The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality

Clin Chem Lab Med. 2024 Jun 19;63(1):208-219. doi: 10.1515/cclm-2024-0391. Print 2025 Jan 29.

Abstract

Objectives: The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)2D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden.

Methods: 25(OH)D, 24,25(OH)2D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study.

Results: Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6 %) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50 nmol/L [20 ng/mL] (21.6 vs. 11.5 %). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7 %, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals.

Conclusions: Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.

Keywords: cardiovascular mortality; functional deficiency; vitamin D.

MeSH terms

  • Aged
  • Cardiovascular Diseases* / blood
  • Cardiovascular Diseases* / mortality
  • Female
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments
  • Vitamin D Deficiency* / blood
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / epidemiology
  • Vitamin D* / analogs & derivatives
  • Vitamin D* / blood

Substances

  • Vitamin D
  • Natriuretic Peptide, Brain
  • 25-hydroxyvitamin D
  • pro-brain natriuretic peptide (1-76)
  • Peptide Fragments