EXPERT ANALYSIS FROM THE ANNUAL CARDIOVASCULAR CONFERENCE AT SNOWMASS
SNOWMASS, COLO. (FRONTLINE MEDICAL NEWS) – More than 960,000 new cases of heart failure will occur in the United States this year – and most of them could have been prevented, Gregg C. Fonarow, MD, asserted at the Annual Cardiovascular Conference at Snowmass.
Preventing heart failure doesn’t require heroic measures. It entails identifying high-risk individuals while they are still asymptomatic and free of structural heart disease – that is, patients who are stage A, pre–heart failure, in the American College of Cardiology/American Heart Association classification system for heart failure – and then addressing their modifiable risk factors via evidence-based, guideline-directed medical therapy, said Dr. Fonarow , professor of cardiovascular medicine and cochief of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.
The two top risk factors for the development of heart failure are hypertension and ischemic heart disease. Close to 80% of patients presenting with heart failure have antecedent hypertension, and a history of ischemic heart disease is nearly as common. Other major risk factors include obesity, diabetes, smoking, dyslipidemia, metabolic syndrome, and renal insufficiency.
A special word about obesity: A Framingham Heart Study analysis concluded that, after controlling for other cardiovascular risk factors, obese individuals had double the risk of new-onset heart failure, compared with normal weight subjects, during a mean follow-up of 14 years. For each one-unit increase in body mass index, the adjusted risk of heart failure climbed by 5% in men and 7% in women ( N Engl J Med. 2002 Aug 1;347[5]:305-13 ). And that spells trouble down the line.
“You can imagine, with the marked increase in overweight and obesity status now affecting over half of U.S. adults, what this will mean for a potential rise in heart failure prevalence and incidence unless we do something further to modify this,” the cardiologist observed.
Dr. Fonarow is a member of the writing group for the ACC/AHA guidelines on management of heart failure. They recommend as a risk reduction strategy identification of patients with stage A pre–heart failure and addressing their risk factors: treating their hypertension and lipid disorders, gaining control over metabolic syndrome, discouraging heavy alcohol intake, and encouraging smoking cessation and regular exercise ( J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239 ).
What kind of reduction in heart failure risk can be expected via these measures?
Antihypertensive therapy
More than a quarter century ago, the landmark SHEP trial (Systolic Hypertension in the Elderly Program) in more than 4,700 hypertensive seniors showed that treatment with diuretics and beta-blockers resulted in a 49% reduction in heart failure events, compared with placebo. And this has been a consistent finding in other studies: A meta-analysis of all 12 major randomized trials of antihypertensive therapy conducted over a 20-year period showed that treatment resulted in a whopping 52% reduction in the risk of heart failure ( J Am Coll Cardiol. 1995 Apr; 27[5]:1214-8 ).
“If you ask most people why they’re on antihypertensive medication, they say, ‘Oh, to prevent heart attacks and stroke.’ But in fact the greatest relative risk reduction that we see is this remarkable reduction in the risk of developing heart failure with blood pressure treatment,” Dr. Fonarow said.
There has been some argument within medicine as to whether aggressive blood pressure lowering is appropriate in individuals over age 80. But in the HYVET trial (Hypertension in the Very Elderly Trial) conducted in that age group, the use of diuretics and/or ACE inhibitors to lower systolic blood pressure from roughly 155 mm Hg to 145 mm Hg resulted in a dramatic 64% reduction in the rate of new-onset heart failure ( N Engl J Med. 2008 May 1;358[18]:1887-98 ).
How low to go with blood pressure reduction in order to maximize the heart failure risk reduction benefit? In the SPRINT trial (Systolic Blood Pressure Intervention Trial) of 9,361 hypertensive patients with a history of cardiovascular disease or multiple risk factors, participants randomized to a goal of less than 120 mm Hg enjoyed a 38% lower risk of heart failure events, compared with those whose target was less than 140 mm Hg ( N Engl J Med. 2015 Nov 26;373[22]:2103-16 ).
A secondary analysis from SPRINT showed that the risk of acute decompensated heart failure was 37% lower in patients treated to the target of less than 120 mm Hg. That finding takes on particular importance because SPRINT participants who developed acute decompensated heart failure had a 27-fold increase in cardiovascular death (Circ Heart Fail. 2017 Apr; doi: 10.1161/CIRCHEARTFAILURE.116.003613 ).
Lipid lowering
A meta-analysis of four major, randomized clinical trials of intensive versus moderate statin therapy in 27,546 patients with stable coronary artery disease or acute coronary syndrome concluded that intensive therapy resulted in a 27% reduction in the risk of hospitalization for heart failure ( J Am Coll Cardiol. 2006 Jun 6;47[11]:2326-31 ).
SGLT-2 inhibition
Until the randomized EMPA-REG OUTCOME trial of the sodium-glucose transporter 2 (SGLT-2) inhibitor empagliflozin(Jardiance), no glucose-lowering drug available for treatment of type 2 diabetes had shown any benefit in terms of reducing diabetic patients’ elevated risk of heart failure. Neither had weight loss. Abundant evidence showed that glycemic control had no impact on the risk of heart failure events. So EMPA-REG OUTCOME was cause for celebration among heart failure specialists, with its demonstration of a 35% reduction in the risk of hospitalization for heart failure, compared with placebo in more than 7,000 randomized patients. The risk of death because of heart failure was chopped by 68%. Sharp reductions in other cardiovascular events were also seen with empagliflozin ( N Engl J Med. 2015 Nov 26;373[22]:2117-28 ).
Similar benefits were subsequently documented with another SGLT-2 inhibitor, canagliflozin(Invokana), in the CANVAS study program ( N Engl J Med. 2017 Aug 17;377:644-57 ).
The reduction in cardiovascular mortality achieved with empagliflozin in EMPA-REG OUTCOME was actually bigger than seen with ACE inhibitors and angiotensin-receptor blockers (ARBs) in earlier landmark heart failure trials ( Eur J Heart Fail. 2017 Jan;19[1]:43-53 ).
Dr. Fonarow views these data as “compelling.” These trials mark a huge step forward in the prevention of heart failure.
“We now for the first time in patients with diabetes have the ability to markedly prevent heart failure as well as cardiovascular death,” the cardiologist commented. “It is critical for cardiologists and heart failure specialists to play an active role in this [pharmacologic diabetes] management, as choice of therapy is a key determinant of outcomes, including survival.”
ACE inhibitors and ARBs
The ACC/AHA heart failure guidelines give a Class I recommendation to the routine use of ACE inhibitors or ARBs in patients at high risk for developing heart failure because of a history of diabetes, hypertension with associated cardiovascular risk factors, or any form of atherosclerotic vascular disease.
Lifestyle modification
Heavy drinking is known to raise the risk of heart failure. However, moderate alcohol consumption may be protective. In a classic prospective cohort study, individuals who reported consuming 1.5-4 drinks per day in the previous month had a 47% reduction in subsequent new-onset heart failure, compared with teetotalers in a multivariate analysis adjusted for conventional cardiovascular risk factors. Those who drank less than 1.5 drinks per day had a 21% reduction in heart failure risk, compared with the nondrinkers ( JAMA. 2001 Apr 18;285[15]:1971-7 ).
In the prospective observational Physicians’ Health Study of nearly 21,000 men, adherence to six modifiable healthy lifestyle factors was associated with an incremental stepwise reduction in lifetime risk of developing heart failure. The six lifestyle factors – a forerunner of the AHA’s Life’s Simple 7 – were maintaining a normal body weight, stopping smoking, getting exercise, drinking alcohol in moderation, consuming breakfast cereals, and eating fruits and vegetables. Male physicians who shunned all six had a 21.2% lifetime risk of heart failure; those who followed at least four of the healthy lifestyle factors had a 10.1% risk ( JAMA 2009 Jul 22;302[4]:394-400 ).
In a separate analysis from the Physicians’ Health Study, men who engaged in vigorous exercise to the point of breaking a sweat as little as one to three times per month had an 18% lower risk of developing heart failure during follow-up, compared with inactive men ( Circulation 2009 Jan 6;119[1]:44-52 ).
What’s next in prevention of heart failure
Heart failure is one of the most expensive health care problems in the United States, and one of the deadliest. Today an estimated 6.5 million Americans have symptomatic heart failure. But that’s just the tip of the iceberg.
“Countless millions more are likely to manifest heart failure in the future,” Dr. Fonarow warned, noting the vast prevalence of identifiable risk factors.
It’s time for a high-visibility public health campaign designed to foster community education and engagement regarding heart failure prevention, he added.
“We have a lot of action and events around preventing atherosclerotic cardiovascular disease. But can you think of any campaign you’ve seen focusing specifically on heart failure? Heart failure isn’t one of the endpoints in the ACC/AHA Atherosclerotic Cardiovascular Disease Risk Calculator or even the new hypertension risk calculator, so we need to take this a whole lot more seriously,” the cardiologist said.
The 2017 focused update of the ACC/AHA heart failure guidelines endorsed a novel strategy of primary care–centered, biomarker-based screening of patients with cardiovascular risk factors as a means of triggering early intervention to prevent heart failure ( J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803 ). This strategy, which received a Class IIa recommendation, involves screening measurement of a natriuretic peptide biomarker.
The recommendation was based on evidence including the STOP-HF randomized trial (St. Vincent’s Screening to Prevent Heart Failure Study), in which 1,374 asymptomatic Irish patients with cardiovascular risk factors were randomized to routine primary care or primary care plus screening with brain-type natriuretic peptide testing. Patients with a brain-type natriuretic peptide level of 50 pg/mL or more were directed to team-based care involving a collaboration between their primary care physician and a specialist cardiovascular service focused on optimizing guideline-directed medical therapy. During a mean follow-up of 4.2 years, the primary endpoint of new-onset left ventricular dysfunction occurred in 5.3% of the intervention group and 8.7% of controls, for a 45% relative risk reduction ( JAMA 2013 Jul 3;310[1]:66-74 ).
Dr. Fonarow reported receiving research grants from and serving as a consultant to the National Heart, Lung, and Blood Institute and a handful of medical companies.
