Longer exposure to CV risk factors foretells CVD

Intervene early. Cumulative exposure to common cardiovascular (CV) risk factors could be a harbinger of cardiovascular disease (CVD) in future.

This is the takeaway from the CARDIA study.

Ultimately, the duration and intensity of exposure to LDL-cholesterol, HDL-cholesterol, triglycerides, mean arterial pressure, and pulse pressure over the years cumulatively impact how likely an individual develops coronary heart disease (CHD), stroke, or congestive heart failure (CHF) after age 40, according to the investigators.

Additionally, understanding an individual’s lifetime risk may be the key to early prevention strategies.

CARDIA in their minds

Researchers tracked for 30 years asymptomatic men and women  (n=4,958) aged 18–30 years enrolled in the CARDIA study between 1985 and 1986. Incident CVD rates were calculated as a function of the time-varying course of independent risk factors (LDL-C, HDL-C, triglycerides, mean arterial pressure, and pulse pressure) operating simultaneously.

 “The resulting quantitative relationship between risk factors and CVD informs the formulation of tailored CVD mitigation strategies, design of primary prevention trials, and assessment of the likely impact of risk factor-based interventions on public health,” said lead author Dr Michael Domanski from the University of Maryland School of Medicine, Baltimore, US.

 Longer exposure suggests more CVD

The median follow-up duration of the study was 19 years after age 40, during which 316 individuals had a first CV event. There were 166 cases of nonfatal CHD, 108 strokes, and 81 CHF.

“The intensity and length of exposure to the CV risk factors, expressed as area under the curve, were strongly, positively, and independently associated with incident CVD risk after age 40,” Domanski reported.

Patients in quartile 4 of LDL-C exposure level and duration had a 12.6 percent CVD event rate at age 60 vs 4.3 percent, 5.7 percent, and 8.4 percent in quartiles 1 through 3, respectively. There was a trend toward fewer CVD with greater cumulative exposure to HDL-C.

Event rates based on exposure to triglyceride level and duration ranged from 3.3 percent in quartile 1 to 12.6 percent in quartile 4. Similar patterns were observed for mean arterial and pulse pressure.

When individual components of incident CVD were analysed, LDL-C exposure significantly predicted CHD, but not CHF or stroke. Mean arterial pressure was significantly linked to all three endpoints, but only marginally for CHD.

Being Black increased the risk of incident CVD, CHF, and stroke. “This suggests that being Black is a phenotypic marker for unexplained significant racial differences in CVD susceptibility,” said the researchers.  Interestingly, male sex was tied to CHF.

The study builds on a previous study by Domanski’s team showing that increased lifetime exposure to high LDL-C predicts ASCVD. [J Am Coll Cardiol 2020;76:1517-1520]

Moving forward

In an accompanying editorial, Dr Hector Ventura and two other experts from John Ochsner Heart and Vascular Institute, New Orleans, Los Angeles, US said the study changes how clinicians view and set about primary prevention strategies going forward. [J Am Coll Cardiol 2023; 81:1162–1164]

“We need to prevent and treat elevated triglycerides … reduce intake of simple sugars, carbohydrates, and alcohol. We need to control weight gain and eventual overweight/obesity, increase levels of physical activity, and exercise long before age 40.”

Lowering LDL-C by reducing the high intake of cholesterol and saturated fats by adopting a Mediterranean-style diet should also begin early in life. “This is to reduce the progression of atherosclerosis and CHD,” he pointed out. “Lowering of blood pressure should also start early, so with sodium and alcohol intake. Potassium and calcium intake should be increased, with the goal of maintaining a healthy body weight.”

Changing practice

“The usual method is to calculate the risk through risk factors measured at one point in time. Even in clinical practice, we keep working on risk factors measured on a specific day,” commented Dr Jean-Philippe Empana from the Université Paris Cité, INSERM, Paris, France. “But I think we should really move towards looking at cumulative exposure instead as it brings new findings, new meaning, and new predictions.”

Patients’ risk factor measurements should be recorded not only once, but repeatedly, by their cardiologist or GP. “There is a need to educate physicians because it takes 10 years from one discovery down to its implementation in the field,” he said with conviction.