CLINICAL
NEWS
pecially weight loss.10 Doing so produces benefits
relating to AF prevention, better AF management,
and a reduction in AF complications, including
stroke.
Gregg C. Fonarow, MD, is co-chief of the division of cardiology at the University of California,
Los Angeles, and director the Ahmanson–UCLA
Cardiomyopathy Center. He goes further than
Miller et al.: for all the issues
we’ve been discussing, the top
three recommendations he
gives to cardiologists are help
prevent obesity, help prevent
obesity, and help prevent
obesity.
To lis ten to an
Based on his own work,
interview with Gregg
it is also best if you identify
C. Fonarow, MD, on
obesity and HF, scan
overweight and obesity, meathe code.
suring both weight and waist
circumference. Assess risk
factors present in all patients
and initiate proven cardioprotective therapies. For patients
with obesity and patients
with diabetes, that would include angiotensin-converting
enzyme inhibitors or angiotensin receptor blockers, statin therapy, blood pressure control, and
sodium-glucose co-transporter 2 inhibitors, a class
of prescription medicines that are approved by the
U.S. Food and Drug Administration for use with
diet and exercise to lower blood glucose in adults
with type 2 diabetes.
Clinicians should recommend regular moderate exercise to patients with AF, not only to reduce
AF, but also for its overall cardiovascular benefits.
Overall, the evidence suggests that intentional
weight loss improves outcomes in patients with
ischemic heart disease, diabetes, and AF. While
losing weight improves quality of life in HF patients, Dr. Fonarow said more studies are necessary to determine whether intentional weight loss
will improve outcomes in patients with HF. ■
REFERENCES:
1. Kenchaiah S, Evans JC, Levy D, et al. N Engl J Med.
2002;347:305-13.
2. Fonarow GC, Srikanthan P, Costanzo MR, Cintron GB,
Lopatin M; ADHERE Scientific Advisory Committee and
Investigators. Am Heart J. 2007;153:74-81.
3. Clark AL, Fonarow GC, Horwich TB. J Card Fail.
2011;17:374-80.
4. Clark AL, Chyu J, Horwich TB. Am J Cardiol.
2012;110:77-82.
5. Lavie CJ, McAuley PA, Church TS, Milani RV, Blair SN.
J Am Coll Cardiol. 2014;63:1345-54.
6. Barry VW, Baruth M, Beets MW, Durstine JL, Liu J, Blair
SN. Prog Cardiovasc Dis. 2014;56:382-90.
7. Kannel WB, McGee DL. JAMA. 1979;241:2035-8.
8. Horwich TB, Fonarow GC. J Am Coll Cardiol.
2010;55:283-93.
9. Magnani JW, Hylek EM, Apovian CM. Circulation.
2013;128:401-5.
10. Miller JD, Aronis KN, Chrispin J, et al. J Am Coll Cardiol.
2015;66:2899-906.
24
CardioSource WorldNews
American College of Cardiology Extended Learning
MI-GENES: Do Patients Want to Know their
Genetic Risk?
(Does it Matter?)
D
o you want to know? For that matter, do
your patients want to know?
To reduce risk of acute coronary syndromes, the benefits of a healthy lifestyle are clear,
but genetics can still stack the deck. The question
is: what happens if you turn the cards over and see
your genetic specifics?
We’re learning more and more about what could
be in the cards. Through DNA genotyping, investigators recently tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868
patients with coronary artery disease (CAD) and
120,770 controls without CAD. They found that some
genetic variants or SNPS (single nucleotide polymorphisms; pronounced “snips”) offer a natural advantage in protecting against heart disease while others
portend a distinct disadvantage.
There are 46 SNPS that have been associated
with susceptibility to CAD. They searched genetic
variants that altered proteins to identify those that
appeared to influence heart disease risk,
as errors in proteins can have major
physiological consequences.
For the study, published in the New
England Journal of Medicine, researchIftikhar J. Kullo,
ers – including Iftikhar J. Kullo, MD,
MD
of the Mayo Clinic – identified genes
already shown to confer an advantage or a vulnerability in protecting against heart disease risk.1
Two new ones stood out: ANGPTL4 and SVEP1.
Rare errors in ANGPTL4 were associated with
reduced risk of CAD. The reduction varied from
14% for a small error in the gene to cutting risk by
about 50% when an entire copy of the gene was
disabled. Carriers of ANGPTL4 loss-of-function
alleles had triglyceride levels that were 35% lower
than those seen in people who did not carry a
loss-of-function allele (p = 0.003).
The other gene, SVEP1, showed the opposite
correlation: a rare error increased CAD risk by
about 14%. While ANGPTL4 has been the subject
of much study, SVEP1 is a bit of a mystery. An error in SVEP1 was linked to higher blood pressure
in their study populations, but beyond that there
are few clues to what it’s doing.
So, it might be good to know what an individual’s specific genes suggest in terms of added
—or lesser—risk. You would think such knowledge
would be valuable and inspire healthy lifestyle
changes. Yeah, well, maybe not. A new study offers
some insight into just how ingrained our habits
and lifestyle actually are: investigators found no
evidence that genetic tests change unhealthy habits.
A team of British researchers reviewed the
results of 18 studies that looked at whether communicating DNA test results for conditions such as
cancer and heart disease led people to make healthy
changes.2 They found nothing to suggest that
people adopted healthier behaviors, such as quitting
smoking or eating more healthfully, after receiving
their DNA results.
While individuals were not motivated to make
healthy changes, at least there was no indication
that knowledge of their genetic risk discouraged such
changes. In other words, no inclination to look at
troubling results and say, “My gene pool is a cesspool;
I might as well drink and smoke more. Why not?”
THE MI-GENES CLINICAL TRIAL
Does genetic risk at least factor into shared decision
making when both physician and patient know the
genetics score? Kullo and colleagues also conducted
the MI-GENES (Myocardial Infarction Genes) study,
looking at the value of incorporating a genetic risk
score (GRS) in coronary heart disease (CHD) risk
estimates to see whether the additional knowledge
led individuals to lower their low-density lipoprotein cholesterol (LDL-C) levels.3
MI-GENES investigators enlisted 203 participants
(45-65 years of age) at intermediate risk for CHD and
not on statin therapy. They were randomly assigned
to receive a standard 10-year probability of CHD risk
score with or without the additional information from
a GRS. Risk was disclosed by a genetic counselor, and
then participants were stratified as having high or
average/low GRS, followed b y shared decision making
regarding statin therapy with a physician.
At 6 months, the group who received both a
standard risk score and a GRS had a lower LDL-C
than the conventional 10-year CHD calculation alone
(96.5 ± 32.7 vs. 105.9 ± 33.3 mg/dl; p = 0.04). Participants with a high genetics risk score had lower
LDL-C levels (p = 0.02) compared to a standard
10-year risk estimation alone, but not significantly
different from those who had an average/low GRS
(p = 0.18). Statins were initiated more often in the
individuals who got the results of their GRS (39% vs.
22% with the standard risk score alone; p < 0.01).
Granted, these were modest changes in LDL-C and
disclosure of a GRS did not lead to significant differences in dietary fat intake, physical activity, or anxiety
levels. Still, here is one study suggesting that genetic risk
information for CHD can be used at the point of care to
enable shared decision making regarding statin therapy,
leading to a subsequent change in LDL-C levels. ■
REFERENCES:
1. Myocardial Infarction Genetics and CARDIoGRAM Exome
Consortia Investigators. N Engl J Med. 2016;374:1134-44.
2. Hollands GJ, French DP, Griffin SJ, et al. BMJ.
2016;352:i1102.
3. Kullo IJ, Jouni H, Austin EE, et al. Circulation.
2016;133:1181-8.
September 2016