Calcium Intake and Serum Calcium Level in Relation to the Risk of Ischemic Stroke: Findings from the REGARDS Study

다국어 초록 (Multilingual Abstract)

Background and Purpose Data on the association between calcium (Ca) and ischemic stroke are sparse and inconsistent. This study aimed to examine Ca intake and serum Ca levels in relation to risk of ischemic stroke.
Methods The primary analysis included 19,553 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. A subcohort was randomly selected to create a casecohort study (n=3,016), in which serum Ca levels were measured. Ischemic stroke cases were centrally adjudicated by physicians based on medical records. Cox proportional hazards regression for the cohort and weighted Cox proportional hazard regression with robust sandwich estimation method for the case-cohort analysis with adjustment for potential confounders were performed.
Results During a mean 8.3-year follow-up, 808 incident cases of ischemic stroke were documented.
Comparing the highest quintile to the lowest, a statistically significant inverse association was observed between total Ca intake and risk of ischemic stroke (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55 to 0.95; Plinear-trend=0.183); a restricted cubic spline analysis indicated a threshold effect like non-linear association of total Ca intake with ischemic stroke (Pnon-linear=0.006).
In the case-cohort, serum Ca was inversely associated with the risk of ischemic stroke. Compared to the lowest, the highest quintile of serum Ca had a 27% lower risk of ischemic stroke (HR, 0.73; 95% CI, 0.53 to 0.99; Plinear-trend=0.013). Observed associations were mainly mediated by type 2 diabetes, hypertension, and cholesterol.
Conclusions These findings suggest that serum Ca has inverse and Ca intake has threshold effect like association with risk of ischemic stroke.

참고문헌 (Reference)

1 Boucher B, "Validity and reliability of the Block98 food-frequency questionnaire in a sample of Canadian women" 9 : 84-93, 2006

2 Pittas AG, "The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis" 92 : 2017-2029, 2007

3 Howard VJ, "The reasons for geographic and racial differences in stroke study: objectives and design" 25 : 135-143, 2005

4 Jee SH, "The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials" 15 : 691-696, 2002

5 Hertzmark E, "The SAS MEDIATE Macro"

6 Li R, "The SAS LGTPHCURV9 Macro"

7 Ayaz O, "Testosterone modulates cardiac contraction and calcium homeostasis: cellular and molecular mechanisms" 6 : 9-, 2015

8 "Stroke: 1989. Recommendations on stroke prevention, diagnosis, and therapy. Report of the WHO task force on stroke and other cerebrovascular disorders" 20 : 1407-1431, 1989

9 Vatanparast H, "Socio-economic status and vitamin/mineral supplement use in Canada" 21 : 19-25, 2010

10 Judd SE, "Self-report of stroke, transient ischemic attack, or stroke symptoms and risk of future stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study" 44 : 55-60, 2013

11 Newby PK, "Race and region have independent and synergistic effects on dietary intakes in black and white women" 11 : 25-, 2012

12 Goltzman D, "Physiology of the calcium-parathyroid hormone-vitamin D axis" 50 : 1-13, 2018

13 Deb P, "Pathophysiologic mechanisms of acute ischemic stroke: an overview with emphasis on therapeutic significance beyond thrombolysis" 17 : 197-218, 2010

14 Guerrero-Romero F, "Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial" 30 : 253-258, 2004

15 Sánchez M, "Oral calcium supplementation reduces intraplatelet free calcium concentration and insulin resistance in essential hypertensive patients" 29 : 531-536, 1997

16 Sebastian RS, "Older adults who use vitamin/mineral supplements differ from nonusers in nutrient intake adequacy and dietary attitudes" 107 : 1322-1332, 2007

17 VanderWeele TJ, "Mediation analysis: a practitioner’s guide" 37 : 17-32, 2016

18 Sarrafzadegan N, "Magnesium status and the metabolic syndrome: a systematic review and meta-analysis" 32 : 409-417, 2016

19 Hardwick LL, "Magnesium absorption: mechanisms and the influence of vitamin D, calcium and phosphate" 121 : 13-23, 1991

20 Pikilidou MI, "Insulin sensitivity increase after calcium supplementation and change in intraplatelet calcium and sodium-hydrogen exchange in hypertensive patients with type 2 diabetes" 26 : 211-219, 2009

21 O’Neal WT, "Heart rate and ischemic stroke: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study" 10 : 1229-1235, 2015

22 Schulze MB, "Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and metaanalysis" 167 : 956-965, 2007

23 Shrira I, "Exposure to the US Stroke Buckle as a risk factor for cerebrovascular mortality" 30 : 229-233, 2008

24 Bucher HC, "Effects of dietary calcium supplementation on blood pressure. A meta-analysis of randomized controlled trials" 275 : 1016-1022, 1996

25 Kass L, "Effect of magnesium supplementation on blood pressure: a meta-analysis" 66 : 411-418, 2012

26 Bolland MJ, "Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis" 341 : c3691-, 2010

27 Howard VJ, "Disparities in stroke incidence contributing to disparities in stroke mortality" 69 : 619-627, 2011

28 Judd SE, "Dietary patterns are associated with incident stroke and contribute to excess risk of stroke in black Americans" 44 : 3305-3311, 2013

29 Liu S, "Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women" 28 : 2926-2932, 2005

30 Larsson SC, "Dietary calcium intake and risk of stroke: a dose-response meta-analysis" 97 : 951-957, 2013

31 Ross AC, "Dietary Reference Intakes for Calcium and Vitamin D" National Academies Press 35-74, 2011

32 Chrysant SG, "Controversy regarding the association of high calcium intake and increased risk for cardiovascular disease" 16 : 545-550, 2014

33 Subar AF, "Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires: the Eating at America’s Table Study" 154 : 1089-1099, 2001

34 Chowdhury R, "Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysi" 27 : 581-591, 2012

35 Bell L, "Cholesterol-lowering effects of calcium carbonate in patients with mild to moderate hypercholesterolemia" 152 : 2441-2444, 1992

36 Koton S, "Cerebral artery calcification in patients with acute cerebrovascular diseases: determinants and long-term clinical outcome" 19 : 739-745, 2012

37 Kulathinal S, "Case-cohort design in practice: experiences from the MORGAM Project" 4 : 15-, 2007

38 Bolland MJ, "Calcium supplements and cardiovascular risk: 5 years on" 4 : 199-210, 2013

39 Saito K, "Calcium supplementation attenuates an enhanced platelet function in saltloaded mildly hypertensive patients" 26 : 156-163, 1995

40 Anderson JJ, "Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10-year follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA)" 5 : e003815-, 2016

41 Tian DY, "Calcium intake and the risk of stroke: an up-dated meta-analysis of prospective studies" 24 : 245-252, 2015

42 Wang L, "Calcium intake and risk of cardiovascular disease: a review of prospective studies and randomized clinical trials" 12 : 105-116, 2012

43 Ikegame M, "Calcitonin-induced change in serum calcium levels and its relationship to osteoclast morphology and number of calcitonin receptors" 35 : 27-33, 2004

44 van Mierlo LA, "Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials" 20 : 571-580, 2006

45 Amalraj A, "Bioavailability of calcium and its absorption inhibitors in raw and cooked green leafy vegetables commonly consumed in India: an in vitro study" 170 : 430-436, 2015

46 Tao MH, "Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study" 6 : 105-113, 2015

47 Buck BH, "Association of higher serum calcium levels with smaller infarct volumes in acute ischemic stroke" 64 : 1287-1291, 2007

48 Aaron KJ, "Association of dietary sodium and potassium intakes with albuminuria in normal-weight, overweight, and obese participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study" 94 : 1071-1078, 2011

49 Rohrmann S, "Association between serum calcium concentration and risk of incident and fatal cardiovascular disease in the prospective AMORIS study" 251 : 85-93, 2016

50 Jensen-Otsu E, "Antidepressant use is associated with increased energy intake and similar levels of physical activity" 7 : 9662-9671, 2015

51 Barlow WE, "Analysis of casecohort designs" 52 : 1165-1172, 1999

52 Tsivgoulis G, "Adherence to a Mediterranean diet and prediction of incident stroke" 46 : 780-785, 2015

53 Block G, "A data-based approach to diet questionnaire design and testing" 124 : 453-469, 1986