Certain CV Meds Tied to Higher MI Risk in Warmer Weather

Adults, no matter their age, are more vulnerable to experiencing an MI on hotter days if they’re taking beta-blockers or antiplatelet drugs, according to an observational study of German data. The same heat-associated risk was not seen among MI patients who had not been on the medications.

The study, published as a letter in Nature Cardiovascular Research, joins a growing body of literature that documents the link between high temperatures and CVD, as well as an upswing of interest in how climate change will affect heart health, with some suggesting it’s time for a subspecialty dedicated to climate cardiology.

Lead author Kai Chen, PhD (Yale School of Public Health, New Haven, CT), told TCTMD that their previous research has shown even short-term exposure to heat can trigger MIs and here they wanted to see whether common drugs aimed at CVD played a role in that risk. It’s especially relevant, he noted, given that “we’ve experienced this extreme heat almost globally during the past few weeks, from the UK to Europe, and now the US.”

Here, the puzzle they sought to solve, he said, is “whether the significantly increased risks for patients taking [antiplatelets and beta-blockers] are really due to the medications or if it’s simply because these patients are already very sick and that’s why they take a medication. It’s a very challenging question.”

One argument against this sort of confounding, said Chen, is that the study didn’t uncover similar links between heat and MI risk with calcium channel blockers, ACE inhibitors, or diuretics. Additionally, younger patients, who on average have less preexisting CHD, weren’t exempt from the added risk posed by antiplatelet agents and beta-blockers, and they had a more than threefold increase in risk with statin therapy during warmer weather.

It’s impossible for their study to tackle the exact mechanism, he acknowledged. But “what we know for sure is that these patients taking the medications, compared with [those not taking them], they are indeed more vulnerable. No matter what reason drives the increased risk, the conclusion we want to draw attention to is that patients taking these two medications should really watch out for themselves, especially during heat waves” by staying hydrated and seeking relief in cooling spaces, said Chen.

The message for patients, he stressed, is not to change their drug regimens.

Dhruv Kazi, MD (Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA), commenting on the results for TCTMD, also cautioned that any nonrandomized study is open to confounding.

Valuably, though, this is “one of the few studies that have systematically looked at younger adults” below age 60, whereas most of the studies conducted in the US have used Medicare data for older adults, he noted. Even taking the drugs out of the equation, with the idea that they’re markers, “it’s plausible that young adults with established cardiovascular disease are probably at increased risk from heat-related events” in comparison to their same-age peers without CVD, said Kazi.

He, too, stressed that clinicians shouldn’t take patients off their medications when the temperature goes up.

Higher Risk, but Questions, Too

For their study, Chen and colleagues used the MONICA/KORA MI registry to identify 2,494 patients who had a nonfatal MI in Augsburg, Germany, during warm-weather months (May-September) between 2001 and 2014. Most were aged 60-74 years, and three-quarters were men. Weather data were collected from local monitoring stations.

Before their MI, 32% of the individuals were taking antiplatelet agents and 37.2% used beta-blockers. Rates of ACE inhibitor, calcium channel blocker, diuretic, and statin use were 25.2%, 15.9%, 23.4%, and 23.6%, respectively.

The researchers used a case-control design, wherein each MI case served as its own control. To do so, they compared mean temperatures on the day the MI occurred against the same day of the week within the same month (eg, second Monday of May versus other Mondays in May). Risk on hotter days was compared to risk at a daily mean temperature of 45.5 °F (7.5 °C), when their calculations had shown MIs to be least likely.

On days when mean temperatures reached 75.6 °F (24.2 °C)—the 95th percentile—people taking antiplatelets were more likely to experience an MI (OR 1.63; 95% CI 1.07-2.46) than on the least-risky days. Beta-blockers also raised the MI risk (OR 1.65; 95% CI 1.11-2.45). Patients on both medications saw an even greater increase (OR 1.75; 95% CI 1.12-2.73), whereas those on neither saw no difference in MI risk between warmer versus colder days.

No significant relationships between temperature and MI were seen for ACE inhibitors, calcium channel blockers, or diuretics, though there was a trend seen in relation to statin use.

The authors acknowledge the potential for confounders. For example, it could be that patients already at higher risk for experiencing MI were more apt to be on antiplatelets and beta-blockers in the first place. Indeed, the heat-related MI risk was seen among patients with preexisting coronary heart disease (OR 2.17; 95% CI 1.40-3.38), fully 84.5% of whom were taking the medications, but not those without the disease.

Yet, they add, “an argument against confounding by indication” is that younger patients (ages 25-59) saw a stronger link between these two drugs and MI risk than did older patients (60-74), despite the younger group having a lower prevalence of coronary heart disease.

Interestingly, for the younger patients, statin use was associated with triple the risk of MI on warmer versus colder days (OR 3.39; 95% CI 1.84-6.25). The same link wasn’t seen among patients aged 60 to 74 years.

Kazi pointed out that no one who takes statins or antiplatelet agents does so casually, but for a reason. “Especially in younger adults, these are often markers of underlying pathology,” he observed.

For beta-blockers, though, Kazi said there’s a more convincing link.

“It is plausible that beta-blockers actually modify risk, though I wouldn’t hang my hat on that based on this one study,” he commented, adding that other reports have made the case that the body’s temperature regulation and homeostasis are altered when patients are on a beta-blocker. “Whether that affects our ability to respond to heat or ability to compensate for the stress resulting from heat is unclear. You can’t tell that from this study alone, but there’s a signal there that says we should probably think about how beta-blockers affect our cardiovascular risk.”

Also worth remembering, Kazi said, is that temperatures don’t have to reach as high as one might think—into the 90s or 100s—to have cardiovascular effects on a population level. The impact of heat is less severe in places that typically have hot weather and more severe in places where people aren’t accustomed to higher temperatures or don’t have the resources, like air conditioning, to deal with them.

Chen said that, going forward, additional studies are required to see if their findings can be replicated in other population settings and larger data sets. This may help “disentangle whether it is indeed these medications, or it’s more the indication, or both,” he added.

“Our findings, if confirmed, can help clinicians, patients, and public health officials develop targeted strategies to reduce the burden of cardiovascular disease under climate change,” the investigators conclude.