Calcium score is important in adults with diabetes and metabolic syndrome

The MESA study uncovered the significance of coronary artery calcium (CAC) score in predicting coronary events among adults with diabetes and metabolic syndrome. About 7,000 individuals without baseline CVD were followed for 11 years.

Authors found that calcium score was more important than severity or duration of diabetes in identifying patients at higher risk for coronary heart disease. CAC score was equally useful in those with metabolic syndrome and without diabetes. 

In the future I anticipate CAC score to be incorporated in the ASCVD risk calculator as an independent predictor. Such a calculator is provided by the American College of Cardiology and American Heart Association (click here). It estimates the risk of an ASCVD event in 10 years based on person's age, gender, race, cholesterol, blood pressure and history of diabetes and smoking.



Also see:

Metformin and calcium score in prediabetes

Metformin and CVD prevention


JAMA Cardiology

Risk Classification (MESA)

November 2017

Importance: Although the risk of type 2 diabetes is considered to be equivalent to coronary heart disease (CHD) risk, there is considerable heterogeneity among individuals for CHD and atherosclerotic cardiovascular disease (ASCVD) risk.

It is not known whether coronary artery calcium (CAC) assessment at baseline in individuals with established metabolic syndrome (MetS) or diabetes identifies CHD and ASCVD prognostic indicators during a long follow-up period.

Objective: To compare improvement in long-term prognostication of incident CHD and ASCVD using CAC scores among those with diabetes, MetS, or neither condition.

Design, Setting, and Participants:  This study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of 6,814 males and females aged 45-84 years without known CVD from 4 race/ethnicity groups (white [38.5%], African American [27.5%], Hispanic [22.1%], and Chinese [11.9%]) recruited from 6 US communities from July 2000 through August 2002.

Follow-up for each participant extended to the first occurrence of an incident event, other death, loss to follow-up, or the last follow-up call through December 31, 2013. Data analysis was performed from June 1, 2016, to September 12, 2017. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). Area under the receiver operator characteristic curve and net reclassification improvement were used to compare incremental contributions of CAC score when added to the Framingham risk score, ethnicity/race, and socioeconomic status.

Main Outcomes and Measures: CHD events, including myocardial infarction, resuscitated cardiac arrest, or CHD death.

Results: Of 6,814 MESA participants, 6,751 had complete risk factor and follow-up data and were included in this study (mean age, 62.2 years; 47.2% male). A total of 881 (13.0%) had diabetes, 1738 (25.7%) had MetS, and 4132 (61.2%) had neither condition.

After 11.1 mean years of follow-up, CHD events occurred in 84 participants with diabetes (135 ASCVD events), 115 with MetS (175 ASCVD events), and 157 with neither (250 ASCVD events).

The CAC score was independently associated with incident CHD in multivariable analyses in those with diabetes (HR, 1.30, p<0.05), MetS (HR, 1.30, p<0.05), and neither condition (HR, 1.37, p<0.05).

For incident CHD, net reclassification improvement with addition of CAC score was 0.23 (p<0.05) in those with diabetes, 0.22 (p<0.05) in those with MetS, and 0.25 (p<0.05) in those with neither condition.

The CAC score was also a prognostic indicator of CHD and ASCVD after controlling for diabetes duration of 10 years or longer at baseline, insulin use, and glycemic control.

Conclusions and Relevance: In a large multiethnic cohort, the addition of CAC score to global risk assessment was associated with significantly improved risk classification in those with MetS and diabetes, even if diabetes duration was longer than a decade, suggesting a role for the CAC score in risk assessment in such patients.

More from the publication:

Type 2 diabetes mellitus and metabolic syndrome (MetS) result in a cascade of metabolic derangement, predisposing individuals to not only subclinical atherosclerosis but also coronary heart disease (CHD) and atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC) measured by noncontrast computed tomography (CT) is a measure of subclinical atherosclerosis. Others have found that the presence, extent, and progression of CAC enables prognostication of adverse clinical events better than traditional risk factors and global risk scoring among asymptomatic individuals, and helps reclassify individuals at intermediate risk to low- or high-risk groups.

However, most prior studies that examined risk classification have excluded those with diabetes because the diagnosis of diabetes carries a label of CHD risk equivalency, whereas prediction models offer less clinical utility.

Although the risk of diabetes is considered to be CHD risk equivalent, studies have found that there is heterogeneity among individuals for CHD and ASCVD risk. Although studies examining the prognostic significance of CAC in diabetes have found an association of CAC with CHD and CVD events, these analyses have not focused on reclassifying individuals with diabetes and MetS into lower- or higher-risk groups for long-term CHD and CVD risk.

We investigated the utility of CAC scores in reclassifying asymptomatic individuals with diabetes and MetS and the association of CAC scores with long-term risk prognostication in a multiethnic, population-based study. In addition, we examined whether other factors, such as duration of diabetes, are associated with risk prognostication to aid in clinical decision making regarding screening for subclinical disease in patients with diabetes.

Our results indicate that evaluation of subclinical atherosclerosis with CAC scoring identifies downstream CHD and ASCVD events by more than a decade after screeening has been done regardless of the presence of diabetes or MetS. Coronary artery calcium scores can be used to identify lower- and higher-risk individuals with MetS and diabetes. Many individuals with diabetes are at lower CHD and ASCVD risk than is widely understood and are not at high risk or CHD risk equivalents. Our results also indicate that CAC scoring adds significant clinical utility in further stratifying and reclassifying risk in persons with MetS and diabetes beyond global risk assessment using the FRS or ASCVD Pooled cohort risk score.

Moreover, we found that the severity of CAC appears to be a more important clinical prognostic indicator than measures of disease severity, such as insulin use, glycemic control, and diabetes duration.



Although many prior studies have excluded those with diabetes based on assumptions that diabetes already confers CHD risk equivalence,

our findings indicate that 44.8% of those with MetS and 37.3% of those with diabetes have no evidence of CAC at baseline, associated with observed 10-year CHD event rates of only 2.3% among those with MetS and 3.7% among those with diabetes.

Thus, the “warranty period” of a CAC score of 0, as previously discussed, can be extended to 10 years in those with MetS or diabetes. Moreover, in our adjusted analyses, a CAC score of 0 was associated with low CHD and ASCVD risk among those with diabetes that was independent of diabetes duration, insulin use, or glycemic control.

Previous studies have emphasized the importance of diabetes duration, with the Framingham Heart Study reporting a 1.4-fold greater risk of CHD and a 1.9-fold greater risk of cardiovascular death for each 10-year increase in diabetes duration and the British Regional Heart Study reporting diabetes risk to be equivalent to CHD risk only in patients with a diabetes duration of 10 years or greater. In addition, the Veterans Affairs Diabetes Trial found that there was a greater risk of cardiovascular events despite tight glycemic control in patients with longer diabetes duration. As a result, the American Diabetes Association does not recommend aggressive hyperglycemia management in those with longer duration of diabetes and suggests that the duration of diabetes be considered when setting glycemic goals.

Our analysis indicates that the presence and extent of CAC are more associated with ASCVD risk than is diabetes duration. Even among patients with long-standing diabetes, the absence of CAC was associated with similar low risk of events as among those with shorter duration of diabetes.

Although diabetes is known to accelerate the aging process, future studies need to focus on the factors that provide resilience among patients with lack of subclinical disease despite long-standing diabetes.

Our results extend the findings of prior publications that have reported the clinical utility of CAC scoring, indicating that after a decade of follow-up, there is no decrement in the NRI among individuals without diabetes. Among those with diabetes, when we compared CAC scores with FRS and PCE for prognostication of long-term events, almost half of these individuals were reclassified to a different risk group. Yeboah et al reclassified CHD risk exclusively among those with diabetes after a follow-up of 8.5 years, combining data from a subset of participants in MESA and the Heinz Nixdorf Recall Study, who in addition to CAC scoring had undergone assessment of carotid intimal media thickness, measurement of ankle brachial index, and C-reactive protein testing. 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 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. However, that analysis did not adjust for markers of diabetes severity or duration.

Strengths of MESA include its large sample size, ethnic diversity, and community-based recruitment. The prospective design provides information on the temporal association between the presence and extent of CAC and subsequent CHD and ASCVD events. Limitations of our analysis include the lack of data on diabetes duration for the entire diabetes group. In addition, it was beyond the scope of our project to examine the effects of CAC progression or to consider the effects of time-varying covariates. Thus, our risk estimates relate to our baseline measures only and do not consider the possible effects of changes in CAC scores or other risk factors. Although the CAC score increases consistently with time and more rapidly in individuals with vs without diabetes, with greater progression portending additional risk as previously reported, baseline CAC score appears to be more accurate for prediction of events in persons with and without MetS and diabetes. In addition, participants in MESA and their primary physicians were informed of their CAC imaging results in a letter. It is possible that such information may have biased the results toward fewer incident events because of risk factor modification; however, this bias would result in attenuation of our findings.

Our results support the clinical utility of CAC scoring in those with diabetes and MetS. Currently, CAC imaging has a class IIb recommendation in the 2013 ASCVD risk assessment guidelines. In addition, the Imaging Council of the American College of Cardiology recently concluded that CAC screening is the most sensitive noninvasive risk stratification tool among asymptomatic persons with diabetes. Although screening for CHD in patients with diabetes has previously been found to not be of benefit in reducing CHD and ASCVD events, other reports have found that patient awareness of an abnormal CAC score and coronary CT angiography results is associated with increased adherence to preventive therapies, lifestyle changes, and improvement in lipid levels and other risk factors, suggesting that CAC screening might help to support behavioral modification.

n addition, Nasir et al found that CAC screening in MESA participants without diabetes can help identify those at adequately high risk who would benefit from statin therapy (and those at low risk who would not benefit). Whether asymptomatic patients with or without diabetes will have lower cardiovascular event rates from targeting statin use or intensity according to the presence of subclinical atherosclerosis has yet to be determined.

Future research should examine whether newer antidiabetic medications, such as sodium glucose cotransporter 2 inhibitors or glucagonlike peptide 1 receptor agonists, that benefit patients with known ASCVD could be considered for those at increased risk based on extent of CAC or other measures of subclinical atherosclerosis. Prospective studies that focus treatment intensity on objective measures of subclinical atherosclerosis may improve personalization of preventive therapies.