Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis

Objectives: Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins (VKDP) are associated with VS and VC and require vitamin K for activity. We conducted a systematic review and meta-analysis of: (1) the effect of vitamin K supplementation on VS and VC and (2) association of inactive VKDP levels with incident cardiovascular disease and mortality. Methods: Two authors searched MEDLINE and Embase databases and Cochrane and ISRCTN registries for studies of vitamin K clinical trials that measured effects on VC, VS or VKDP and longitudinal studies assessing effect of VKDP on incident CVD or mortality. Random effects meta-analyses were performed. Results: Thirteen controlled clinical trials (n=2162) and 14 longitudinal studies (n=10 726) met prespecified inclusion criteria. Vitamin K supplementation was associated with significant reduction in VC (−9.1% (95% CI −17.7 to −0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; −44.7% (95% CI −65.1 to −24.3), p<0.0001) and uncarboxylated osteocalcin; −12.0% (95% CI −16.7 to −7.2), p<0.0001) compared with control, with a non-significant improvement in VS. In longitudinal studies with median follow-up of 7.8 (IQR 4.9–11.3) years, VKDP levels were associated with a combined endpoint of CVD or mortality (HR 0.45 (95% CI 0.07 to 0.83), p=0.02). Conclusions: Supplementation with vitamin K significantly reduced VC, but not VS, compared with control. The conclusions drawn are limited by small numbers of studies with substantial heterogeneity. VKDP was associated with combined endpoint of CVD or mortality. Larger clinical trials of effect of vitamin K supplementation to improve VC, VS and long-term cardiovascular health are warranted. Trial registration number: CRD42017060344

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87–0.94), with an additional relative risk for CVD of 0.92 (0.87–0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75–0.93), 0.76 (0.67–0.85), 0.69 (0.59–0.79), or 0.63 (0.52–0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials

Association between bisphosphonate therapy and rehabilitation outcomes in older people

No abstract available

Vitamin D Therapy to Reduce Blood Pressure and Left Ventricular Hypertrophy in Resistant Hypertension Randomized, Controlled Trial Original Article

R esistant hypertension, defined as an office systolic blood pressure of >140 mm Hg or diastolic blood pressure of >90 mm Hg, despite maximally tolerated treatment with ≥3 antihypertensive agents, affects 10% to 30% of patients with hypertension. 1 Resistance to treatment is associated with a high incidence of cardiovascular events. 2 Resistant hypertension is also associated with a high incidence of left ventricular (LV) hypertrophy, 3 itself a risk factor for cardiovascular events, arrhythmias, and death. Low vitamin D levels are associated with higher blood pressure 7 and a higher rate of both incident hypertension 8 and cardiovascular disease 9,10 in observational studies. Previous intervention trials 14,15 Therefore, we conducted a randomized controlled trial to test the effect of intermittent high-dose vitamin D on 24-hour ambulatory blood pressure and LV mass in patients with resistant hypertension. Abstract-Low 25-hydroxyvitamin D levels are associated with higher prevalent blood pressure. We tested whether high-dose intermittent oral vitamin D therapy could reduce blood pressure and left ventricular mass in patients with hypertension resistant to conventional treatment. We conducted a parallel-group, double-blind, randomized placebo-controlled trial. Patients with supine office blood pressure >140/90 mm Hg on ≥3 antihypertensive agents received 100 000 U oral vitamin D3 or matching placebo every 2 months. Office and 24-hour ambulatory blood pressure, glucose, and cholesterol were measured at baseline, 2, 4, and 6 months; left ventricular mass index was measured by cardiac MRI on a subgroup at baseline and 6 months. The primary outcome was mean 24-hour ambulatory blood pressure at 6 months. A total of 68 participants were randomized, 34 in each group. Mean age was 63 (SD 11) years, mean baseline office blood pressure was 154/84 (13/10) mm Hg, and mean baseline 25-hydroxyvitamin D level was 4