Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study

Objective To evaluate the predictive value of abdominal aortic calcium (AAC) for incident cardiovascular disease (CVD) independent of coronary artery calcium (CAC). Approach and Results We evaluated the association of AAC with CVD in 1974 men and women aged 45 to 84 years randomly selected from the Multi-Ethnic Study of Atherosclerosis participants who had complete AAC and CAC data from computed tomographic scans. AAC and CAC were each divided into following 3 percentile categories: 0 to 50th, 51st to 75th, and 76th to 100th. During a mean of 5.5 years of follow-up, there were 50 hard coronary heart disease events, 83 hard CVD events, 30 fatal CVD events, and 105 total deaths. In multivariable-adjusted Cox models including both AAC and CAC, comparing the fourth quartile with the ≤50th percentile, AAC and CAC were each significantly and independently predictive of hard coronary heart disease and hard CVD, with hazard ratios ranging from 2.4 to 4.4. For CVD mortality, the hazard ratio was highly significant for the fourth quartile of AAC, 5.9 (P=0.01), whereas the association for the fourth quartile of CAC (hazard ratio, 2.1) was not significant. For total mortality, the fourth quartile hazard ratio for AAC was 2.7 (P=0.001), and for CAC, it was 1.9, P=0.04. Area under the receiver operating characteristic curve analyses showed improvement for both AAC and CAC separately, although improvement was greater with CAC for hard coronary heart disease and hard CVD, and greater with AAC for CVD mortality and total mortality. Sensitivity analyses defining AAC and CAC as continuous variables mirrored these results. Conclusions AAC and CAC predicted hard coronary heart disease and hard CVD events independent of one another. Only AAC was independently related to CVD mortality, and AAC showed a stronger association than CAC with total mortality.

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“…17–21 Of interest, a recent report from the Framingham study showed that AAC, but not CAC, was significantly associated with total mortality. 28 …”

Section: Discussionmentioning

confidence: 99%

Abdominal Aortic Calcium, Coronary Artery Calcium, and Cardiovascular Morbidity and Mortality in the Multi-Ethnic Study of Atherosclerosis

Criqui

Denenberg

McClelland

et al. 2014

ATVB

114

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“…6 Epidemiologic studies demonstrated a graded increase in the risk of cardiovascular events across strata of CAC scores. 2–4 However, Agatston score does not account for CAC distribution and does not include information on the involvement of individual coronary arteries and on the involvement of proximal and distal segments. The results of studies using coronary CT angiography showed a strong association of coronary atherosclerosis burden, typically expressed as number of coronary arteries or segments with plaque, with adverse outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…The cardiovascular outcomes were defined in the Framingham Heart Study previously. 4,18 For the purpose of this study, major CHD events included recognized myocardial infarction and death from coronary heart disease. In the Framingham Heart Study, all study participants were under continuous surveillance for the development of outcomes.…”

Section: Methodsmentioning

confidence: 99%

“…1 The presence and amount of CAC are strong predictors of cardiovascular events. 2–4 CAC scoring provides significant improvement over traditional cardiovascular risk scores in risk discrimination and reclassification. 3,4 The amount of CAC is associated with the overall burden of coronary atherosclerosis, including both calcified and non-calcified plaque.…”

Section: Introductionmentioning

confidence: 99%

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Coronary Artery Calcium Distribution Is an Independent Predictor of Incident Major Coronary Heart Disease Events

Ferencik

Pencina

Liu

et al. 2017

Circ: Cardiovascular Imaging

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Background The presence and extent of coronary artery calcium (CAC) are associated with increased risk for cardiovascular events. We determined whether information on the distribution of CAC and coronary dominance as detected by cardiac computed tomography (CT) were incremental to traditional Agatston score (AS) in predicting incident major coronary heart disease (CHD). Methods and Results We assessed total AS and the presence of CAC per coronary artery, per segment and coronary dominance by CT in participants from the Offspring and Third generation cohorts of the Framingham Heart Study. The primary outcome was major CHD (myocardial infarction or coronary heart disease death). We performed multivariable Cox proportional hazards analysis and calculated relative integrated discrimination improvement (rIDI). In 1268 subjects (mean age 56.2±10.3 years, 63.2% men) with AS >0 and no prior history of major CHD, a total of 42 major CHD events occurred during median follow of 7.4 years. The number of coronary arteries with CAC (hazard ratio: 1.68 per artery, 95% CI 1.10–2.57, p=0.02) and the presence of CAC in the proximal dominant coronary artery (HR 2.59, 95% CI 1.15–5.83, p=0.02) were associated with major CHD events after multivariable adjustment for Framingham risk score and categories of AS. In addition, measures of CAC distribution improved discriminatory capacity for major CHD events (rIDI 0.14). Conclusions Distribution of coronary atherosclerosis, especially CAC in the proximal dominant coronary artery and an increased number of coronary arteries with CAC, predict major CHD events independently of the traditional AS in community-dwelling men and women.

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“…Prior studies in the Framingham Cohort have shown the presence of AAC, as seen on plain radiographs and MDCT scans, in middle-aged men and women, was associated with increased incidence of CVD, coronary heart disease (CHD), heart failure (HF), and cardiovascular and all-cause mortality. 22,23,24 Thus, the presence of extra-coronary calcium such as AAC could be an early marker of the likelihood of CAC progression and can further identify a subgroup of asymptomatic individuals who may be at increased risk of adverse CVD outcomes. Given the increased use of abdominal CT imaging in routine medical care, abdominal calcium is increasingly reported as an incidental finding and may have added clinical utility.…”

Section: Discussionmentioning

confidence: 99%

Relation of Risk Factors and Abdominal Aortic Calcium to Progression of Coronary Artery Calcium (from the Framingham Heart Study)

Onuma

Pencina

Qazi

et al. 2017

The American Journal of Cardiology

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Coronary artery (CAC) and abdominal aortic calcium (AAC) on multi-detector computed tomography (MDCT) permit assessment of the presence and burden of coronary and systemic atherosclerosis. Risk factors for progression of CAC and AAC, and the association of AAC with CAC progression have not been well characterized in a community-dwelling cohort. We studied 1,959 asymptomatic participants from the Framingham Heart Study who underwent serial MDCT scan with a median interval of 6.1 years. Primary outcomes were: (a) the incidence of coronary and abdominal aortic calcium (CAC > 0 and AAC > 0 with baseline CAC = 0 and AAC = 0; and (b) absolute progression of CAC (CAC > baseline CAC and AAC > baseline AAC). Covariates were collected at adjacent cycle exams, and included; age, sex, use of antihypertensive therapy, use of lipid-lowering therapy, cigarette smoking, and total and HDL cholesterol. Predictors for CAC and AAC progression included: baseline CAC, baseline AAC, lipid-lowering therapy, diabetes, HDL cholesterol, BMI, and serum creatinine. Multivariable stepwise logistic and linear regression models were used to test the association of these risk factors with CAC and AAC. Those who developed incident CAC on follow-up scanning comprised 18.8% of 1,124 participants, and 84.9% of 780 participants, with detectable baseline CAC, had further progression. Baseline AAC was a predictor of both CAC incidence and progression, independent of other risk factors. In stepwise models, addition of baseline AAC slightly improved the area under the curve (AUC) from 0.72 (0.68, 0.76) to 0.74 (0.70, 0.78). In conclusion, standard cardiovascular disease (CVD) risk factors are associated with incidence and progression of CAC and AAC, and AAC augments CAC incidence and progression above CVD risk factors.

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Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study

Cited by 176 publications

References 32 publications

Abdominal Aortic Calcium, Coronary Artery Calcium, and Cardiovascular Morbidity and Mortality in the Multi-Ethnic Study of Atherosclerosis

Abdominal Aortic Calcium, Coronary Artery Calcium, and Cardiovascular Morbidity and Mortality in the Multi-Ethnic Study of Atherosclerosis

Coronary Artery Calcium Distribution Is an Independent Predictor of Incident Major Coronary Heart Disease Events

Relation of Risk Factors and Abdominal Aortic Calcium to Progression of Coronary Artery Calcium (from the Framingham Heart Study)

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