Association between serum calcium concentration and risk of incident and fatal cardiovascular disease in the prospective AMORIS study.
Previous epidemiological studies have shown positive associations between serum calcium concentration and risk of cardiovascular disease (CVD), but results differ by definition of CVD. We examined the association of circulating calcium with incident and fatal CVD, myocardial infarction (MI), and stroke in the Swedish AMORIS cohort.



We included 441,738 participants of the AMORIS database linked for follow-up information on morbidity and mortality. Concentrations of total calcium were fully automated measured using a colorimetric method; concentrations of albumin were measured with a bromocresol green method between 1985 and 1995. The association of albumin-corrected calcium concentration and risk of incident and fatal CVD, MI, and stroke, respectively, was assessed with multivariable adjusted Cox proportional hazards models.



Until December 31, 2011, during a median follow-up time of 21 years, 90,866 incident cases of CVD, 21,271 of MI, and 25,810 of stroke were identified. High serum calcium concentrations were associated with increased risk of non-fatal CVD (Hazard ratio [HR] = 1.12, 95% CI 1.10-1.14, top [≥2.40 nmol/L] vs. bottom [≤2-25 nmol/L] quintile), MI (1.19, 1.14-1.25), and stroke (1.11, 1.06-1.15) and fatal disease (CVD: 1.41, 1.35-1.47; MI: 1.41, 1.31-1.51; stroke: 1.30, 1.20-1.41). Effect modification by sex was observed for incident disease such that associations were stronger among women than men. Serum calcium was positively associated with both incident and fatal ischemic stroke and with fatal hemorrhagic stroke, but not with incident hemorrhagic stroke. In a sub-groups analysis, the results remained significant after adjustment for smoking.



The results support a modest positive association between serum calcium and risk of CVD, but the underlying mineral metabolism and the exact mechanisms are currently unclear.
Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute (EPBI), University of Zurich, Zurich, UK. Electronic address: sabine.rohrmann@uzh.ch.
Sabine
S
Rohrmann
Cancer Epidemiology Unit, Division of Cancer Studies, Kings College London, London, UK; Regional Cancer Centre, Uppsala University Hospital, Uppsala, Sweden.
Hans
H
Garmo
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Håkan
H
Malmström
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; AstraZeneca, Södertälje, Sweden.
Niklas
N
Hammar
Department of Medicine, Clinical Epidemiological Unit, Karolinska Institutet and CALAB Research, Stockholm, Sweden.
Ingmar
I
Jungner
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Göran
G
Walldius
Cancer Epidemiology Unit, Division of Cancer Studies, Kings College London, London, UK.
Mieke
M
Van Hemelrijck
D000328:Adult; D002118:Calcium / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis*; D015331:Cohort Studies; D003124:Colorimetry; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012709:Serum Albumin / Q000032:analysis; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology; D013548:Sweden; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D012709:Serum Albumin; D014280:Triglycerides; D002118:Calcium
Fatal myocardial infarction; Haemorrhagic stroke; Incidence; Ischaemic; Serum calcium