality.Results:Of 247 574 subjects, a total of 16 645 subjects died in the ensuing 0–7 years. A total of 5454 died from cardiovascular disease including 1574 from stroke and 702 from acute myocardial infarct. The 25(OH)D level of 70 nmol/L was associated with the lowest cardiovascular disease mortality risk. Compared with that level, the hazard ratio for cardiovascular disease mortality was 2.0 [95% confidence interval (CI) 1.8–2.1] at the lower extreme (∼12.5 nmol/L) with a higher risk for men [2.5 (95% CI 2.2–2.9)] than for women [1.7 (95% CI 1.5–1.9)]. At the higher extreme (∼125 nmol/L), the hazard ratio of cardiovascular disease mortality was 1.3 (95% CI 1.2–1.4), with a similar risk among men and women. Results were similar for stroke and acute myocardial subgroups.Conclusions:In this large observational study, low and high levels of 25(OH)D were associated with cardiovascular disease, stroke, and acute myocardial mortality in a nonlinear, reverse J-shaped manner, with the highest risk at lower levels. Whether this was a causal or associational finding cannot be determined from our data. There is a need for randomized clinical trials that include information on the effects of 25(OH)D levels greater than 100 nmol/L.