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CAC measurements predict HFpEF risk in women
Literature - Sharma K, Al Rifai M, Ahmed HM, et al. - Am J of Cardiol 2017; published online ahead of print


The prevalence of HFpEF is increasing, affecting more women than men, and treatment options for this condition are limited [1,2]. The pathophysiology of HFpEF is complex, and efforts are made to target subgroups of patients with specific characteristics, who may need individual therapeutic approaches [3]. CAD is associated with elevated HFpEF risk, and HFpEF is seen in up to half of patients. Since CAC is a marker of coronary atherosclerosis [4], CAC measurements might be useful to identify individuals at high-risk for HFpEF, before they develop clinically overt CAD.

This analysis of the MESA study evaluated whether assessing CAC is helpful for the identification of patients at higher risk for HFpEF. Moreover, it was assessed whether the potential association between CAC and the risk of HFpEF is influenced by gender.

The MESA study recruited 6814 asymptomatic men and women without clinical CVD, aged 45-84 years, between 2000 and 2002 in the US. At baseline, each participant was assessed for the presence of CAC. All participants were scanned twice, and the average Agatston score was calculated and used for all analyses [5].

Main results

  • During the median follow-up time of 11.2 years, there were 127 incident HF hospitalizations.
  • The overall incidence rate of HFpEF was 1.82 per 1000 person-years (PY). Incidence rates were slightly higher for men compared to women (2.00 vs. 1.66 events per 1000 PY, respectively, P=0.29).
  • HFpEF incidence gradually raised as CAC scores increased: for CAC=0: 0.99 events per 1000 PY; for CAC 1-100: 1.48 events per 1000 PY; for CAC 101-300: 2.95 events per 1000 PY, and for CAC >300: 5.39 events per 1000 PY.
  • HFpEF risk was significantly higher in the CAC 101-300 and >300 group compared with CAC=0 (unadjusted HR: 2.99; 95%CI: 1.76-5.08; and HR: 5.50; 95%CI: 3.52-8.59, respectively, P for trend <0.001).
  • After adjustment, the differences were not significant any longer, but a trend remained for higher risk with increasing CAC (P=0.02).
  • There was a 4-fold increase in HFpEF risk for every 1 unit increase in log-transformed CAC, which was no longer significant after adjustment (HR: 1.12; 95%CI: 0.60-2.09).
  • There was a significant interaction between CAC and gender (P for interaction=0.03 for both continuous and categorical CAC).
  • After adjustment, CAC>300 in females was associated with a 2.81-fold increase in risk of HFpEF (95%CI: 1.32-5.95; P for trend <0.001).


In asymptomatic individuals without clinical CVD, the measurement of CAC was associated with the risk of HFpEF in women and may therefore be helpful for the risk stratification of HFpEF in women. These findings suggest that CAC may be used to identify and introduce appropriate preventive measures for women at high risk of HFpEF.


1. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006;355:251-259.

2. Bhatia RS, Tu JV, Lee DS, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 2006;355:260- 269.

3. Sharma K, Kass DA. Heart failure with preserved ejection fraction: mechanisms, clinical features, and therapies. Circulation research 2014;115:79-96.

4. Shah SJ. Evolving approaches to the management of heart failure with preserved ejection fraction in patients with coronary artery disease. Curr Treat Options Cardiovasc Med 2010;12:58-75.

5. Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of Coronary-Artery Calcium Using Ultrafast Computed-Tomography. J Am Coll Cardiol 1990;15:827-832.

Find this article online at Am J Cardiol

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Schedule27 May 2024