Dataset Information

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:AimWe assess the improvement in discrimination afforded by the addition of the computed tomography risk markers thoracic aorta calcium (TAC), aortic valve calcification (AVC), mitral annular calcification (MAC), pericardial adipose tissue volume (PAT), and liver attenuation (LA) to the Framingham risk score (FRS) + coronary artery calcium (CAC) for incident coronary heart disease (CHD) and incident cerebrovascular disease (CVD) in a multiethnic cohort.Methods and resultsA total of 5745 participants were enrolled, with 2710 at intermediate Framingham risk, 210 CVD events, and 155 CHD events). Over 9 years of follow up, 251 had adjudicated CHD, 346 had CVD events, and 321 died. The data were analysed using Cox proportional hazard, receiver operator curve (ROC), and net reclassification improvement (NRI) analyses. In the whole cohort and also when the analysis was restricted to only the intermediate-risk participants, CAC, TAC, AVC, and MAC were all significantly associated with incident CVD, incident CHD, and mortality, and CAC had the strongest association. When added to the FRS, CAC had the highest area under the curve (AUC) for the prediction of incident CVD and incident CHD; LA had the least. The addition of TAC, AVC, MAC, PAT, and LA to FRS + CAC all resulted in a significant reduction in AUC for incident CHD (0.712 vs. 0.646, 0.655, 0.652, 0.648, and 0.569; all p < 0.01, respectively) in participants with intermediate FRS. The addition of CAC to FRS resulted in an NRI of 0.547 for incident CHD in the intermediate-risk group. The NRI when TAC, AVC, MAC, PAT, and LA were added to FRS + CAC were 0.024, 0.026, 0.019, 0.012, and 0.012, respectively, for incident CHD in the intermediate-risk group. Similar results were obtained for incident CVD in the intermediate-risk group and also when the whole cohort was used instead of the intermediate FRS group.ConclusionsThe addition of CAC to the FRS provides superior discrimination especially in intermediate-risk individuals compared with the addition of TAC, AVC, MAC, PAT, or LA for incident CVD and incident CHD. Compared with FRS + CAC, the addition of TAC, AVC, MAC, PAT, or LA individually to FRS + CAC worsens the discrimination for incident CVD and incident CHD. These risk markers are unlikely to be useful for improving cardiovascular risk prediction.

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.

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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