Disease Markers

Review Article

Optimal Vitamin D Supplementation Levels for Cardiovascular Disease Protection

Table 2

Key studies in vitamin D and cardiovascular disease.


Disease	Study	Design	Number of participants	Outcome

Hypertension	Scragg et al. (2007) [22]	Cross-sectional, observational	12,644	Vitamin D status is inversely associated with BP.
	Beveridge et al. (2015) [26]	Meta-analysis of 46 RCTs	4541	No effect of Vitamin D supplementation on systolic or diastolic BP.
	Forman et al. (2013) [27]	RCT	283	Dose dependent reduction in systolic BP.
	Dong et al. (2010) [28]	RCT	49	Reduction in arterial stiffness in young African-Caribbean subjects.

Heart failure	Zittermann et al. (2003) [34]	Observational	88	Chronic heart failure is more common in groups with low vitamin D.
	van Ballegooijen et al. (2013) [35]	Cross-Sectional, observational	969	Higher PTH was associated with greater left ventricular mass and lower systolic function.
	Kestenbaum et al. (2011) [36]	Observational	2,312	Vitamin D deficiency is associated with MI, mortality, and excess PTH with heart failure.
	Saleh et al. (2003) [37]	Observational	2,700	PTH is associated with left ventricular mass.
	Shedeed (2012) [38]	RCT	80	Supplementation improved cardiac function and decreased PTH and inflammatory markers.
	Schleithoff et al. (2006) [39]	RCT	93	Supplementation reduced inflammatory mediators and parathyroid hormone.
	Gotsman et al. (2012) [40]	Observational	49,834	Vitamin D deficiency highly prevalent and predictive of reduced survival.

Atrial fibrillation	Frost et al. (2002) [42]	Retrospective, observational	32,992	Seasonal variation in AF incidence, showing a winter peak and summer trough.
	Murphy et al. (2004) [43]	Retrospective, observational	68,045	Winter peak of hospitalizations with AF, with higher winter mortality.
	Reinstra et al. (2011) [44]	Retrospective, observational	2,930	Vitamin D is not associated with AF.
	Qayyum et al. (2012) [45]	Observational	258	Vitamin D is not associated with AF, stroke, or MI.
	Demir et al. (2014) [46]	Case-control	298	Vitamin D is associated with nonvalvular AF.
	Chen et al. (2014) [47]	Case-control	162	Association with AF and vitamin D deficiency are shown.
	Ozcan et al. (2015) [48]	Case-control	227	Vitamin D deficiency was associated with new-onset AF.

Coronary artery disease	Thomas et al. (2012) [50]	Cohort	1,801	Reduced all-cause and cardiovascular mortality and heart failure but not MI.
	Wang et al. (2008) [51]	Cohort	1,739	Higher risk of cardiovascular events with lower vitamin D levels.
	Oz et al. (2013) [52]	Cross-sectional, observational	222	Vitamin D deficiency associated with slow coronary flow, endothelial dysfunction, and subclinical atherosclerosis.
	Liew et al. (2015) [53]	Observational	375	Low vitamin D associated with worse angiographic CAD, nonarterial stiffness, or PVD.
	Ford et al. (2014) [54]	RCT	5,292	Vitamin D is protective against heart failure but not MI and stroke.

Stroke	Witham et al. (2012) [59]	RCT	58	High dose of vitamin D improved endothelial function in stroke patients with controlled BP.
	Hsia et al. (2007) [60]	RCT	36,282	No observed changes in coronary or stroke risk.
	Avenell et al. (2012) [61]	RCT	5,292	No effect on mortality, vascular disease, cancer mortality, or cancer incidence.
	Trivedi et al. (2003) [62]	RCT	2,686	Fractures may be reduced by supplementation but no change in stroke risk.

Peripheral vascular disease	Anderson et al. (2010) [63]	Retrospective, observational	41,504	Vitamin D deficiency associated with diabetes, hyperlipidemia, HTN, CAD, PVD, MI, and stroke.
	Melamed et al. (2008) [64]	Retrospective, observational	4,839	Low vitamin D is associated with higher PVD.
	Fahrleitner et al. (2002) [65]	Cross-sectional, observational	327	PVD is associated with vitamin D deficiency, secondary hyperparathyroidism, and osteomalacia.
	McDermott et al. (2014) [67]	Observational	658	Lower vitamin D levels associated with faster decline in walking in those with PVD.

Mortality	Zittermann et al. (2012) [68]	Meta-analysis of prospective cohorts	62,548	Nonlinear decrease in mortality for increased vitamin D levels, plateauing around 87.5 nmol/L.
	Johansson et al. (2012) [69]	Observational	2,878	In elderly men, low vitamin D levels are associated with increased mortality.
	Elamin et al. (2011) [70]	Meta-analysis of 51 RCTs	51 RCTs	No evidence of significant reduction in mortality or cardiovascular risk.
	Rejnmark et al. (2012) [71]	Meta-analysis of 8 major trials	70,528	Vitamin D with calcium reduced overall mortality.
	Bjelakovic et al. (2014) [72]	Meta-analysis of 56 RCTs	95,286	Vitamin D3 seemed to decrease mortality in elderly people.

BP, blood pressure; PTH, parathyroid hormone; AF, atrial fibrillation; MI, myocardial infarction; CAD, coronary artery disease; PVD, peripheral vascular disease; HTN, hypertension; RCT, randomised controlled trial.