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Vitamin K-Dependent Protein Activity and Incident Ischemic Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

ABSTRACT: OBJECTIVE:Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular disease has not been studied. APPROACH AND RESULTS:VKDP activity was determined by measuring circulating des-?-carboxy prothrombin concentrations in a random sample of 709 multiethnic adults free of cardiovascular disease drawn from the Multi-Ethnic Study of Atherosclerosis (MESA). Lower des-?-carboxy prothrombin concentrations reflect greater VKDP activity. Subjects were followed up for the risk of ischemic cardiovascular disease (coronary heart disease, stroke, and fatal cardiovascular disease) for 11.0 years of follow-up. A total of 75 first ischemic CVD events occurred during follow-up. The incidence of ischemic cardiovascular disease increased progressively across des-?-carboxy prothrombin quartiles, with event rates of 5.9 and 11.7 per 1000 person-years in the lowest and highest quartiles. In analyses adjusted for traditional cardiovascular risk factors and measures of vitamin K intake, a doubling of des-?-carboxy prothrombin concentration was associated with a 1.53 (95% confidence interval, 1.09-2.13; P=0.008) higher risk of incident ischemic cardiovascular disease. The association was consistent across strata of participants with diabetes mellitus, hypertension, renal impairment, and low vitamin K nutritional intake. CONCLUSIONS:In this sample of middle-aged and older adults, VKDP activity was associated with incident ischemic cardiovascular events. Further studies to understand the role of this large class of proteins in cardiovascular disease are warranted.

SUBMITTER: Danziger J

PROVIDER: S-EPMC5844474 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Vitamin K-Dependent Protein Activity and Incident Ischemic Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

Danziger John J Young Rebekah L RL Shea M Kyla MK Tracy Russell P RP Ix Joachim H JH Jenny Nancy S NS Mukamal Kenneth J KJ

Arteriosclerosis, thrombosis, and vascular biology 20160331 5

<h4>Objective</h4>Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular disease has not been studied.<h4>Approach and results</h4>VKDP activity was determined by measuring circulating des-γ-carboxy prothrombin concentrations in a random sample of 709 multiethnic adults f ...[more]

PMID: 27034472

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Project description:BackgroundThe 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up.MethodsWe included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes.ResultsWe studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32-3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01-2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06-2.33).ConclusionsCurrent cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Project description:BACKGROUND:Worldwide clinical practice guidelines for dyslipidemia emphasize allocating statin therapy to those at the highest absolute atherosclerotic cardiovascular disease (CVD) risk. METHODS AND RESULTS:We examined 5534 Multi-Ethnic Study of Atherosclerosis (MESA) participants who were not on baseline medications for dyslipidemia. Participants were classified by baseline coronary artery calcium (CAC) score (>0, ? 100) and the common clinical scheme of counting lipid abnormalities (LA), including low-density lipoprotein cholesterol ? 3.36 mmol/L (130 mg/dL), high-density lipoprotein cholesterol <1.03 mmol/L (40 mg/dL) for men or <1.29 mmol/L (50 mg/dL) for women, and triglycerides ? 1.69 mmol/L (150 mg/dL). Our main outcome measure was incident CVD (myocardial infarction, angina resulting in revascularization, resuscitated cardiac arrest, stroke, cardiovascular death). Over a median follow-up of 7.6 years, more than half of events (55%) occurred in the 21% of participants with CAC ? 100. Conversely, 65% of events occurred in participants with 0 or 1 LA. In those with CAC ? 100, CVD rates ranged from 22.7 to 29.5 per 1000 person-years across LA categories. In contrast, with CAC=0, CVD rates ranged from 2.7 to 5.9 per 1000 person-years across LA categories. Individuals with 0 LA and CAC ? 100 had a higher event rate compared with individuals with 3 LA but CAC=0 (22.7 versus 5.9 per 1000 person-years). Similar results were obtained when we classified LA using data set quartiles of total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or low-density lipoprotein particle concentration and guideline categories of low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. CONCLUSIONS:CAC may have the potential to help match statin therapy to absolute CVD risk. Across the spectrum of dyslipidemia, event rates similar to secondary prevention populations were observed for patients with CAC ? 100.

Dataset Information

Vitamin K-Dependent Protein Activity and Incident Ischemic Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

Publications

Vitamin K-Dependent Protein Activity and Incident Ischemic Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

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