Cardiac Damage Starts Early When There’s Family History of Cardiometabolic Disease

Adolescents and young adults whose families have cardiometabolic disease are more likely than those without a family history to have left ventricular hypertrophy, with the prevalence growing fourfold between ages 17 and 24 years.

The results were recently published online in the European Journal of Preventive Cardiology.

Andrew O. Agbaje, MD (University of Eastern Finland, Kuopio), who co-authored the paper along with Douglas R. Corsi, MD (Rutgers University, New Brunswick, NJ), told TCTMD that LV hypertrophy serves as a useful marker for myocardial injury in pediatric populations, in which hard events like myocardial infarction and other clinical endpoints are rare.

While it’s known that offspring tend to follow in the footsteps of their parents with regard to cardiovascular disease, “we do not know when these discrepancies in the heart really start,” Agbaje explained. Even at a very young age, there may be “subtle changes in children that are apparently healthy . . . not knowing that something is already developing in the background without an obvious clinical presentation.”

To look at an earlier point in the trajectory, researchers turned to the England-based Avon Longitudinal Study of Parents and Children (ALSPAC). Unlike the Framingham Heart Study and other such projects, ALSPAC tracks parents from relatively early adulthood before events accrue and involves regular echocardiographic follow-up of offspring.

Agbaje said the proportion of adolescents with family histories of cardiometabolic disease in their study—three in 10—was surprisingly high. Moreover, those with this background have cardiac damage that progresses more quickly than their peers without a family history.

“We need to really change our ways of life, so we don’t set up the disease process in autopilot mode,” he stressed, adding that gaining muscle mass and doing even light physical activity—while avoiding long stretches of sedentary time—could go a long way toward better cardiometabolic health.

Clinicians, he advised, should take a holistic perspective and ask about family history even when caring for seemingly well young people. The cardiometabolic health of their parents provides “very important signals” about the environment the children are growing up in, said Agbaje.

More Rapid Rise in LV Hypertrophy

The study included 1,595 ALSPAC participants who had complete metabolic assessments and echocardiographic measures at 24 years. Nine hundred had cardiac measures at ages 17 and 24 years. A total of 1,350 participants had complete information on their family history of cardiometabolic disease as well as smoking and angiographic measures by age 24.

At baseline, mean age was 17.74 years and 30% had a family history of cardiometabolic disease, defined as hypertension, diabetes, hypercholesterolemia, or vascular disease in parents and siblings. Mean left ventricular mass indexed to height (LVMI) was 35.4 g/m²^.⁷.

At age 17, echo showed LV hypertrophy (LVMI ≥ 51 g/m²^.⁷) in 2.4% of the entire cohort and high LV filling pressure (E/e′ ≥ 8) in 0.7%. By age 24, these conditions were seen in 6.5% and 0.9%, respectively.

Youth with a positive family history of cardiometabolic disease had a fourfold rise in the prevalence of LV hypertrophy between ages 17 and 24. For those without this history, prevalence doubled. One case of LV hypertrophy would be expected to occur for every 60 adolescents whose parents and/or siblings had cardiometabolic disease.

While one in 60 may seem mild, the “rapidity of the progression” in prevalence is concerning, said Agbaje. “It quadruples within 7 years.”

After adjustment for sex, socioeconomic factors, and numerous time-varying covariates, having a family history of cardiometabolic disease increased the risks of LV hypertrophy (OR 1.20; 95% CI 1.09-1.32) and high LV filling pressure (OR 1.20; 95% CI 1.09-1.31), but not high relative wall thickness or LV diastolic function.

We need to really change our ways of life, so we don’t set up the disease process in autopilot mode. Andrew O. Agbaje

Glucose levels explained 9.5% of the increased risk of LV hypertrophy, but no other cardiometabolic or lifestyle factors were found to be statistically significant mediators. “Inherited susceptibility to metabolic dysfunction correlates with accelerated endothelial deterioration and pro-inflammatory atherogenic cascades, dysregulated lipid homeostasis, and hemodynamic perturbations that collectively precipitate chronic cardiovascular pathology,” the researchers explain.

They conclude: “Our findings provide supporting evidence to the European Society of Cardiology’s call to primordially prevent the risk of developing cardiovascular diseases in the young population through early intervention targeted at reducing the duration of long-term exposure to cardiometabolic risks across the lifespan.”

Agbaje said that more research to bolster prevention efforts in children is on the way. His latest study, recently presented at the American Heart Association 2025 Scientific Sessions, focuses on the best way to measure fat and muscle mass in the pediatric population. “It’s a missing gap. . . . Many things are superimposed from adult studies,” Agbaje commented.