Introduction:
Serum concentrations of calcium and 25-hydroxyvitamin D [25(OH)D] may potentially contribute to the development of abdominal aortic aneurysms (AAA), likely predominately through established AAA risk factors such as hypertension and inflammation. To date, no prospective epidemiologic studies have examined the association between calcium and 25(OH)D and AAA risk.
Hypothesis:
We hypothesized that 20-year risk of AAA is higher among individuals with elevated serum calcium and among those with low serum of 25(OH)D.
Methods:
Serum calcium and 25(OH)D were measured in Atherosclerosis Risk in Communities (ARIC) study participants without prior AAA and who attended visit 2 (1990-92) (N=13,452). Serum calcium was corrected for serum albumin. AAA events were identified through 2011 via annual follow-up phone calls for hospitalized AAAs, and through Medicare for both hospitalized and outpatient AAAs. Multi-variable Cox proportional hazards models were used. Calcium was modeled as quartiles and 25(OH)D as <10, 10-<20, 20-<30, ≥30 ng/ml. Additionally, sex-stratified analysis was conducted.
Results:
The participants were mean±SD age 57±6y, 44% men and 75% white. Mean serum concentrations were 9.2±0.4 mg/dl for calcium and 24.3±8.5 ng/ml for 25(OH)D. Over a median 19.7 years of follow-up, 484 AAA cases were identified. High serum calcium was associated with an increased incidence of AAA [HR Q4 v Q1=1.60 (95% CI: 1.24-2.08)] after adjustment for demographics and with additional adjustment for height, weight and smoking [1.39 (1.05-1.82)], but not after other CVD risk factors were controlled for [1.20 (0.91-1.58)]. In the fully adjusted model, a sex-interaction was present [p-value sex*calcium interaction=0.03], whereby the association was present in women [2.28 (1.20-4.34)] not men [1.05 (0.75-1.47)]. Those with 25(OH)D ≥30 ng/ml vs. <10 ng/ml had a HR for AAA of 1.54 (1.03-2.29) after demographic adjustment, but the association was attenuated with further adjustment for height, weight and smoking [1.24 (0.82-1.88)]. No sex-25(OH)D interaction was detected. As such, stratified results are not presented.
Conclusions:
In this large prospective cohort, there was little evidence that markers of vitamin D metabolism are associated with risk of incident AAA. The positive association of calcium with AAA among women may warrant further investigation and replication in other populations.
The 25-hydroxyvitamin D3 C-3 epimer: Distribution, correlates, and reclassification of 25-hydroxyvitamin D status in the population-based Atherosclerosis Risk in Communities Study (ARIC)
