Physical Activity for Cardiovascular Risk Factor Reduction

“Strong evidence demonstrates a significant relationship between greater amounts of physical activity and decreased incidence of cardiovascular disease, stroke, and heart failure.”

Astute readers, or those who enjoy history as much as their columnist, will recognize the names Richard Doll and Sir Austin Bradford Hill. Their research, first published in 1950 in the British Medical Journal, demonstrably linked cigarette smoking to an increased risk of lung cancer. ¹ Especially astute readers will recall that other notable research was occurring at the same time in the same city. Jeremy Morris and colleagues at London Hospital were investigating the association between occupational physical activity and coronary heart disease. Although their 1953 Lancet publications^2,3 may not be quite as famous as those of Doll and Hill, they were equally revolutionary in demonstrating that lifestyle behaviors influence cardiovascular risk.

Morris and colleagues reviewed the medical records of middle-aged Londoners who were employed as either transportation workers or postal and civil workers. They selected these two occupational categories because each comprised more and less physically active workers. Within transportation were (1) the conductors, who spent their working hours walking up and down the steps of double-decker buses, and (2) the drivers, who spent their working hours mostly sitting. The postal and civil services occupation included (1) a highly active group of postmen, who walked much of the day; (2) an intermediately active group comprising postal supervisors and telegraph officers; and (3) a largely sedentary group comprising clerks, executives, and telephonists.

For each occupational category, the researchers found that more physically active workers experienced a statistically lower incidence of coronary heart disease. Among transportation workers, the more active conductors had an incidence of 1.9 cases per 1000 person-years, compared to 2.7 cases per 1000 person-years among drivers. Within the postal and civil services category, a dose response emerged: Incidence was 1.8 in the most active group, 2.0 in the intermediately active group, and 2.4 in the least active group.

Across the pond in the United States, Ralph Paffenbarger, lead investigator of the Harvard Alumni Health Study, was embarking on a cohort study of San Francisco longshoremen. Using similar methodology as their British peers, Paffenbarger and colleagues divided the longshoremen into a more active group (including stevedores, shovelers, and cargo handlers) and a less active group (such as those in clerical and supervisory roles). Over two decades of follow-up, the more active employees had statistically lower mortality rates from coronary heart disease and stroke.^4,5

These early epidemiologic studies laid a solid foundation, on which has been built a massive edifice of irrefutable research. Study after study has demonstrated that aerobic and muscle-strengthening physical activity lowers the incidence of and mortality from cardiovascular disease. The Scientific Advisory Committee for the 2018 Physical Activity Guidelines summarized the evidence for cardiovascular mortality with three major evidence statements, which are worth repeating here verbatim. ⁶

• • Strong evidence demonstrates that a strong inverse dose–response relation exists between amount of moderate-to-vigorous physical activity and cardiovascular disease mortality. The strength of the evidence is very unlikely to be modified by more studies of this outcome.

• • Strong evidence demonstrates that the shape of the curve is nonlinear, with the greatest benefit seen early in the dose–response relationship. The relationship of moderate-to-vigorous physical activity and risk reduction has no lower limit. Risk appears to continue to decrease with increased exposure up to at least three to five times the amounts of moderate-to-vigorous physical activity recommended in the 2008 Guidelines (i.e., 150 minutes per week). The new data are consistent with those used to develop the 2008 Guidelines.

• • Strong evidence demonstrates that these relationships do not vary by age, sex, race, or weight status.

To state it more bluntly, the strength of this evidence makes it highly improbable that future studies would undermine it. For cardiovascular disease incidence, the Committee found similar evidence, although in 2018 they could not conclude that these relationships persist across demographic strata and body weight categories. Again, we cannot improve by paraphrasing their summary statements:

• • Strong evidence demonstrates a significant relationship between greater amounts of physical activity and decreased incidence of cardiovascular disease, stroke, and heart failure. The strength of the evidence is unlikely to be modified by more studies of these outcomes.

• • Strong evidence demonstrates a significant dose–response relationship between physical activity and cardiovascular disease, stroke, and heart failure. When exposures are expressed as energy expenditure (MET-hours per week), the shape of the curve for incident CVD (cardiovascular disease) appears to be nonlinear, with the greatest benefit seen early in the dose–response relationship. It is unclear whether the shapes of the relations for incident stroke and heart failure are linear or nonlinear. There is no lower limit for the relation of MVPA (moderate-to-vigorous physical activity) and risk reduction. Risk appears to continue to decrease with increased exposure up to at least five times the current recommended levels of moderate-to-vigorous physical activity.

• • Insufficient evidence is available to determine whether these relationships vary by age, sex, race, ethnicity, socioeconomic status, or weight status.

The scientific advisory report explains that this is likely mediated by the salubrious effect of physical activity on blood pressure, serum lipid levels, hemoglobin A1C, and body composition, among other factors. In other words, known metabolic and biochemical pathways offer a plausible throughline, with more under investigation.

This is not to suggest that the benefit of physical activity is limited to cardiovascular disease outcomes. Within the past decade, it has become clear that this benefit extends even to infectious disease outcomes. For those of us who have followed the growing field of physical activity and immune health, it was not altogether shocking when Sallis and colleagues published a study in 2021 describing physical inactivity as a risk factor for severe outcomes and death associated with COVID-19. This study originated at Kaiser Permanente of Southern California, a large health care system that routinely collects physical activity information as a “vital sign” during clinical visits.

Among nearly 50 thousand patients who had documented infection with SARS-CoV-2 virus, the investigators found that individuals who were consistently inactive or inconsistently active before infection were much more likely to be hospitalized than their active peers, after adjusting for several factors. In fact, physical inactivity was a greater risk factor for COVID-19 hospitalization than either current smoking or obesity. Whereas individuals with obesity had a 77% greater risk of hospitalization compared to those with a normal body mass index, individuals who had routinely reported physical inactivity experienced a 230% greater risk of hospitalization compared to their peers who were consistently active, adjusted for demographics, underlying medical conditions, and other appropriate confounders. ⁷ A subsequent meta-analysis compiling data from 16 studies and over 1.8 million adults conveyed similar findings, ⁸ prompting the Centers for Disease Control and Prevention to add physical inactivity to its list of risk factors for severe COVID-19. ⁹

Shortly thereafter, another study reported that physical activity appears protective against influenza and pneumonia mortality. Among nearly 600 thousand U.S. adults followed for a median of 10 years, those who had met the aerobic and muscle-strengthening guidelines (per the U.S. Physical Activity Guidelines ¹⁰ ) experienced a 48% lower risk of influenza and pneumonia category compared to their peers who had met neither guideline, after adjusting for sociodemographic factors, body mass index, presence of comorbidities, vaccination status, and other lifestyle factors. ¹¹ As exciting as these results may have been, they were not entirely novel. Indeed, Paffenbarger’s longshoremen gave a clue several decades ago. Of the 29 pneumonia deaths recorded during 22 years of follow-up, 27 occurred among the less physically active workers. ⁵

Sometimes medical evidence becomes so overwhelming that it imperceptibly shifts from vital and revolutionary to obvious and mundane. And when it becomes mundane, it can be neglected, as we have seen with measles vaccination coverage and other seemingly resolved issues. It is incumbent upon readers of this journal to keep our eye on the ball, so to speak, and to continue promoting physical activity in our families, practices, and communities.