CV Risk Factors in Youth May Prove Indelible for Later CAD

Adults with elevated blood pressure and LDL cholesterol levels before age 40 appear to have increased rates of cardiovascular disease in later life, according to a pooled analysis of six large cohort studies that accounted for subsequent risk factor exposure.

Having an LDL cholesterol level of 100 mg/dL or greater in young adulthood, for example, was associated with a relative 64% increase in the risk of coronary heart disease (CHD). Similarly, elevations in both systolic and diastolic BP in young adults were associated with greater risks of heart failure over the long term.

Critically, these relationships held regardless of risk factor exposures later in life, Yiyi Zhang, PhD (Columbia University, New York, NY), and colleagues report.

The findings, published online ahead of the July 23, 2019, issue of the Journal of the American College of Cardiology, “suggest that exposures to elevated systolic BP, diastolic BP, and LDL during young adulthood contribute independently to later life CHD and heart failure risks,” the researchers conclude.

That’s an important new observation: while other studies have linked early adulthood exposure to later cardiovascular disease, they have not necessarily been able to tease out the relative impact of early versus later risk factor exposure, the authors note.

As such, the findings have implications for the timing of primary prevention interventions, which tend to be implemented in older adulthood, and for study follow-up.

One challenge physicians are likely to face in trying to push preventive efforts into earlier adulthood is that younger patients believe their risks of cardiac events are small and/or something that can be fully addressed later in life, senior author Andrew E. Moran, MD (Columbia University), indicated.

“Most young adults have an attitude that ‘I can wait, nothing’s going to hurt me in the short term, put it off, become more healthy when I’m older.’ And a lot of people do make that change later in their lives,” Moran told TCTMD. “But the message from this paper is: You know what? Making those changes later in your life will not reverse the unhealthy choices you made when you were younger. There’s no reason to wait.”

Timing is Everything

Moran noted that studying the long-term consequences of risk factor exposures early in life can be difficult. “Most studies, especially in the United States—whether they’re clinical trials or observational studies—tend to have a short time horizon,” he said. And another challenge, he added, is that some cohort studies only begin tracking people in midlife or later, meaning there is no direct way to know about their cardiovascular risks at a young age.

“A lot of clinical practice focuses around short-term risk,” Moran said. “There are recommendations to treat people with cholesterol medicines and blood pressure medicines based on their 10-year risk of [cardiac] events. That’s rational, but it’s also because most evidence comes from short-term studies—somewhat like only looking at the ground where the streetlight is shining.”

The message from this paper is: You know what? Making those changes later in your life will not reverse the unhealthy choices you made when you were younger. There’s no reason to wait. Andrew E. Moran

For their study, Zhang, Moran, and colleagues tracked blood pressure and LDL cholesterol levels among 36,030 people participating in six large, prospective, cohort studies conducted in the United States that collectively tracked exposures from young adulthood to later life. Cohorts derive from the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Risk Development in Young Adults (CARDIA) study, the Cardiovascular Health Study (CHS), the Framingham Heart Study Offspring Cohort, the Health, Aging, and Body Composition (Health ABC) study, and the Multi-Ethnic Study of Atherosclerosis (MESA). Median follow-up across cohorts was 17 years.

Of the six cohorts, only two—CARDIA and the Framingham Offspring Study—include LDL and BP levels for people from ages 18 to 39. To derive the risk of CHD and heart failure for individuals in the four cohorts in which risk factors were not directly measured, researchers leveraged the risk factors from CARDIA and Framingham to impute risk for the entire pooled study population.

Using an LDL level of less than 100 mg/dL as a reference point, researchers found that for young people with elevated LDL, the hazard ratio for developing CHD later in life was 1.62 (95% CI 1.25-2.10) at a level of 100 to 129 mg/dL; 1.89 (95% CI 1.43-2.50) at a level of 130 to 159 mg/dL; and 2.03 (95% CI 1.47-2.82) once levels crossed 160 mg/dL.

Having elevated systolic BP while young was associated with an increased relative risk of heart failure later on, a finding that became statistically significant at the highest readings. Using systolic BP of less than 120 mm Hg as a reference point, researchers found a significantly increased risk of heart failure with young adult systolic BPs ≥ 130 mm Hg (HR 1.37 (95% CI 1.17-1.61) for heart failure. Likewise, a young adult diastolic BP of ≥ 80 mm Hg was associated with a HR of 1.21 (95% CI 1.04-1.41) compared with a reading of < 80 mm Hg.

Of note, risk factor exposure—specifically elevated blood pressure—in later adulthood, but not at younger ages, was associated with an increased risk of stroke.

If you actually intervene at a younger age, you can actually regress the vessels to a healthier state and keep them there. Samuel S. Gidding

In an editorial accompanying the paper, Samuel S. Gidding, MD (Familial Hypercholesterolemia Foundation, Pasadena, CA), and Jennifer Robinson, MD (University of Iowa, Iowa City), argue that these findings strengthen the case for treating high cholesterol prior to the age of 40. If anything, Gidding and Robinson say, the analysis understates the current risks of high cholesterol at a young age. This is because today’s younger adults are more likely to be obese and to have diabetes than the cohorts at the time the studies were conducted.

“We and others have shown . . . that high cholesterol at a very young age predicts subclinical atherosclerosis. This [new research] extends that finding to actual events,” Gidding observed to TCTMD. “With atherosclerosis there’s a buildup over time and it’s less reversible as you get older. So if you actually intervene at a younger age, you can actually regress the vessels to a healthier state and keep them there.”