Introducing the importance and difficulties of a three-step approach to improve nonadherence to antihypertensive drugs: a case series.

Nonadherence to antihypertensive drugs is an important reason for not reaching blood pressure goals. A possible method to improve nonadherence involves three essential steps: identification of nonadherent patients (step 1), determination of underlying causes (step 2) and a personalized solution (step 3). We present three unique cases to show the importance and difficulties of this three-step approach. Patients participated in a randomized controlled trial to improve nonadherence to antihypertensive drugs (RHYME-RCT, Dutch Trial Register NL6736). Drug level measurements were used to identify nonadherence to antihypertensive drugs and communication on drug levels was supported by a tailored feedback tool in these patients. These cases showed that a three-step approach of identifying nonadherence and determination of the underlying cause, can lead to a personalized solution to improve therapy even when nonadherence was excluded. Open communication with patients remains an essential part when improving nonadherence.

Exploring food insecurity and obesity in Dutch disadvantaged neighborhoods: a cross-sectional mediation analysis.

BACKGROUND: Food insecurity is related to risk of adverse health outcomes such as obesity, but the explanatory factors underlying this association are still unclear. This study aimed to assess the association between food insecurity and obesity, and to explore potential mediation by sociodemographic and lifestyle factors. METHODS: This cross-sectional study was conducted among 250 participants in a deprived urban area in the Netherlands. Data on sociodemographic and lifestyle factors, food insecurity status and diet quality were collected using questionnaires. Diet quality was determined based on current national dietary guidelines. BMI was calculated from self-reported height and weight. Regression analyses were performed to explore the association between food insecurity and BMI status. Mediation analyses were performed to estimate the total-, direct-, and indirect effect and proportion of total effect mediated of the food insecurity-obesity association. RESULTS: The overall prevalence of food insecurity was 26%. Food insecurity was associated with obesity (OR = 2.49, 95%CI = 1.16, 5.33), but not with overweight (OR = 1.15, 95%CI = 0.54, 2.45) in the unadjusted model. The food insecurity-obesity association was partially mediated by living situation (proportion mediated: 15.4%), diet quality (- 18.6%), and smoking status (- 15.8%) after adjustment for other covariates. CONCLUSIONS: The findings of this study suggest an association between food insecurity and obesity. Living situation, diet quality and smoking status explained part, but not all, of the total association between food insecurity and obesity. Future longitudinal studies are warranted to examine the temporal order of the food insecurity-obesity association and potential mediators in this relationship. In addition, food insecurity and its potential consequences need to be taken into account in obesity prevention programs and policies.

Agreement between measurement of 25-hydroxyvitamin D3 in dried blood spot samples and serum in a Chinese population in the Netherlands.

Blood for determining 25-hydroxyvitamin D3 [25(OH)D3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this proof-of-concept study was to investigate levels of agreement between measurements of 25(OH)D3 obtained with DBS compared with serum. 301 Chinese participants were included who completed 25(OH)D3 measurement from DBS and from simultaneously collected blood samples obtained by venipuncture. Measurements of both DBS and serum 25(OH)D3 were performed using liquid chromatography followed by tandem mass spectrometry. Agreement between the two methods was assessed with Passing and Bablok regression analysis and Bland-Altman plot. Measurements showed a good correlation (Pearson's correlation coefficient r = 0.929, P < 0.001) between the two methods. After recalculating for a 13% difference, a regression equation of DBS 25(OH)D3 = -1.91 + 1.00 serum 25(OH)D3 was found in Passing and Bablok regression analysis. Bland-Altman analysis showed a fixed bias of 1.7 nmol/L; upper and lower limit of agreement was 24.1 nmol/L and -20.7 nmol/L, respectively. Sensitivity of recalculated DBS for 25(OH)D3 concentrations <30 and <50 nmol/L was 87.8% and 91.1%, respectively, and specificity was 89.2% and 83.1%, respectively. In conclusion, a good agreement was found between the measurement of 25(OH)D3 obtained with DBS compared with serum. DBS may possibly be used in a future screening program, but it is less suitable for individualized vitamin D status assessment.

Improvement of radiocephalic fistula maturation: rationale and design of the Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study - a randomized controlled trial.

BACKGROUND: Non-maturation is a frequent complication of radiocephalic arteriovenous fistulas (RCAVF). In an animal model, liposomal prednisolone improved maturation of experimental fistulas. The Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study investigates if liposomal prednisolone improves RCAVF maturation. METHODS AND RESULTS: The LIPMAT study is an investigator-initiated, multicenter, double-blinded, placebo-controlled randomized controlled trial with 1:1 randomization to liposomal prednisolone or placebo. Eighty patients receiving an RCAVF will be included. The primary outcome is the cephalic vein diameter six weeks after surgery, measured by ultrasound. The LIPMAT study started in May 2016. Enrollment is expected to be completed by the end of 2017. CONCLUSIONS: The LIPMAT study is the first to evaluate the efficacy of liposomal prednisolone to enhance RCAVF maturation.

Vitamin D status in the Chinese population in the Netherlands: The DRAGON study.

INTRODUCTION: Vitamin D is essential for bone health since it stimulates the intestinal absorption of calcium and phosphorus from the gut, both necessary for bone mineralization. However, vitamin D deficiency is highly prevalent among several non-Western immigrant populations in the Netherlands. To date, there are no data available of the vitamin D status in the Chinese population residing in the Netherlands. Therefore, an observational study was performed to determine 25-hydroxyvitamin D (25(OH)D) concentrations and to assess potential determinants of low vitamin D status. METHODS: Subjects, aged 18 years and older, with a Chinese background and residing in the Netherlands were invited to participate in the study. A questionnaire was used to assess general characteristics and lifestyle habits. Fasting blood samples were obtained in March 2014 to measure serum 25(OH)D concentration, and analysed by liquid chromatography tandem mass spectrometry. RESULTS: 418 subjects participated in the study, 104 men and 314 women. The mean age for both men and women was 56 years. Serum 25(OH)D concentration <50nmol/L was more prevalent in men than in women (67.9% and 53.1%, respectively; p=0.008). The percentage of serum 25(OH)D concentration<25nmol/L in men and women was 5.8% and 10.9%, respectively. Multiple logistic regression analysis, adjusted for age and gender, revealed that non-use of vitamin D supplements and fewer days per week of physical activity were significant predictors of serum 25(OH)D levels below 50nmol/L. CONCLUSIONS: Within the Chinese population living in the Netherlands, serum 25(OH)D concentration was below 50nmol/L in 68% of men and 53% of women. Use of vitamin D supplements by Chinese people in the Netherlands was highly protective against low 25(OH)D levels.

Effect on blood pressure of combined inhibition of endothelin-converting enzyme and neutral endopeptidase with daglutril in patients with type 2 diabetes who have albuminuria: a randomised, crossover, double-blind, placebo-controlled trial.

BACKGROUND: Effective reduction of albuminuria and blood pressure in patients with type 2 diabetes who have nephropathy is seldom achieved with available treatments. We tested the effects of treatment of such patients with daglutril, a combined endothelin-converting enzyme and neutral endopeptidase inhibitor. METHODS: We did this randomised, crossover trial in two hospitals in Italy. Eligibility criteria were: age 18 years or older, urinary albumin excretion 20-999 µg/min, systolic blood pressure (BP) less than 140 mm Hg, and diastolic BP less than 90 mm Hg. Patients were randomly assigned (1:1) with a computer-generated randomised sequence to receive either daglutril (300 mg/day) then placebo for 8 weeks each or vice versa, with a 4-week washout period. Patients also took losartan throughout. Participants and investigators were masked to treatment allocation. The primary endpoint was 24-h urinary albumin excretion in the intention-to-treat population. Secondary endpoints were median office and ambulatory (24 h, daytime, and night-time) BP, renal haemodynamics and sieving function, and metabolic and laboratory test results. This study is registered with ClinicalTrials.gov, number NCT00160225. FINDINGS: We screened 58 patients, of whom 45 were enrolled (22 assigned to daglutril then placebo, 23 to placebo then daglutril; enrolment from May, 2005, to December, 2006) and 42 (20 vs 22) were included in the primary analysis. Daglutril did not significantly affect 24-h urinary albumin excretion compared with placebo (difference in change -7·6 µg/min, IQR -78·7 to 19·0; p=0·559). 34 patients had complete 24-h BP readings; compared with placebo, daglutril significantly reduced 24-h systolic (difference -5·2 mm Hg, SD 9·4; p=0·0013), diastolic (-2·5, 6·2; p=0·015), pulse (-3·0, 6·3; p=0·019), and mean (-3·1, 6·2; p=0·003) BP, as well as all night-time BP readings and daytime systolic, pulse, and mean BP, but not diastolic BP. Compared with placebo, daglutril also significantly reduced office systolic BP (-5·4, 15·4; p=0·028), but not diastolic (-1·8, 9·9; p=0·245), pulse (-3·1, 10·6; p=0·210), or mean (-2·1, 10·4; p=0·205) BP, and increased big endothelin serum concentration. Other secondary outcomes did not differ significantly between treatment periods. Three patients taking placebo and six patients taking daglutril had mild treatment-related adverse events--the most common was facial or peripheral oedema (in four patients taking daglutril). INTERPRETATION: Daglutril improved control of BP in hypertensive patients with type 2 diabetes and nephropathy and had an acceptable safety profile. Combined endothelin-converting enzyme and neutral endopeptidase inhibition could provide a new approach to hypertension in this high-risk population. FUNDING: Solvay Pharmaceuticals.

The diabetic CKD patient--a major cardiovascular challenge.

The diabetic patient with chronic kidney disease (CKD) is at very high risk of cardiovascular disease (CVD). Primary and secondary CVD prevention is of major importance and should be targeted at both traditional cardiovascular risk factors and risk factors specific for patients with CKD, such as albuminuria, anaemia and CKD--mineral and bone disorder. However, treatment goals have largely been derived from clinical trials including patients with no or only mild CKD and may not be generalizable to patients with advanced renal disease. Moreover, in patients on renal replacement therapy, the association between traditional CVD risk factors and the incidence of CVD may be reversed, and pharmaceutical interventions that are beneficial in the general population may be ineffective or even harmful in this high-risk population. Those involved in the delivery of care to patients with diabetes and CKD need to be aware of these issues and should adopt an individualised approach to treatment.

The role of renin angiotensin system inhibition in kidney repair.

Chronic kidney diseases share common pathogenic mechanisms that, independently from the initial injury, lead to glomerular hyperfiltration, proteinuria, and progressive renal scarring and function loss. Inhibition of the renin angiotensin system (RAS) has been consistently found to reduce or halt the progressive deterioration of renal function through reduction of blood pressure and proteinuria, the two main determinants of renal function decline. In few instances, RAS inhibition may even promote amelioration of the glomerular filtration rate. Animal data suggest that chronic therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor type I blockers promotes regression of glomerulosclerosis, even in later phases of the disease. In humans, studies investigating the effect of angiotensin II inhibition on renal structural changes have shown inconsistent results, possibly due to small numbers and/or short duration of follow-up. Whether regression of glomerulosclerosis relies on a direct regenerative effect of RAS inhibition or on spontaneous kidney self-repair after the injury has been removed is still unknown. Improved understanding of mechanisms that promote renal regeneration may help in designing specific therapies to prevent the development of end-stage renal disease. This is a desirable goal, considering the economic burden of chronic kidney diseases and their effect on morbidity and mortality.

Successes and disappointments with clinical islet transplantation.

Transplantation of pancreatic islets is considered a therapeutic option for patients with type 1 diabetes mellitus who have life-threatening hypoglycaemic episodes. After the procedure, a decrease in the frequency and severity of hypoglycaemic episodes and sustained graft function as indicated by detectable levels of C-peptide can be seen in the majority of patients. However, true insulin independence, if achieved, usually lasts for at most a few years. Apart from the low insulin independence rates, reasons for concern regarding this procedure are the side effects of the immunosuppressive therapy, allo-immunization, and the high costs. Moreover, whether islet transplantation prevents the progression of diabetic micro- and macrovascular complications is largely unknown. Areas of current research include the development of less toxic immunosuppressive regimens, the control of the inflammatory reaction immediately after transplantation, the identification of the optimal anatomical site for islet infusion, and the possibility to encapsulate transplanted islets to protect them from the allo-immune response. At present, pancreatic islet transplantation is still an experimental procedure, which is only indicated for a highly selected group of type 1 diabetic patients with life-threatening hypoglycaemic episodes.

Fatty fish and supplements are the greatest modifiable contributors to the serum 25-hydroxyvitamin D concentration in a multiethnic population.

OBJECTIVE: Because vitamin D synthesis is lower in a heavily pigmented skin than in a lighter skin, the relative contribution of determinants to the vitamin D concentration might differ between ethnic groups. The aim of this study was to assess the prevalence of vitamin D deficiency and the relative contribution of vitamin D consumption and exposure to sunlight to the vitamin D concentration in a multiethnic population. DESIGN: Cross-sectional study. PATIENTS: A total of 613 adults aged 18-65 years from a random sample from general practices in the Netherlands (52 degrees N, 2003-05), stratified according to gender and ethnic group. MEASUREMENTS: Serum 25-hydroxyvitamin D [25(OH)D], PTH, ethnic group, sunlight exposure, consumption of foods and supplements rich in vitamin D. RESULTS: The prevalence (95% confidence interval) of vitamin D deficiency [serum 25(OH)D < 25 nmol/l] was higher in Turkish (41.3%; 32.5-50.1), Moroccan (36.5%; 26.9-46.1), Surinam South Asian (51.4%; 41.9-60.9), Surinam Creole (45.3%; 34.0-56.6), sub-Saharan African (19.3%; 9.1-29.5) and other adults (29.1%; 17.1-41.1) compared to the indigenous Dutch (5.9%; 1.3-10.5). Modifiable, significant determinants (standardized regression coefficients) for serum 25(OH)D concentration were: consumption of fatty fish (0.160), use of vitamin D supplements (0.142), area of uncovered skin (highest category 0.136; middle category 0.028), use of tanning bed (0.103), consumption of margarine (0.093) and preference for sun (0.089). We found no significant modification of ethnic group on the effect of sunlight determinants. CONCLUSION: Of the modifiable determinants, fatty fish and supplements are the greatest contributors to the serum 25(OH)D concentration in a multiethnic population.

High prevalence of vitamin D deficiency in pregnant non-Western women in The Hague, Netherlands.

BACKGROUND: Vitamin D deficiency is common in dark-skinned persons living in northern countries. Vitamin D deficiency during pregnancy may have serious consequences for both mother and child. OBJECTIVE: The objective was to ascertain the prevalence of vitamin D deficiency in pregnant women of several ethnic backgrounds who were living in The Hague, a large city in the Netherlands. DESIGN: Midwives whose practice was visited by a large number of non-Western immigrants added the assessment of serum 25-hydroxyvitamin D [25(OH)D] to the standard blood test given to women who visited the practice during week 12 of pregnancy. Subsequently, the Municipal Health Service collected additional data from the midwives' files (June 2002 through March 2004): background variables, use of tobacco or alcohol or drugs, and infectious diseases. The women were grouped ethnically as Western, Turkish, Moroccan, and other non-Western. RESULTS: The vitamin D concentrations of 358 women were found in the midwives' files. Of these women, 29% were Western, 22% were Turkish, and 19% were Moroccan. Mean serum 25(OH)D concentrations in Turkish (15.2 +/- 12.1 nmol/L), Moroccan (20.1 +/- 13.5 nmol/L), and other non-Western women (26.3 +/- 25.9 nmol/L) were significantly (P

Soluble Fas, a mediator of apoptosis, C-reactive protein, and coronary and extracoronary atherosclerosis. The Rotterdam Coronary Calcification Study.

RATIONALE: Findings from laboratory studies strongly suggest a role for apoptosis, the process of programmed cell death, in cardiovascular disease. No population-based study has yet investigated whether serum levels of soluble forms of Fas, a receptor capable of inducing the apoptosis cascade, are associated with coronary and extracoronary atherosclerosis. METHODS: Within the Rotterdam Coronary Calcification Study, a population-based cohort study, we measured coronary calcification using electron-beam computed tomography, abdominal aortic calcification by abdominal X-ray, carotid plaques and common carotid intima-media thickness (IMT) by ultrasonography, and lower extremity atherosclerosis by computation of the ankle-arm index. Levels of sFas and of the inflammatory mediator C-reactive protein (CRP) were measured in 1036 participants. RESULTS: Levels of sFas were not related to coronary or extracoronary atherosclerosis. CRP showed strong associations with measures of atherosclerosis, including coronary atherosclerosis, which largely remained after adjustment for traditional cardiovascular risk factors. CONCLUSION: The results of this study do not support a role for sFas in the identification of subjects with atherosclerosis.

Lipoprotein-associated phospholipase A2 and measures of extracoronary atherosclerosis: the Rotterdam Study.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) may be a new and independent predictor of cardiovascular events. The effect of Lp-PLA2 may be exerted through effects of the enzyme on the development of atherosclerosis. Therefore, we investigated the association between Lp-PLA2 activity and measures of extracoronary atherosclerosis. METHODS AND RESULTS: Lp-PLA2 activity was determined in a random sample of 1820 participants from the Rotterdam Study, a population-based cohort study in men and women > or =55 years. Common carotid intima-media thickness, carotid plaques, ankle-arm index, and aortic calcification were examined. Atherosclerosis status could be assigned in 1609 participants. The age-adjusted odds ratio of having atherosclerosis at any site for the highest versus the lowest tertile of Lp-PLA2 activity was 1.86 (95% CI, 1.01 to 3.43) in men and 1.60 (95% CI, 1.08 to 2.37) in women. After additional adjustment for cholesterol, these associations attenuated or even disappeared. The odds ratios of having atherosclerosis at specific sites (carotid arteries and aortic-iliac-femoral tract) followed a similar pattern. CONCLUSIONS: Although Lp-PLA2 has been found to be independently associated with cardiovascular events, the association with measures of subclinical extracoronary atherosclerosis found in this study strongly attenuated or even disappeared after adjustment for cholesterol.

Lipoprotein-associated phospholipase A2 is associated with risk of dementia.

OBJECTIVE: High levels of the inflammatory marker lipoprotein-associated phospholipase A2 (Lp-PLA2) have been proposed to be a predictor of coronary heart disease and stroke. Because both inflammation and vascular disease are associated with dementia, the objective of the present study was to examine the association between Lp-PLA2 and the risk of dementia. METHODS: Within the Rotterdam Study, a population-based prospective cohort study, we performed a case-cohort study. Of the 6,713 participants at risk for dementia, a random sample of 1,742 individuals was drawn. During follow-up (mean, 5.7 years), 302 incident dementia cases were identified. Cox proportional hazard models were used to estimate the association of Lp-PLA2 and dementia. RESULTS: We found that subjects with higher levels of Lp-PLA2 had an increased risk of dementia. Compared with the first quartile of Lp-PLA2, age- and sex-adjusted hazard ratios (HRs; 95% confidence interval [CI]) for dementia for the second, third, and fourth quartiles were 1.19 (0.78-1.81), 1.15 (0.74-1.79), and 1.56 (1.03-2.37), respectively (p value for trend 0.04). Additional adjustment for cardiovascular and inflammatory factors did not change the estimates. INTERPRETATION: This is the first study to our knowledge that shows that Lp-PLA2 is associated with the risk of dementia independent of cardiovascular and inflammatory factors and provides evidence for a potential role of Lp-PLA2 in identifying subjects at risk for dementia.

Evaluation of plasma lactate as a parameter for disease severity on admission in travelers with Plasmodium falciparum malaria.

BACKGROUND: Rapid immunochromatographic dipstick assays are used increasingly in many tropical and Western countries as a tool to diagnose Plasmodium falciparum malaria. However, these tests do not provide any information about the severity of the infection. We evaluated the usefulness of plasma lactate as a parameter for disease severity on admission in imported P. falciparum malaria. METHODS: In a cohort of 61 nonimmune travelers with imported P. falciparum malaria, plasma lactate levels on admission were related to the severity of the infection. Results from 12 of 61 patients fulfilled the criteria of severe malaria. RESULTS: Logistic regression analysis showed that a plasma lactate level above the upper range of normal was associated with an odds ratio of 31 (95% CI 6-164) for severe malaria. As a continuous variable, a 1 mmol/L increase in plasma lactate level was associated with an odds ratio of 12 (95% CI 3-50) for severe malaria. The sensitivity of an increased plasma lactate level on admission for severe malaria was 67% with a specificity of 94%. CONCLUSIONS: A timely determination of plasma lactate on admission may be helpful in the assessment of disease severity in travelers with imported P. falciparum malaria. An increased plasma lactate level should raise suspicion of a severe P. falciparum malaria infection, in particular when concomitant infections are not considered likely.

Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory marker of cardiovascular disease. In the present study, we investigated whether Lp-PLA2 is an independent predictor of coronary heart disease and ischemic stroke. METHODS AND RESULTS: The Rotterdam Study is a population-based follow-up study in 7983 subjects > or =55 years of age. We performed a case-cohort study, including 308 coronary heart disease cases, 110 ischemic stroke cases, and a random sample of 1820 subjects. We used Cox proportional-hazard models with modification of the standard errors based on robust variance estimates to compute hazard ratios adjusted for age, sex, body mass index, systolic blood pressure, non-HDL cholesterol, HDL cholesterol, diabetes, smoking, alcohol consumption, cholesterol-lowering medication, white blood cell count, and C-reactive protein. Compared with the first quartile of Lp-PLA2 activity, multivariate-adjusted hazard ratios for coronary heart disease for the second, third, and fourth quartiles were 1.39 (95% CI, 0.92 to 2.10), 1.99 (95% CI, 1.32 to 3.00), and 1.97 (95% CI, 1.28 to 3.02), respectively (P for trend=0.01). Corresponding multivariate-adjusted hazard ratios for ischemic stroke were 1.08 (95% CI, 0.55 to 2.11), 1.58 (95% CI, 0.82 to 3.04), and 1.97 (95% CI, 1.03 to 3.79) (P for trend=0.03). The relation between Lp-PLA2 and coronary heart disease was present in both subjects with non-HDL cholesterol levels below the median and those with non-HDL cholesterol levels above the median. CONCLUSIONS: This study shows that Lp-PLA2 activity is an independent predictor of coronary heart disease and ischemic stroke in the general population.

Genetic variation in Fcgamma receptor IIa protects against advanced peripheral atherosclerosis. The Rotterdam Study.

Immune processes play a substantial role in atherosclerotic disease. The role in atherosclerosis of Fcgamma receptor IIa (FcgammaRIIa), a receptor for immunoglobulin G and for the inflammatory mediator C-reactive protein, is not yet clear. Since the R/H131 polymorphism in the FcgammaRIIa gene strongly influences binding to FcgammaRIIa, we investigated the association of the R/H131 polymorphism with advanced peripheral atherosclerosis. Within the Rotterdam Study, a population-based cohort study, we determined FcgammaRIIa genotype in 430 subjects with advanced peripheral atherosclerosis as indicated by the ankle-arm index, and 411 controls. Heterozygous and homozygous carriers of the H131 allele were protected against advanced peripheral atherosclerosis (age- and gender-adjusted odds ratio (OR) 0.77 (0.54-1.12) and 0.65 (0.44-0.98), respectively, P trend=0.04). This effect was most pronounced in subjects with modestly elevated levels of inflammation as indicated by the leukocyte count (OR 0.52 (0.29-0.93) and 0.45 (0.23-0.86), for heterozygotes and H131 homozygotes, respectively; P trend=0.02). This is the first study showing that the H131 allele of FcgammaRIIa protects against advanced peripheral atherosclerosis.

Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study.

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.