Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality

Abstract

Background Data regarding coronary artery calcification (CAC) prognosis in diabetic individuals are limited to 5-years follow-up. We investigated the long-term risk stratification of CAC among diabetics, compared to non-diabetic individuals. Methods and Results 9715 asymptomatic individuals undergoing CAC scoring were followed for a median (IQR) of 14.7 (13.9–15.6) years The incidence density rate and hazard ratios (HR) with 95% confidence intervals (95%CI) were used to calculate all-cause mortality. Incremental prognostic utility of CAC was evaluated using the area under the receiver operator characteristic curve (AUC) and net reclassification improvement (NRI). Diabetics (54.7±10.8 years; 59.4% male) comprised 8.3% of the cohort (n=810), of which 188 (23.2%) died. For CAC=0, the rate of mortality was similar between diabetic and non-diabetic individuals for the first 5 years (p>0.05), with a non-linear increased risk of mortality for diabetics after 5 years (p<0.05). The adjusted risk of death for those in the highest (CAC>400) versus the lowest (CAC=0) category of CAC increased by a hazards of 4.64 (95%CI=3.74–5.76) and 3.41 (95%CI=2.22–5.22) for non-diabetic and diabetic individuals, respectively. The presence of CAC improved discrimination (AUC range: 0.73–0.74, P<0.01) and reclassification (category-free NRI range: 0.53–0.50, P<0.001) beyond conventional risk factors in non-diabetic and diabetic respectively. Conclusions CAC=0 is associated with a favorable 5-year prognosis for asymptomatic diabetic and non-diabetic individuals. After 5 years, the risk of mortality increases significantly for diabetic individuals even in the presence of a baseline CAC=0.

All-cause and cause-specific mortality in individuals with zero and minimal coronary artery calcium: A long-term, competing risk analysis in the Coronary Artery Calcium Consortium

“…Subsequently, the 2018 and 2019 ACC/AHA Cholesterol and Prevention of CVD guidelines brought CAC = 0 to the forefront as a highly valuable tool for downgrading risk estimates in patients who would otherwise be considered candidates for chronic statin therapy [14,24]. The fact that in our cohort almost half of the study population had a CAC score of zero (which is consistent with reports from other cohorts [3][4][5][6][7][8][9][10]25]) supports the potential usefulness of CAC = 0 in a broad borderline/intermediate risk group.…”

“…Our group previously demonstrated a very low death rate -approximately 0.5% over 5 years-in a subset of the CAC Consortium population with CAC = 0 [3]. More recently, Valenti et al also found a very low mortality rate in asymptomatic individuals with CAC = 0 undergoing CAC scoring in a single US center extending to 15-year follow-up [4]. However, these two prior studies only assessed all-cause rather than case-specific mortality.…”

“…Once again, while our results may have a limited generalizability in unselected populations, they can be used to inform clinician-patient discussions of young adults undergoing CAC scoring in the US. Also, inclusion of a mostly White patient population in the CAC Consortium may also limit generalizability of the present findings to other racial/ethnic groups, although prior studies have shown that CAC = 0 is as predictive of optimal prognosis in other racial/ethnic groups [3][4][5][6][7][8][9][10][11][12][13]28].…”

“…There is increasing interest in zero coronary artery calcium (CAC) as a marker of sustained good health [1,2]. Prior studies have reported very low rates of coronary heart disease (CHD) events, cardiovascular disease (CVD) events, and all-cause mortality in the presence of a CAC score of zero (CAC = 0) [3][4][5][6][7][8][9][10][11][12]. Indeed, CAC = 0 appears to be the single strongest "negative risk factor" for incident CVD [13].…”

Coronary Artery Calcium Score for Long-term Risk Classification in Individuals With Type 2 Diabetes and Metabolic Syndrome From the Multi-Ethnic Study of Atherosclerosis

“…Their observed NRI was 0.19 despite use of more prognostic indicators than CAC score alone compared with FRS, which could be attributable to the shorter follow-up period requiring estimation vs measurement of 10-year CHD event rates. Valenti et al 35 also examined long-term risk prognostication for all-cause mortality using CAC scores in 810 individuals with diabetes from a single-site cohort. They reported a category-free NRI for all-cause mortality of 0.50 to 0.53 among those with diabetes, which is similar to our results for CHD events.…”