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Arterial Stiffness and Load Significantly Higher in Women Than Men With HFpEF

Key findings

  • This retrospective study evaluated differences in arterial stiffness and arterial load in 190 patients (107 women, 83 men) who had heart failure with preserved ejection fraction (HFpEF) diagnosed by invasive cardiopulmonary exercise testing
  • Resting measures of arterial stiffness and arterial load were significantly higher in women than in men with HFpEF
  • Ischemic predisposition as measured by the subendocardial viability ratio and tension time index was also significantly worse in women
  • Arterial stiffness was associated with abnormal left ventricular diastolic responses to exercise, particularly in women
  • Finding therapies that reduce arterial stiffness and load is a potential strategy for relieving exercise intolerance in patients with HFpEF, particularly women

Increased vascular stiffness has been implicated in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), as it interacts with ventricular–vascular coupling and diastolic function. Vascular stiffness is worse in women than men in the general population, and that difference has been proposed as an explanation for the female preponderance of HFpEF.

Massachusetts General Hospital researchers previously reported that women with HFpEF have worse hemodynamic profiles than men with HFpEF, including greater deficits in systolic and diastolic reserve and peripheral oxygen extraction. Emily Lau, MD, attending cardiologist, and Jennifer E. Ho, MD, formerly a cardiologist in the Heart Failure and Transplant Program at Mass General and now at Beth Israel Deaconess Medical Center, and colleagues have now built on those findings.

In a new analysis of patients with physiologically defined HFpEF, published in the Journal of Cardiac Failure, they found resting measures of arterial stiffness and arterial load were significantly higher in women than men and ischemic predisposition was worse in women.


The researchers retrospectively reviewed records of patients who underwent cardiopulmonary exercise testing for evaluation of dyspnea at Mass General between 2009 and 2017. The testing included invasive hemodynamic monitoring and invasive arterial stiffness measurements.

190 patients (107 women, 83 men) were identified who had chronic New York Heart Association class II–III symptoms, left ventricular ejection fraction ≥50%, and physiologic evidence of HFpEF.

Arterial Stiffness and Pulsatile Load

Resting and exercise systolic and diastolic blood pressure, and pulse pressure were similar in the two groups. Even so, after multivariable adjustment, women showed significantly greater arterial stiffness, greater vascular load, and worse ischemic predisposition than men (P<0.001 for all comparisons):

Arterial stiffness

  • Augmentation pressure (AP)—β, 0.72
  • Augmentation index (AIx)—β, 0.67
  • Aortic pulse pressure (AoPP)—β, 0.50

Arterial load

  • Total arterial compliance index (TACI)—β, −0.44
  • Pulse pressure amplification—β, −0.50

Ischemic predisposition

  • Subendocardial viability ratio (SEVR)—β, −0.57
  • Tension time index—β, 0.48

Arterial Stiffness and Abnormal LV Diastolic Reserve

In age-adjusted analyses, all resting measures of arterial stiffness were associated with abnormal left ventricular diastolic response to exercise. However, the relationships were more pronounced in women:

  • AP—Odds of abnormal response per 1-SD increase in AP: 3.16 in women (P=0.008) vs. 2.07 in men (P=0.15)
  • AIx—OR, 2.11 (P=0.04) vs. 1.93 (P=0.16)
  • AoPP—OR, 2.96 (P=0.01) vs. 1.86 (P=0.16)

Two additional parameters were significantly associated with abnormal diastolic exercise response in women and not men:

  • SEVR—OR, 0.41 (P=0.03) vs. 0.66 (P=0.24)
  • TACI—OR, 0.36 (P=0.01) vs. 0.58 (P=0.20)

Therapeutic Implications

Together with the previously published findings, these data offer a potential therapeutic target in a patient population that lacks effective therapies. The results are particularly noteworthy in light of two recent studies that linked exercise with a reduction in age-related aortic stiffness. Reducing arterial stiffness through exercise might improve symptoms in patients with HFpEF, particularly women.

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