Troponin Trajectories Differ Over the Years for Men, Women

Cardiac troponin concentrations follow a different arc across the years in women versus men, according to a new study tracking how biomarker values shifted by sex over 15 years.

Unlike the more-familiar concept of serial troponins, where testing is done in quick succession over just a few hours to triage patients with acute chest pain and where sex discrepancies are a known issue, here researchers took a longer-term view in participants who first enrolled in the longitudinal Whitehall II study back in the 1980s.

Senior author Dorien M. Kimenai, PhD (University of Edinburgh, Scotland), told TCTMD the current work follows their 2021 paper that found sex differences in troponin when assessed at a single time point. This paper, recently published in Circulation, is “the first study that’s now made insights into the trajectories for women and men.”

That there were differences in cardiac troponin concentrations between women and men does not come as a surprise, said Kimenai. What was novel, she noted, is that “we saw that the concentrations were lagging a decade behind [for women] and also that the trajectory is slightly steeper for women than men.”

Kimenai pointed out that with the advent of high-sensitivity assays, it’s now possible to detect such low levels of troponin that the biomarker can be measured more accurately even in “presumably healthy individuals,” thus raising the question of whether the troponin results might be applied outside of the acute setting, perhaps serving as a tool to refine risk stratification in primary prevention.

Troponin Climbs More Steeply in Women

Lead author Marie de Bakker, MSc (University Medical Center Rotterdam, the Netherlands), Kimenai, and colleagues turned to the Whitehall II cohort, in which high-sensitivity cardiac troponin I (hs-cTnI) was measured as many as three times over 15 years using the Siemens Atellica IM High-Sensitivity Troponin I assay (Siemens Healthineers). Testing was conducted during three time periods: 1997 to 1999, 2007 to 2009, and 2012 to 2013.

A total of 7,293 people, 29.4% female, underwent the initial testing, of whom around 7% had known CVD. Mean age was 57 for women and 58 for men. Median hs-cTnI at baseline was lower in women (2.4 vs 3.7 ng/L in men; P < 0.001).

Of the original group, 75.6% of women and 81.5% had a second measurement, while 50.9% of women and 57.4% of men had a third. Women continued to have lower hs-cTnI values than men across the years, though their trajectories rose more sharply, especially after age 46.

On average, “women reached equivalent cardiac troponin concentrations approximately a decade after men. For example, a cardiac troponin concentration of 5 ng/L, corresponds with an average age of 73 years and 62 years in women and men, respectively,” the researchers report, adding that no inflection was seen in pace of change before versus after menopause.

Multivariable analyses found age, diabetes, systolic blood pressure, total cholesterol, and HDL were significantly associated with higher hs-cTnI in both women and men. Yet there were some differences in predictors: body mass index (BMI) was more tightly tied to increased troponin in men versus women, while diabetes was associated with increased troponin in women but lower troponin in men.

Over a median follow-up of 20.9 years, higher hs-cTnI values were linked to a greater risk of developing the primary outcome (nonfatal MI, nonfatal stroke, or CV death) for both female and male study participants (adjusted HRs per twofold difference of 1.34 and 1.30, respectively).

“Finally, the temporal pattern of cardiac troponin was more strongly related to cardiovascular events in women than men, although the association was attenuated after adjustment for cardiovascular risk factors,” the investigators write. “Our findings highlight the need for sex-specific approaches when cardiac troponin testing is applied in cardiovascular risk prediction.”

Dynamic, Not Static

It’s now time to explore what factors, like diabetes and BMI, might be influencing the divide. “I think we also have to acknowledge with these observational data we cannot really go into the mechanisms,” Kimenai said.

She stressed that more research is needed before their findings on serial troponin can be applied clinically in primary prevention. But based on their findings, it seems that incorporating troponin as a continuous measure—not specific thresholds—in risk-estimation systems is the way to go. With thresholds, “I think by default you’re going to disadvantage some important subgroups” related to age and sex, she noted.

Another novelty, said Kimenai, is that their study raises the possibility of a more-dynamic approach to gauging risk: multistate joint modeling. “The principle is basically that we are using all the measurements that are available” to characterize a person’s risk, she explained. “The advantage to that is you not only measure at one moment in time but you also can incorporate the change of a risk factor over time, which may provide additional prognostic information.”

The next step is to look at other factors, not just troponin, that are currently used in snapshot-like risk calculators such as SCORE2 and the Pooled Cohort Equations, said Kimenai. The dynamic approach to estimating risk, if it pans out in future studies, also potentially could be applied across multiple disease states, not just cardiovascular, she added.