Risk Factors Present in Nearly All Patients Who Develop CVD

Virtually every patient who develops cardiovascular disease has at least one traditional risk factor that is not at ideal levels, according to a new analysis.

Suboptimal blood pressure was the most common risk factor among those who went on to develop cardiovascular disease, including MI, heart failure (HF), coronary heart disease (CHD), and stroke, while elevated cholesterol was the second most prevalent risk factor.

“Importantly, these risk factors rarely existed alone, and 93% to 97% of patients had a combination of two or more risk factors before experiencing cardiovascular disease events,” lead investigator Hokyou Lee, MD, PhD (Yonsei University College of Medicine, Seoul, Republic of Korea), told TCTMD.

In the past several years, there have been reports that many patients who develop ischemic heart disease don’t have standard modifiable risk factors, often referred to as SMuRFs. In one Australian study, for example, the proportion of STEMI patients without SMuRFs increased from 11% to 27% between 2006 and 2014 and those without modifiable risk factors fared worse in follow-up than those with conventional risk factors.

“Several recent studies claimed that coronary heart disease can often develop without traditional risk factors like high blood pressure, high cholesterol, diabetes, or smoking,” Lee told TCTMD via email. “But when we looked closely, we realized those reports might actually reflect missed risk factor diagnoses or risk factor levels that were nonoptimal in terms of cardiovascular risk, since many of these risk factors have a continuous rather than a yes-or-no relationship with risk of developing CVD.”

Nathan Wong, PhD (UC Irvine, CA), who directs the heart disease prevention program at his institute, said that one of the problems with the current approach to counseling and treatment is that physicians are not advising or intervening until risk factors are clinically elevated. It’s often not until patients have diabetes, hypertension, or hypercholesterolemia that there is a focus on treatment.

“By then you’re so far out of the optimal range that the horse is out of the barn, so to speak,” Wong told TCTMD. “The problem is that we practice reactive medicine rather than preventive medicine.”

It’s easy for patients to creep above “optimal” thresholds of 120/80 mm Hg without guidance on lifestyle changes to “re-optimize” their blood pressure, said Wong. Cardiovascular disease is often asymptomatic and subclinical for many years, “brewing with suboptimal risk factors that are not yet clinically diagnosed” and addressed, said Wong. 

Suboptimal Risk Factors

The new study, which was published in JACC, aimed to determine prior control of traditional risk factors at optimal levels—blood pressure, cholesterol, and glucose levels, as well as smoking status—before a first cardiovascular disease event. Researchers focused on two population-based cohorts: 9.3 million adults 20 years and older in the Korean National Health Insurance Service (KNHIS) and 6,803 adults 45 to 84 years old in Multi-Ethnic Study of Atherosclerosis (MESA).

Over median follow-ups of 13.3 and 17.7 years, respectively, there were 601,025 and 1,188 cardiovascular events in the KNHIS and MESA cohorts. In KNHIS, the median age was 60.5 years at first examination and 68.5 years at the time of the event, while in MESA, the respective median ages were 67.2 and 76.1 years. In KNHIS and MESA, 40.6% and 43.9% of patients were women.

Prior to the first cardiovascular event (MI, heart failure, stroke, or death from CVD), 99.3% and 99.5% of the KNHIS and MESA cohorts had at least one nonoptimized risk factor, with more than 94% having elevated blood pressure (defined as systolic ≥ 120 or diastolic ≥ 80 mm Hg or use of antihypertensive medication). Roughly 77% and 72% of those enrolled in KNHIS and MESA had elevated total cholesterol levels (≥ 200 mg/dL or use of a lipid-lowering treatment) prior to the cardiovascular disease event. Glucose control was slightly better in MESA, but the American cohort had more past/current smokers than those in KNHIS who developed cardiovascular disease.

The problem is that we practice reactive medicine rather than preventive medicine. Nathan Wong

“Surprisingly, the results were almost identical between the Korean and US cohorts in that traditional risk factors were universally present before CVD events in both cohorts,” said Lee. “That consistency across very different populations and health systems makes our findings especially strong and shows the value of international collaboration.”

Before any CHD, MI, heart failure, or stroke event, results were consistent. Prior to each of these outcomes, more than 99% of patients in the two cohorts had at least one nonoptimally controlled risk factor. Before HF occurred, for example, roughly 96% of patients had nonoptimal blood pressures and more than 70% (70.7% in MESA and 78.7% in KNHIS) had elevated cholesterol levels.

Lee said cardiologists may see patients with an MI or significant coronary heart disease without apparent risk factors, but that their research suggests they are present, likely either undiagnosed or at levels just below usual clinical thresholds.

“For patients, this means that checking blood pressure, cholesterol, and blood sugar at every medical visit is critical,” he said. “Keeping these risk factors at truly healthy levels and avoiding nicotine exposure, as outlined in the American Heart Association’s ‘Life’s Essential 8‘ remains the most effective way to prevent heart disease and stroke.”

Shift Towards Primordial Prevention

Jeffrey Berger, MD (NYU Langone Health, New York, NY), another preventive cardiologist, said he’s been told by people that they hope to never run into him in his professional setting.

“They say, ‘Oh, it’s nice to meet you. You’re a cardiologist. I hope I never have to see you,’” Berger told TCTMD. “I tell them I’m a prevention-focused cardiologist and I think you should hope to see me. There is so much we can do to delay or prevent disease if we start early enough.”

Primordial prevention—making lifestyle changes before the onset of cardiovascular risk factors—is critical, said Berger. “Patients, or community-dwelling folks, think many times that they’ll see a doctor when they’re sick,” he said. “I think this study should really get them to rethink that strategy. You should be seeing them throughout one’s life.”

I tell them I’m a prevention-focused cardiologist and I think you should hope to see me. Jeffrey Berger

Berger noted that patients in MESA and KNHIS who didn’t develop cardiovascular disease also had very poor optimization of risk factors. “What that means is that this is not great for the prediction of who is likely to have an event, but it definitely reinforces the concept that people should be paying attention to their risk factors,” he said.  

Even among patients with high risk for cardiovascular disease based on a polygenic risk score, following a healthy lifestyle is associated with more than a 50% lower risk of future coronary heart disease, said Wong.

“A strong family history should motivate you to do even more, but we can definitely mitigate a reasonable portion of genetic risk [with] a healthy lifestyle,” he said.

Berger added that prevention remains an uphill battle, with the healthcare system geared toward caring for the sick. “At the system level, we’re really playing catch-up,” he said. “For so long, we’ve been dealing with fixing acute problems when they come up. Issues related to prevention aren’t given enough attention.”