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Associations of coronary artery calcified plaque density with mortality in type 2 diabetes: the Diabetes Heart Study.

ABSTRACT: BACKGROUND:Coronary artery calcified plaque (CAC) is strongly predictive of cardiovascular disease (CVD) events and mortality, both in general populations and individuals with type 2 diabetes at high risk for CVD. CAC is typically reported as an Agatston score, which is weighted for increased plaque density. However, the role of CAC density in CVD risk prediction, independently and with CAC volume, remains unclear. METHODS:We examined the role of CAC density in individuals with type 2 diabetes from the family-based Diabetes Heart Study and the African American-Diabetes Heart Study. CAC density was calculated as mass divided by volume, and associations with incident all-cause and CVD mortality [median follow-up 10.2 years European Americans (n?=?902, n?=?286 deceased), 5.2 years African Americans (n?=?552, n?=?93 deceased)] were examined using Cox proportional hazards models, independently and in models adjusted for CAC volume. RESULTS:In European Americans, CAC density, like Agatston score and volume, was consistently associated with increased risk of all-cause and CVD mortality (p???0.002) in models adjusted for age, sex, statin use, total cholesterol, HDL, systolic blood pressure, high blood pressure medication use, and current smoking. However, these associations were no longer significant when models were additionally adjusted for CAC volume. CAC density was not significantly associated with mortality, either alone or adjusted for CAC volume, in African Americans. CONCLUSIONS:CAC density is not associated with mortality independent from CAC volume in European Americans and African Americans with type 2 diabetes.

SUBMITTER: Raffield LM

PROVIDER: S-EPMC5946410 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Associations of coronary artery calcified plaque density with mortality in type 2 diabetes: the Diabetes Heart Study.

Raffield Laura M LM Cox Amanda J AJ Criqui Michael H MH Hsu Fang-Chi FC Terry James G JG Xu Jianzhao J Freedman Barry I BI Carr J Jeffrey JJ Bowden Donald W DW

Cardiovascular diabetology 20180511 1

<h4>Background</h4>Coronary artery calcified plaque (CAC) is strongly predictive of cardiovascular disease (CVD) events and mortality, both in general populations and individuals with type 2 diabetes at high risk for CVD. CAC is typically reported as an Agatston score, which is weighted for increased plaque density. However, the role of CAC density in CVD risk prediction, independently and with CAC volume, remains unclear.<h4>Methods</h4>We examined the role of CAC density in individuals with ty ...[more]

PMID: 29751802

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Project description:ImportancePlaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known.ObjectiveTo ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS.Design, setting, and participantsThis multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019.ExposuresWhole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque).Main outcomes and measuresAssociation between calcium density and future ACS risk.ResultsA total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases.Conclusions and relevanceResults of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

Project description:BackgroundPrevious studies primarily targeted the ability of polygenic risk scores (PRSs) to predict a specific disease, and only a few studies have investigated the association between genetic risk scores and cardiovascular (CV) mortality. We assessed PRSs for coronary artery disease (CAD) and type 2 diabetes (T2DM) as the predictive factors for CV mortality, independent of traditional risk factors, and further investigated the additive effect between lifestyle behavior and PRS on CV mortality.MethodsWe used genetic and phenotypic data from UK Biobank participants aged 40-69 years at baseline, collected with standardized procedures. Genome-wide PRSs were constructed using >6 million genetic variants. Cox proportional hazard models were used to analyze the relationship between PRS and CV mortality with stratification by age, sex, disease status, and lifestyle behavior.ResultsOf 377,909 UK Biobank participants having European ancestry, 3,210 (0.8%) died due to CV disease during a median follow-up of 8.9 years. CV mortality risk was significantly associated with CAD PRS [low vs. very high genetic risk groups, CAD PRS hazard ratio (HR) 2.61 (2.02-3.36)] and T2DM PRS [HR 2.08 (1.58-2.73)], respectively. These relationships remained significant even after an adjustment for a comprehensive range of demographic and clinical factors. In the very high genetic risk group, adherence to an unfavorable lifestyle was further associated with a substantially increased risk of CV mortality [favorable vs. unfavorable lifestyle with very high genetic risk for CAD PRS, HR 8.31 (5.12-13.49); T2DM PRS, HR 5.84 (3.39-10.04)]. Across all genetic risk groups, 32.1% of CV mortality was attributable to lifestyle behavior [population attributable fraction (PAF) 32.1% (95% CI 28.8-35.3%)] and 14.1% was attributable to smoking [PAF 14.1% (95% CI 12.4-15.7%)]. There was no evidence of significant interaction between PRSs and age, sex, or lifestyle behavior in predicting the risk of CV mortality.ConclusionPRSs for CAD or T2DM and lifestyle behaviors are the independent predictive factors for future CV mortality in the white, middle-aged population. PRS-based risk assessment could be useful to identify the individuals who need intensive behavioral or therapeutic interventions to reduce the risk of CV mortality.

Dataset Information

Associations of coronary artery calcified plaque density with mortality in type 2 diabetes: the Diabetes Heart Study.

Publications

Associations of coronary artery calcified plaque density with mortality in type 2 diabetes: the Diabetes Heart Study.

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