ORLANDO, FL — Informing intermediate-risk patients of their probability of developing CHD over the next decade based on their genomic risk may encourage them to improve health outcomes, suggests new research.
The MI-GENES study, which included 203 patients, showed that those who received their genetic-risk score, based on 28 genetic variants, plus discussion about traditional CHD risk factors, had significantly lower levels of LDL-C 6 months later vs those who heard about traditional risk factors only (the primary end point, P=0.04).
Lead investigator Dr Iftikhar J Kullo (Mayo Clinic, Rochester, MN) told heartwire from Medscape that the LDL-C lowering most likely came from the group's greater initiation of statins. Kullo presented the results here at the American Heart Association (AHA) 2015 Scientific Sessions.
"This was a sort-of proof-of-concept study, and more research is needed," said Kullo. "However, as a clinician I've seen that heart attacks and sudden deaths occur without warning, and we haven't really gone beyond the Framinghams or the risk calculators. This is reaching toward the holy grail of cardiology: how to better estimate the risks so we can prevent these events."
Press briefing moderator Dr Donald Lloyd-Jones (Northwestern University Feinberg School of Medicine, Chicago, IL) noted that although integrating genetic information into clinical records and tests isn't yet widely available, "I think this is a very important step forward in precision medicine."
The participants (51% women; mean age 59.4 years) were randomly assigned to receive their 10-year probability of CHD based either on conventional risk factors alone (n=100; baseline LDL-C, 118.8 mg/dL) or with a genetic-risk score (n=103; LDL-C, 119.8 mg/dL).
Those in the latter group were also divided into subgroups based on high- or average/low-genetic-risk scores, which were delivered by a genetic counselor. All participants also met with a clinician "for shared decision making," reported Kullo. The CHD genetic-risk score was created from 28 genetic variants that did not include lipid or BP factors.
Between 24% and 30% of the participants had a family history of CHD, but "this was only modestly related to the patient's risk," said Kullo. The "mean tenure probability of adverse cardiac outcomes" in the overall group was 8.5, and the mean genetic-risk score was 1.1.
At the 6-month postdisclosure follow-up, the full group who received their genetic-risk scores had a mean LDL-C level of 96.5 mg/dL vs 105.9 mg/dL for those who didn't receive the scores. In addition, "the overall downward longitudinal trend" in LDL-C level was significantly greater in the former group vs the latter (P=0.04).
There were also significantly more users of statins in the genetic-risk–score group (39% vs 22%, respectively, P<0.01).
The subgroup with high genetic-risk scores had significantly lower LDL-C levels (92.3 mg/dL) than the conventional-risk-factor-only group (P =0.02), which stayed significant over the entire study period (P=0.007). However, there were no significant differences between the lower-genetic-risk–score subgroup (100.9 mg/dL) and the conventional risk group.
Secondary outcomes of physical activity, dietary fat intake, and anxiety levels did not differ significantly between the groups after risk disclosure.
The main take-away message is that "the genetic-risk information for coronary heart disease . . . can be effectively incorporated in the electronic health record and used at the point of care to guide drug therapy," said Kullo.
"We're moving toward a very personalized disease assessment," he added. "I'm not saying that genetics is the full answer; it's just one more thing. The more refined estimate you get, the better you will be able to target therapy. I would say you could also use imaging or biomarkers to come up with a more refined estimate."
Potential Game Changer
During the Q&A session after the press briefing, Kullo reiterated that genetic-risk profiles are not widely available. "We are in the process of developing this panel for clinical use. This was done at a Cleo-certified laboratory, and we were able to use it in the clinical setting."
He added that direct-to-consumer companies have marketed somewhat similar risk profiles, "but the FDA has clamped down because they weren't clearly convinced that the methods of using the genetic-risk estimates were appropriate or standard."
When moderator Lloyd-Jones asked whether receiving additional information with the word "genetic" in it may have been the contributing motivator for the genetic-risk–score group, Kullo said that was likely. "I think the higher estimated risk score stimulated the physician and patient to together make a decision about statin therapy."
Lloyd-Jones added that he would have liked to have seen that the risk scores motivated a lifestyle change in addition to a prescription change.
Overall, "this trial fits very nicely into the framework that was established in the 2013 risk assessment and cholesterol guidelines, where the first step should be a quantitative risk assessment using pooled cohort equations and then consideration of extra factors," such as family history, very high LDL-C, and possible evidence of subclinical atherosclerosis, he said.
"I think this genetic-risk score is most useful in those patients where we're on the fence or they're at 'intermediate risk' for lack of a better term," said Lloyd-Jones.
He added that a very, very low-risk patient is unlikely to be moved into a higher risk category based on a genetic-risk score. But for the intermediate-risk ones, "I think the addition of information can sometimes be a game changer. If it motivates the patient and I'm leaning toward treating them, I would love to take advantage of it."
Heartwire from Medscape © 2015
Cite this: MI-GENES: Discussing Genetic Risk for CHD May Motivate Patients to Lower LDL-C Levels - Medscape - Nov 19, 2015.