Source: Philips Healthcare

Coronary artery calcification (CAC) has a clear association with the risk of heart failure (HF), independent of overt coronary heart disease (CHD), according to the Rotterdam Study published in the September issue of the Journal of the American College of Cardiology: Cardiovascular Imaging. Based on these findings, the editorialists suggested that CAC may be an “important additional component of the algorithm to predict HF.”

HF is often observed as a first manifestation of coronary atherosclerosis rather than a sequela of overt CHD, noted the study authors. “Although numerous studies have shown that CAC, an established measure of coronary atherosclerosis, is a strong predictor of CHD, the association between CAC and future heart failure has not been studied prospectively,” they wrote.

In the Rotterdam Study, a population-based cohort, 1,897 asymptomatic participants (mean age, 69.9 years; 58 percent women) underwent CAC scoring and were followed for the occurrence of heart failure and CHD.

In this prospective study among elderly subjects, Maarten J. G. Leening, MD, MSC, of the departments of cardiology and epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues investigated the association between CAC, as detected by electron-beam CT and the risk of heart failure and examined whether this relationship is independent of incident overt CHD during follow-up.

During a median follow-up of 6.8 years, there were 78 cases of heart failure and 76 cases of nonfatal CHD. After adjustment for cardiovascular risk factors, increasing CAC scores were associated with heart failure, with a hazard ratio of 4.1 for CAC scores more than 400 compared with CAC scores of 0 to 10, according to the authors.

After censoring participants for incident nonfatal CHD, the investigators reported that the increasing extent of CAC remained associated with heart failure, with a hazard ratio of 2.9 for CAC scores of more than 400. Moreover, adding CAC to cardiovascular risk factors resulted in an optimism-corrected increase in the c-statistic by 0.03 to 0.734, and substantially improved the risk classification of subjects (continuous net reclassification index = 34 percent).

In this study, HF represented 40 percent of the first cardiac events observed, which reinforces the numbers from a recent report of the Framingham Heart Study showing in an elderly subpopulation that 48 percent of the participants with a cardiac event had heart failure as their initial presentation (Circulation 2010;121:505-511).

“The strengths of our study include the standardized measurements of cardiovascular risk factors in a population-based setting with long and virtually complete follow-up,” the Rotterdam Study investigators wrote. “Furthermore, due to the fact that both participants of our study and their treating physicians were not informed about the CAC scores, our cohort is one of few in the world in which an unbiased association between CAC and future HF can be investigated.”

The authors acknowledged some limitations as well, including that the results in this elderly population might not translate to younger patients and the additional information (beyond occurrence of HF symptoms) on the presence of objective cardiac dysfunction was not present in all cases.

Because heart failure is highly prevalent in the elderly, Leening et al recommended that “it might be worthwhile to include HF as an outcome in future risk assessment programs incorporating CAC.”

“Remarkably, when corrected for age, sex and standard cardiovascular risk factors and censoring subjects with incident nonfatal CHD, a three-fold increased risk of HF remained, suggesting an association between CAC and HF separate from overt coronary disease in this population,” study editorialists Anjali Tiku Owens, MD, and Mariell L. Jessup, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, wrote about the findings.

Owens and Jessup also noted the findings shouldn’t be generalized to a younger population or one that is more racially diverse, such as the U.S. population.

Finally, Owens and Jessup said the larger questions for future studies are: “How do we lessen this risk, above and beyond treatment of standard cardiovascular risk factors? Will our interventions depend on the type of HF (systolic or diastolic) that is involved?” They concluded that the cardiovascular community needs “not only an accurate model for prediction, but also proven methods to mitigate the hazard, with a widespread application of prevention measures to our diverse U.S. population.”

This study is supported by grants from the Netherlands Organisation for Scientific Research and The Netherlands Organisation for Health Research and Development and the Netherlands Heart Foundation. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University in Rotterdam; The Netherlands Organisation for the Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission; and the Municipality of Rotterdam. None of the funders had any role in design and conduct of the study, according to the investigators.