Association of desphospho-uncarboxylated matrix gla protein with incident cardiovascular disease and all-cause mortality: Results from the prospective Bruneck Study. (July 2022)

• Record Type: Journal Article
• Authors: Willeit, Karin; Santer, Peter; Tschiderer, Lena; Pechlaner, Raimund; Vermeer, Cees; Willeit, Johann; Kiechl, Stefan
• Is Part Of: Atherosclerosis. Volume 353(2022)
• Page Start: 20
• Page End: 27
• Publication Date: 2022-07
• Subjects: Matrix gla protein -- Cardiovascular disease -- Mortality -- Prospective studies; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2022.06.1017
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: Matrix Gla protein (MGP), a vitamin K-dependent protein, is a potent inhibitor of vascular calcification. Desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K insufficiency, has been shown to predict cardiovascular disease (CVD) and all-cause mortality in high-risk populations. Whether the increased risk associated with dp-ucMGP also applies to the general, and especially, the elderly population has not yet been fully elucidated. Methods and results: Plasma dp-ucMGP was measured in 684 individuals aged 50–89 years of the prospective population-based Bruneck Study (baseline evaluation in 2000). Baseline median dp-ucMGP was 478.4 (IQR 335.0–635.2) pmol/L. Over a median follow-up of 15.5 years, 163 CVD events occurred and 235 participants died. Age-/sex-adjusted hazard ratios (HRs) per 1-SD higher level of loge transformed dp-ucMGP were 1.30 (95%CI: 1.09–1.55; p= 0.004) for incident CVD and 1.36 (95%CI: 1.17–1.57; p< 0.001) for all-cause mortality. After multivariable adjustment, the associations remained significant with HRs of 1.23 (95%CI: 1.02–1.47, p= 0.029) for CVD and 1.40 (95%CI: 1.20–1.64; p< 0.001) for all-cause mortality. The associations remained virtually unchanged after additional adjustment for dietary quality as measured with the Alternative Healthy Eating Index. We found no association of dp-ucMGP with myocardial infarction and sudden cardiac deaths, but a strong association with other vascular deaths and non-vascular/non-cancer deaths. Conclusions: This study shows a significant association of plasma dp-ucMGP with incident CVD and a significant and even stronger association with all-cause mortality. Clinical trials are needed to investigate whether vitamin K substitution results in improved health outcomes. Graphical abstract: Image 1 Highlights: Dp-ucMGP is a marker of vitamin K insufficiency resulting in impaired inhibition of vascular calcification. Dp-ucMGP was associated with future cardiovascular disease events and all-cause mortality. Dp-ucMGP was associated with vascular deaths and non-vascular/non-cancer deaths. Dp-ucMGP was not associated with myocardial infarction and sudden cardiac deaths. Clinical trials are warranted to examine whether vitamin K substitution results in improved health outcomes.