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The Association of Coronary Artery Calcification With Subsequent Incidence of Cardiovascular Disease in Type 1 Diabetes: The DCCT/EDIC Trials.

ABSTRACT: OBJECTIVES:This study sought to determine the relationship between coronary artery calcium (CAC) scores and subsequent cardiovascular disease (CVD) events in DCCT (Diabetes Control and Complications Trial)/EDIC (Epidemiology of Diabetes Interventions and Complications) participants. BACKGROUND:The CAC score has been validated for improved risk stratification in general populations; however, this association has not been well studied in type 1 diabetes (T1DM). METHODS:Computed tomography (CT) to measure CAC was performed in 1,205 DCCT/EDIC participants at a mean of 42.8 years of age during EDIC years 7 to 9, after the end of DCCT. This study analyzed the association between CAC and time to the first subsequent CVD event or to the first major adverse cardiac event (MACE), a follow-up of 10 to 13 years. CAC was categorized as: 0, >0 to 100, >100 to 300, or >300 Agatston units. RESULTS:Of 1,156 participants at risk for subsequent CVD, 105 had an initial CVD event (8.5 per 1,000 patient-years); and of 1,187 participants at risk for MACE, 51 had an initial MACE event (3.9 per 1,000 patient-years). Event rates among those with scores of zero (n = 817 [70.7%]) were very low for CVD (5.6 per 1,000 patient years). CAC scores >100 to 300 (hazard ratio [HR]: 4.17, 5.40) and >300 (HR: 6.06, 6.91) were associated with higher risks of CVD and MACE, respectively, compared to CAC of 0 (p < 0.0001). CAC scores >0 to 100 were nominally associated with CVD (HR: 1.71; p = 0.0415) but not with MACE (HR: 1.11; p = 0.8134). Similar results were observed when also adjusted for mean HbA1c and conventional CVD risk factors. The increment in the AUC due to CAC was modest. CONCLUSIONS:CAC scores >100 Agatston units were significantly associated with an increased risk of the subsequent occurrence of CVD and MACE in DCCT/EDIC cohort. (Diabetes Control and Complications Trial [DCCT]; NCT00360815; Epidemiology of Diabetes Interventions and Complications [EDIC]; NCT00360893).

SUBMITTER: Budoff M

PROVIDER: S-EPMC6612565 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The Association of Coronary Artery Calcification With Subsequent Incidence of Cardiovascular Disease in Type 1 Diabetes: The DCCT/EDIC Trials.

Budoff Matthew M Backlund Jye-Yu C JC Bluemke David A DA Polak Joseph J Bebu Ionut I Schade David D Strowig Suzanne S Raskin Philip P Lachin John M JM

JACC. Cardiovascular imaging 20190313 7 Pt 2

<h4>Objectives</h4>This study sought to determine the relationship between coronary artery calcium (CAC) scores and subsequent cardiovascular disease (CVD) events in DCCT (Diabetes Control and Complications Trial)/EDIC (Epidemiology of Diabetes Interventions and Complications) participants.<h4>Background</h4>The CAC score has been validated for improved risk stratification in general populations; however, this association has not been well studied in type 1 diabetes (T1DM).<h4>Methods</h4>Comput ...[more]

PMID: 30878435

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Project description:BackgroundHyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus.Methods and ResultsA random subcohort of 349 participants was selected from the DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT, and 1 to 2 years post‐DCCT (EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F isoprostanes, and its metabolite, 2,3 dinor‐8 prostaglandin F. Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 prostaglandin F, an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, <0.003; −5.3% risk for 10% higher 2,3 dinor‐8 prostaglandin F, =0.0092). In contrast, the oxidative markers myeloperoxidase and F isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments.ConclusionsHeightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00360815 and NCT00360893.

Project description:Background and objectivesIn trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes.Design, setting, participants, & measurementsWe studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30-299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m2 on two consecutive visits), and subclinical cardiovascular disease.ResultsAt least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification.ConclusionsIn type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.

Project description:The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cholesterol management defined new eligibility criteria for statin therapy. However, it is unclear whether this approach improves identification of adults at higher risk of cardiovascular events.To determine whether the ACC/AHA guidelines improve identification of individuals who develop incident cardiovascular disease (CVD) and/or have coronary artery calcification (CAC) compared with the National Cholesterol Education Program's 2004 Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines.Longitudinal community-based cohort study, with participants for this investigation drawn from the offspring and third-generation cohorts of the Framingham Heart Study. Participants underwent multidetector computed tomography for CAC between 2002 and 2005 and were followed up for a median of 9.4 years for incident CVD.Statin eligibility was determined based on Framingham risk factors and low-density lipoprotein thresholds for ATP III, whereas the pooled cohort calculator was used for ACC/AHA.The primary outcome was incident CVD (myocardial infarction, death due to coronary heart disease [CHD], or ischemic stroke). Secondary outcomes were CHD and CAC (as measured by the Agatston score).Among 2435 statin-naive participants (mean age, 51.3 [SD, 8.6] years; 56% female), 39% (941/2435) were statin eligible by ACC/AHA compared with 14% (348/2435) by ATP III (P?<?.001). There were 74 incident CVD events (40 nonfatal myocardial infarctions, 31 nonfatal ischemic strokes, and 3 fatal CHD events). Participants who were statin eligible by ACC/AHA had increased hazard ratios for incident CVD compared with those eligible by ATP III: 6.8 (95% CI, 3.8-11.9) vs 3.1 (95% CI, 1.9-5.0), respectively (P<.001). Similar results were seen for CVD in participants with intermediate Framingham Risk Scores and for CHD. Participants who were newly statin eligible (n?=?593 [24%]) had an incident CVD rate of 5.7%, yielding a number needed to treat of 39 to 58. Participants with CAC were more likely to be statin eligible by ACC/AHA than by ATP III: CAC score >0 (n?=?1015): 63% vs 23%; CAC score >100 (n?=?376): 80% vs 32%; and CAC score >300 (n?=?186): 85% vs 34% (all P?<?.001). A CAC score of 0 identified a low-risk group among ACC/AHA statin-eligible participants (306/941 [33%]) with a CVD rate of 1.6%.In this community-based primary prevention cohort, the ACC/AHA guidelines for determining statin eligibility, compared with the ATP III, were associated with greater accuracy and efficiency in identifying increased risk of incident CVD and subclinical coronary artery disease, particularly in intermediate-risk participants.

Dataset Information

The Association of Coronary Artery Calcification With Subsequent Incidence of Cardiovascular Disease in Type 1 Diabetes: The DCCT/EDIC Trials.

Publications

The Association of Coronary Artery Calcification With Subsequent Incidence of Cardiovascular Disease in Type 1 Diabetes: The DCCT/EDIC Trials.

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