A Negative Association between Plasma Phylloquinone and All-Cause Mortality in Chinese Adults with Hypertension: A Nested Case-Control Study

Abstract

Background: Previous studies have revealed that vitamin K is essential for preventing various chronic diseases. Phylloquinone is the primary dietary and circulating form of vitamin K. However, data concerning the association between plasma phylloquinone and all-cause mortality are limited.

Objectives: This study aimed to evaluate the association between plasma phylloquinone and risk of all-cause mortality and examine some potential confounders.

Methods: This study is a post hoc analysis of the RCT and a nested, case-control design was used. Enrolled participants had to have hypertension at baseline. Study initiation was 19 May, 2008, and the median follow-up was 4.5 y. A total of 604 mortality cases and 604 controls matched for age, sex, treatment group, and study site were included in this study. Odds ratios (OR) and 95% confidence intervals (CIs) of all-cause mortality were calculated using conditional or unconditional logistic regression, without or with adjusting for pertinent covariates, respectively. The concentration of phylloquinone was measured by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS).

Results: The mean and median phylloquinone levels were 1.62 nmol/L and 0.89 nmol/L, respectively. There was a significant negative association between log-transformed plasma phylloquinone and all-cause mortality after controlling for potential confounders (per 1 unit increase-OR: 0.79; 95% CI: 0.66, 0.95). Furthermore, the association of plasma phylloquinone with risk of all-cause mortality differed by body mass index (BMI) (<25 kg/m² compared with ≥25 kg/m², P-interaction = 0.004). A significant trend of decreasing risk with increasing concentration of phylloquinone was observed in participants with higher BMI (per 1 unit increase-OR: 0.71; 95% CI: 0.56, 0.90; P = 0.004). No significant correlation was found between phylloquinone and risk of all-cause mortality in those with BMI <25 kg/m².

Conclusions: In Chinese patients with hypertension, there was a significant negative association between baseline plasma phylloquinone and all-cause mortality, especially among those with higher BMI.

Keywords: BMI; all-cause mortality; nested case-control study; phylloquinone; vitamin K.