Plasma creatine concentration is associated with incident hypertension in a cohort enriched for the presence of high urinary albumin concentration: the Prevention of Renal and Vascular Endstage Disease study.

OBJECTIVE: : Hypertension is a major risk factor for cardiovascular disease, kidney disease, and premature death. Increased levels of creatine kinase are associated with development of hypertension. However, it is unknown if creatine, a substrate of CK, is associated with the development of hypertension. We therefore, aimed to investigate the association between plasma creatine concentration and incident hypertension. METHODS: We measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the population-based PREVEND study. The study outcome was incident hypertension, defined as either a SBP of at least 140 mmHg, a DBP of at least 90 mmHg, or the new usage of antihypertensive drugs. Participants with hypertension at baseline were excluded. RESULTS: We included 3135 participants (46% men) aged 49 ±â€Š10 years. Mean plasma creatine concentrations were 36.2 ±â€Š17.5 µmol/l, with higher concentrations in women than in men (42.2 ±â€Š17.6 versus 29.2 ±â€Š17.6 µmol/l; P < 0.001). During a median of 7.1 [interquartile range: 3.6-7.6] years of follow-up, 927 participants developed incident hypertension. Higher plasma creatine concentrations were associated with an increased risk of incident hypertension [HR per doubling of plasma creatine: 1.21 (95% confidence interval: 1.10-1.34); P < 0.001], which remained significant after adjustment for potential confounders. Sex-stratified analyses demonstrated higher plasma creatine that was independently associated with an increased risk of incident hypertension in men [hazard ratio: 1.26 (95% CI 1.11-1.44); P < 0.001], but not in women (hazard ratio: 1.13 (95% CI 0.96-1.33); P = 0.14]. Causal pathway analyses demonstrate that the association was not explained by sodium or protein intake. CONCLUSION: Higher plasma creatine is associated with an increased risk of hypertension in men. Future studies are warranted to determine the underlying mechanisms.

Circulating de novo lipogenesis fatty acids and all-cause mortality in a prospective Dutch population cohort.

BACKGROUND: Circulating fatty acids (FA) from de novo lipogenesis (DNL) are associated with all-cause mortality in individuals with elevated CVD risk. However, compared to FA early in the DNL synthetic pathway, cis-vaccenic acid, one of the FA distal in the DNL synthetic pathway, has rarely been studied in a general population cohort. We hypothesized that circulating cis-vaccenic acid is more strongly related to all-cause mortality than other circulating DNL-related FA. OBJECTIVES: The primary and secondary objectives of this study were to investigate the prospective associations of plasma levels of cis-vaccenic acid and other DNL-related FA with all-cause mortality in a general population, respectively. METHODS: We included 850 participants (mean ± SD age 53 ± 15 years) from the Dutch Lifelines cohort study. Circulating levels of palmitic (C16:0), palmitoleic (C16:1n7), cis-vaccenic (cis-C18:1n7), stearic (C18:0), oleic acid (C18:1n9) in plasma phospholipids (PL) and triglycerides (TG) were measured by gas chromatography. The associations of circulating cis-C18:1n7 and other DNL-related FA with all-cause mortality were assessed using Cox regression analyses. RESULTS: During a median follow-up of 9.3 (IQR: 5.4-10.8) years, 34 (4.0%) participants had died. In plasma PL, a 1-SD increase in cis-C18:1n7 was associated with an increased risk of all-cause mortality in univariate and multivariate models (p<0.02 for all), with a HR [95% CI] of 1.60 [1.13-2.25] after adjustment for age and sex. CONCLUSIONS: Circulating plasma PL cis-C18:1n7 was associated with a higher risk for all-cause mortality. More studies are needed in different cohorts to verify and validate our results.

Low Circulating Concentrations of Very Long Chain Saturated Fatty Acids Are Associated with High Risk of Mortality in Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of mortality, particularly from infectious diseases, due to lifelong immunosuppression. Although very long chain saturated fatty acids (VLSFA) have been identified as crucial for phagocytosis and clearance of infections, their association with mortality in immunocompromised patient groups has not been studied. In this prospective cohort study we included 680 outpatient KTR with a functional graft ≥1 year and 193 healthy controls. Plasma VLSFA (arachidonic acid (C20:0), behenic acid (C22:0) and lignoceric acid (C24:0)) were measured by gas chromatography coupled with a flame ionization detector. Cox regression analyses was used to prospectively study the associations of VLSFA with all-cause and cause-specific mortality. All studied VLSFA were significantly lower in KTR compared to healthy controls (all p < 0.001). During a median (interquartile range) follow-up of 5.6 (5.2-6.3) years, 146 (21%) KTR died, of which 41 (28%) died due to infectious diseases. In KTR, C22:0 was inversely associated with risk of all-cause mortality, with a HR (95% CI) per 1-SD-increment of 0.79 (0.64-0.99), independent of adjustment for potential confounders. All studied VLSFA were particularly strongly associated with mortality from infectious causes, with respective HRs for C20:0, C22:0 and C24:0 of 0.53 (0.35-0.82), 0.48 (0.30-0.75), and 0.51 (0.33-0.80), independent of potential confounders. VLSFA are inversely associated with infectious disease mortality in KTR after adjustment, including HDL-cholesterol. Further studies are needed to assess the effect of VLSFA-containing foods on the risk of infectious diseases in immunocompromised patient groups.