Greater Physical Activity May Significantly Reduce HF Risk in Postmenopausal Women

Patrice Wendling

September 11, 2018

A new Women's Health Initiative (WHI) analysis has shown a clear inverse relationship between physical activity, including walking, and the incidence of heart failure (HF) in postmenopausal women.

"To my understanding, this is the first and largest evaluation of physical activity that has shown a protective effect — at current guideline-recommended levels, I might add — not only on overall heart failure but specifically the two subtypes," lead author, Michael LaMonte, PhD, MPH, University at Buffalo, New York, told | Medscape Cardiology.

Prior studies evaluating HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) have tended to lack sufficient statistical power, and so results were inconclusive, he said. An analysis of 1142 Framingham Study participants found no significant association between physical activity and HFpEF or HFrEF, but it failed to report results for women, who are known to have a higher prevalence of HFpEF.

The current study was published in JACC Heart Failure on September 5.

Investigators examined self-reported physical exercise and incident HF in 137,303 WHI participants, age 50 to 79 years, and in a subset of 35,272 women with adjudicated HF subtype. Their mean age was 63 years.

Physical activity intensity and duration were self-reported and results divided into quartiles based on metabolic equivalent of task (MET) values multiplied by hours of participation per week. The average MET-hours/week was 13, with walking the most common activity (38%).

During a mean 14-year follow-up, 2523 incident cases of overall HF, 451 of HFrEF (EF < 45%), and 734 of HFpEF (EF ≥ 45%) occurred.

After controlling for sociodemographic factors, smoking, alcohol, hormone therapy, and hysterectomy, significant inverse associations were observed between total physical exercise and overall HF (hazard ratio [HR], 0.89; trend P < .001), HFpEF (HR, 0.93; P < .001), and HFrEF (HR, 0.81; P = .01).

The inverse associations remained after further adjustment for treated diabetes, treated hypertension, systolic and diastolic blood pressure, body mass index (BMI), and atrial fibrillation diagnosis.

When analyzed as a continuous exposure, each 1-log MET-hour/wk of baseline total physical activity was associated with a risk reduction on average of 9%, 8%, and 10% in overall HF, HFpEF, and HFrEF, respectively.

Notably, greater walking was significantly associated with lower risks for all three HF outcomes.

"Basically it boiled down to about 150 minutes per week of walking at a self-selected pace and that's pretty much spot on with the current federal guidelines," LaMonte said. "You could replace walking with other activities but 150 minutes per week of moderate-effort activities is where the general benefits are seen."

"We're very happy these findings now extend to heart failure, given its growing frequency in the population, its difficulty in treating, and the huge costs that it incurs not only economically but with human suffering."

Associations between total physical activity and HF endpoints were consistent across subgroups defined by age, BMI, diabetes, hypertension, physical function, and coronary heart disease diagnosis.

Another unique aspect of the study is a secondary analysis, using time-varying physical activity levels, that took into account whether changes in physical activity after the baseline assessment but prior to an HF diagnosis were influenced by a heart attack, said LaMonte.

"We were able to control for that statistically and we still saw that the physical activity at baseline was inversely related to heart failure risk by about 30% or so in women who were at guideline-recommended levels of walking in particular," he said.   

Finally, the secondary analysis showed a sharp dose-dependent relationship for incident HF, with a statistically significant inverse trend observed only between strenuous physical activity — three to four times above current guideline recommendations — and HFpEF.

"That's encouraging because some women are able and interested in doing more than just the minimum current guideline recommendations," and a "small number of studies have shown an uptick in risk for certain cancers and ischemic heart disease at extreme levels of activity," said LaMonte.

"I know it's a cliché to say, but if these findings are confirmed by a randomized trial, an ounce of prevention truly is worth a pound of cure," he said. "It's much, much harder to regain health after it's lost than it is to try and maintain it over the life course."

"Unfortunately, we live in a time where it's just too easy to put Band-Aids on problems by way of pills and other medical procedures and we lose sight of prevention."

In an accompanying editorial, Mariell Jessup, MD, Leducq Foundation, Boston, Massachusetts, and Nosheen Reza, MD, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, note that the HF incidence rate in white women triples with each 10-year age increase between ages 65 to 74 and 75 to 84 and that HF incidence, risk factor prevalence, and mortality rates are not uniform across ethnic groups. Moreover, more than 8 million people over age 18 are expected to be living with HF by 2030.

"As our understanding of the demographics and differences" in HFpEF and HFrEF "evolves, we must incorporate these nuances into evaluating and implementing population-level interventions targeted toward disease prevention," they write.

The editorialists give a tip of the hat to the "clever" secondary analysis, which they say corroborates prior findings of a dose-dependent relationship between physical activity and incident HF. It also mitigates the inevitable bias due to exposure misclassification in studies of self-reported physical activity.

Before using the results to support physical activity prescription in all older women, however, Jessup and Reza point out several caveats, including a lack of information on the model selection strategies and lack of detailed output parameters from the models. The latter makes it difficult to understand the statistical and clinical significance of component covariates, or the overall degree to which data are over- or underfit, which has "potential implications for the external validity of the findings."

Another limitation is the omission of additional potential mediating factors, such as interim atrial fibrillation, diabetes, hypertension, and the lack of a direct measure of cardiorespiratory fitness.

"We did look at interim heart attack, but we totally agree with Dr Jessup that a fuller, more complete understanding of what the mechanisms — through which physical activity may be conferring a heart failure benefit are — would have been possible if we had the information on those outcomes, but we didn't have that at our disposal," LaMonte said.

As to the model selection, he said, "There's probably more than one way to skin the cat, if you will, but I'm sure if we could redo the analysis two to three different ways, the vantage point might change but I think the conclusion would stay the same."

"The final message? That's an easy one: sit less and move more, and gradually increase movement toward the guideline recommendations," LaMonte said. "It's an investment in the future, just like investments we make in other aspects of our life, and it's a very powerful tool for prevention."

An update to the federal 2008 Physical Activity Guidelines for Americans should be released by the end of 2019 and will include roughly the same activity levels but will also emphasize sitting less, according to LaMonte, who served on the guideline writing committee.

Reza is supported by a National Institutes of Health award in genomic medicine. The authors and Jessup report no relevant financial relationships.

JACC Heart Fail. Published online September 6, 2018. Abstract, Editorial

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