Greater HF Risk Reduction in Active Postmenopausal Women

News Author: Patrice Wendling; CME Author: Charles P. Vega, MD

Posted: 11/2/2018

Clinical Context

Exercise is promoted as a means to improve physical and mental health, but can exercise specifically reduce the risk for HF? Kenchaiah and colleagues assessed this subject in a study of the Physicians Health Initiative cohort, which was published in the January 6, 2009 issue of Circulation.[1] The study cohort included more than 21,000 male physicians and assessed the effects of BMI and physical activity on the risk for incident HF.

Over a mean follow-up period of 20.5±5.4 years, 1109 men developed HF. In multivariate analysis, each 1-kg/m2 increase in BMI was associated with an 11% increase in the risk for incident HF. The risk for HF in obese men was 180% higher than that found among men at normal weight. Body mass index was particularly important as a risk factor for HF among younger men and individuals without a history of diabetes.

Physical activity reduced the risk for HF, regardless of BMI. Vigorous physical activity was associated with an 18% lower risk for HF. Very frequent (5 to 7 times per week) vigorous physical activity was associated with a stronger reduction in the risk for HF compared with less frequent exercise.

This study supports exercise as a means to reduce the risk for incident HF; however, there has been less research into this area among women. The current study by LaMonte and colleagues addresses this issue.

Study Synopsis and Perspective

A new Women’s Health Initiative (WHI) analysis has shown a clear inverse relationship between physical activity, including walking, and the incidence of 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 theheart.org | 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.[2]

Investigators examined self-reported physical exercise and incident HF in 137,303 WHI participants, aged 50 to 79 years, and in a subset of 35,272 women with adjudicated HF subtype. Their mean age was 63.1±7.2 years.

Physical activity intensity and duration were self-reported and results divided into quartiles according to 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; P trend <.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, BMI, and atrial fibrillation diagnosis.

When analyzed as a continuous exposure, each 1-log MET-hour/week 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 3 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,” Dr 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,” he continued.

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 before an HF diagnosis were influenced by a heart attack, said Dr 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 — 3 to 4 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 Dr 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,[3] Mariell Jessup, MD, Leducq Foundation, Boston, Massachusetts, and Nosheen Reza, MD, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, noted 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 older than 18 years 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 wrote.

The editorialists gave 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 because of exposure misclassification in studies of self-reported physical activity.

Before using the results to support physical activity prescription in all older women, however, Drs 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,” Dr 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,” Dr 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 Dr LaMonte, who served on the guideline writing committee.

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

Study Highlights

  • The WHI enrolled postmenopausal women between 50 and 79 years of age who had no terminal illness. A total of 161,808 women were followed for incident hospitalizations for acute HF through December 2015.
  • Women who reported HF as a history of HF at baseline were excluded from the present analysis, as were those who could not walk one block without assistance.
  • The final sample of participants included 137,303 women, including 35,272 who had HF defined by preserved or reduced ejection fraction.
  • Participants reported on physical activity duration and intensity at baseline and during follow-up. These self-reports have been validated using accelerometer studies.
  • The main study outcome was incident HF hospitalizations. Self-reported HF hospitalizations were adjudicated by trained physicians. Reduced ejection fraction HF was defined by an ejection fraction of <45%.
  • Physical activity was the principal study variable. Researchers adjusted their analysis to account for sociodemographic, health habit, and medical variables
  • The mean age at baseline was 63.1±7.2 years, and most women in the study were white, well-educated, and either former or never smokers. Rates of diabetes and coronary heart disease were low, but more than one-third of women had hypertension.
  • The mean total of physical activity per week was 13 MET-hours, which is equivalent to approximately 13 hours per week of brisk walking. Walking was the most popular form of exercise overall.
  • 1.8% of the study cohort developed incident HF during a total of 1.2 million person-years of follow-up. Incidence rates of HFpEF and HFrEF were 2.1% and 1.3%, respectively.
  • HF incidence rates per 1000 person-years among women in the upper tertile of physical activity vs no activity were 1.8 vs 2.9 for any HF and 1.3 vs 1.7 for HFpEF. The respective rates of HFrEF were 0.8 vs 1.2.
  • The HR for HF was significantly reduced at >0 to 7.2 MET-hours per week (tertile 1 of physical activity), and it declined further with greater MET-hour totals. Each additional 1-log MET-hour per week of baseline physical activity was associated with a mean risk reduction of 9%, 8%, and 10% for any HF, HFpEF, and HFrEF, respectively.
  • Analyses focused on physical activity levels recorded during the follow-up period demonstrated slightly more robust results against HF compared with baseline levels.
  • The association between greater physical activity and lower risk for HF was stronger among younger women and women without a history of coronary heart disease.
  • Walking was evaluated separately and found to contribute to a lower risk for HF.

Clinical Implications

  • A previous epidemiologic study of male physicians by Kenchaiah and colleagues found that higher BMI was associated with a higher risk for HF, particularly among younger men and individuals without diabetes. Vigorous physical activity was also associated with a lower risk for HF, regardless of BMI.
  • The current study by LaMonte and colleagues, according to the WHI cohort, shows that modest levels of physical activity, including walking, can reduce the risk for HF among women. Longer duration or higher intensity of physical activity was associated with a stronger effect in reducing HF risk, and physical activity was effective in reducing HF with both preserved and reduced ejection fraction.
  • Implications for the Healthcare Team: HF is associated with significant morbidity, reduced quality of life, and mortality. The current study can help the healthcare team motivate women to step up their levels of physical activity.

References

  1. Kenchaiah S, Sesso HD, Gaziano JM. Body mass index and vigorous physical activity and the risk of heart failure among men. Circulation. 2009;119:44-52. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727738/. Accessed September 11, 2108.
  2. LaMonte MJ, Manson JE, Chomistek AK, et al. Physical activity and incidence of heart failure in postmenopausal women. JACC Heart Fail. 2018 Sep 5. doi: 10.1016/j.jchf.2018.06.020. [Epub ahead of print] http://heartfailure.onlinejacc.org/content/early/2018/09/06/j.jchf.2018.06.020. Accessed September 11, 2018. Article abstract.
  3. Jessup M, Reza N. Walking Away From Heart Failure. JACC Heart Fail. 2018 Sep 4. doi: 10.1016/j.jchf.2018.07.005. [Epub ahead of print] http://heartfailure.onlinejacc.org/content/early/2018/09/04/j.jchf.2018.07.005. Accessed September 11, 2018. Editorial abstract.

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