Knowing Genetic Risk for MI Motivates Patients, Physicians to Get Cholesterol Levels Lower

ORLANDO, FL—Genetic screening of MI risk factors could increase the likelihood that patients at intermediate-risk receive statin therapy and actually achieve lower cholesterol levels, particularly if the genetic results are shared with patients, a new study shows.

Knowing Genetic Risk for MI Motivates Patients, Physicians to Get Cholesterol Levels Lower

For the MI-GENES study, researchers led by Iftikhar J. Kullo, MD, of the Mayo Clinic (Rochester, MN), randomized 203 intermediate-risk patients (mean age 59.4 years; 47.8% men)—from a single county and not on statins—to receive their 10-year risk of coronary heart disease base on the Framingham Risk Score with or without results of a genetic risk score derived from 23 genetic variants.

After 6 months of receiving their respective analyses, patients who were given the additional genetic information had lower LDL cholesterol levels (96.5 mg/dL) than those who only knew their conventional risk scores (105.9 mg/dL; P = .04). Specifically, those identified as high risk by genetic examination had lower LDL levels than the entirety of the conventional score group (92.3 mg/dL; P = .02), but this was not the case for those with low-to-average genetic scores (100.9 mg/dL; P = .18). Overall, there was a greater longitudinal downward trend in LDL cholesterol for the genetic vs conventional risk factor groups (P = .04).

With regard to pharmacotherapy, those in the genetic screening group were more likely to receive any statins than patients in the conventional score group over the entire study period regardless of identified risk (39% vs 22%; P < .01).

Investigators did not observe any differences in dietary fat intake, physical activity, or anxiety levels between the cohorts throughout the study.

More Information for EHRs

 “Our study exemplifies precision medicine and motivates further investigation of the clinical utility of genetic risk assessment for prevention of [coronary heart disease],” Kullo concluded, adding that this information could be “effectively incorporated” into a patient’s electronic health record to be easily accessed as a reference for guiding therapy going forward.

However, given the fact that this study only looked at patients from a single county in Minnesota, he acknowledges that future studies should randomize patients from a wider range of ethnic backgrounds.

In a press briefing, Kullo said this kind of genetic screening is not widely available to the public. “We are in the process of developing this panel for clinical use,” he noted. “I should mention that this was done in a CLIA-certified laboratory and we were able to use it in the clinical setting.”

Donald Lloyd-Jones, MD, of Northwestern University (Chicago, IL), questioned whether it was the actual genetic risk score that motivated the LDL decrease in patients who received it or if it was “just the fact that they were getting additional information that had the word genetic in it.”

Kullo replied that adding genetic results to the information patients with higher baseline risk are already receiving led “to an estimated [even] higher risk that stimulated the physician and patient to together make the decision about statin therapy.” Conversely, he said, a low genetic risk score would be unlikely to “downgrade” the risk already estimated from conventional methods.

Unfortunately, Jones said, the added genetic information “didn’t make it all the way to motivating lifestyle change.”

Optimizing Risk Stratification

“The challenge in preventative cardiology is how to better risk stratify intermediate risk individuals, as those would be individuals who would the benefit the most,” Kullo said. Importantly, he noted, family history and genetic risk score are “somewhat independent” so one cannot be substituted for the other.

“We are projecting to a future where genome sequencing will be available to most individuals. In this case, this information would be ‘free,’” so cost will not be as much of an issue, he continued.

Moreover, Lloyd-Jones said MI-GENES “fits nicely into the framework of what was established [in the] 2013 risk assessment and cholesterol guidelines…. If additional information is available, such as this genetic risk score, that does provide additional or orthogonal information, I think it’s most useful in patients [for whom] we’re on the fence.

“If a patient is at very low risk, it’s unlikely this genetic risk score or much else would move them into higher risk category,” he added. “Likewise, if they are very high risk, as a clinician I’d be reluctant to withhold therapy from that individual unless I had very good evidence that they really were atherosclerosis free. In that middle group, that additional information can sometimes be a game changer…. If I'm leaning towards treating them and this makes [the patient] more likely to [take their medications], I’d love to take advantage of that.”

Kullo IJ. The effect of disclosing genomic risk of coronary heart disease on LDL cholesterol levels: the Myocardial Infarction Genes (MI-GENES) study. Presented at: American Heart Association Scientific Sessions; November 9, 2015; Orlando, FL.

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  • Kullo and Lloyd-Jones report no relevant conflicts of interest.