ApoA1 May Predict HF Outcomes Independently of CAD, Dyslipidemia

September 10, 2012

September 10, 2012 (Seattle, Washington) — Levels of apolipoprotein A1 (apoA1) significantly and independently predicted outcomes in patients with heart failure followed in a prospective observational study [1].

Elevated levels of the protein are considered to be protective against coronary artery disease, but in the current analysis, presented today here at the Heart Failure Society of America 2012 Scientific Meeting, the inverse association between apoA1 levels and an end point consisting primarily of death or transplantation was independent of CAD, dyslipidemia, and other CV risk factors.

Levels of apoA1 are associated with "a completely different pathophysiology than the regular biomarkers that we use [in heart failure], like [brain-natriuretic peptide] BNP," observed lead author Dr Vikas Bhalla (Emory University, Atlanta, GA) for heartwire . So it could potentially be included in multimarker panels for risk stratifying patients with heart failure and--perhaps--guide HF therapy, he said.

"We've already been optimizing our patients on beta blockers and ACE inhibitors and all the other [standard HF] drugs [based on current risk markers], so this is something of a different approach that might help our patients."

Indeed, Bhalla noted, the observed independent inverse relationship between apoA1 and risk of bad heart-failure outcomes supports the protein's involvement in a non-CAD heart-failure pathophysiology, inflammation being one candidate, said Bhalla. "It's very possible."

The analysis included a cohort of 173 ambulatory patients followed in the prospective, observational study from The Atlanta Cardiomyopathy Consortium (TACC). At baseline their mean LVEF was 29%; 34% had diabetes, 40% had coronary artery disease, 51% had dyslipidemia, and 30% had chronic kidney disease.

Patients with baseline apoA1 levels in the highest tertile had one-third the rate of the primary end point of death, transplantation, or LV-assist-device (LVAD) implantation compared with the lowest tertile over a mean follow-up of about 2.7 years. The events included 29 deaths, six heart transplantations, and three LVAD implantations.

Rate of the Primary End Point by Baseline ApoA1 Concentration, With Mean Levels per Tertile

Parameter <117 mg/dL 118–135 mg/dL >135 mg/dL
Mean apoA1 (mg/dL) 104.7 126.5 155.8
Death, transplantation, or LVAD (%) 34.5 21.7 10.5*

*p<0.01 vs lowest tertile

Other correlates of the primary end point included systolic blood pressure, LVEF, and diabetes. But in a multivariate analysis, apoA1 levels predicted the primary end point (p<0.01) independently of age, race, sex, diabetes, hypertension, dyslipidemia, CAD, smoking history, creatinine, systolic blood pressure, heart rate, LVEF, beta-blocker use, and use of ACE inhibitors or angiotensin II receptor blockers (ARBs).

Significant Differences in CV Risk Factors Between Patients With vs Without a Primary Event (Death, Cardiac Transplantation, or LVAD)

Parameter No primary event Primary event P
ApoA1 (mg/dL) 161.1 132.5 <0.01
Systolic BP (mm Hg) 111.8 103.5 <0.01
LVEF (%) 30.7 23.9 <0.02
Diabetes (% of patients) 29.6 50 <0.02
Kidney disease (% of patients) 25.4 47.4 <0.01

Bhalla said that following the current analysis, he and his colleagues observed that levels of apoA1 and BNP were inversely related. Patients in the lowest apoA1-concentration tertile corresponded to those in the highest BNP-concentration tertile, and vice versa. The high levels of BNP that suggest a poor heart-failure prognosis are a reflection of increased volume overload, he observed, while the low levels of apoA1 that--according to this analysis--are associated with a bad outcome are related to an entirely different mechanism.

"So we looked into a way of combining these biomarkers and found that we can improve the net reclassification" of HF patients into high- and low-risk status. When they combined tertiles of apoA1 and BNP as predictors, "the negative predictive value went pretty high," Bhalla said, "and improved the prognostication more than BNP alone would tell us."

If future studies show that treatment guided by apoA1 levels improves HF outcomes, given that current medical therapy of heart failure is aimed more at the BNP-related pathophysiologic pathway, observed Bhalla, "it would [represent] a completely new line of therapeutics for heart failure."

Bhalla declares he has no conflicts of interest.

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