Heart Failure May Share Etiology With . . . Osteoporosis?

July 09, 2014

CAMBRIDGE, UK — The rate of incident heart failure was inversely related to bone-mineral density, possibly signaling they have a shared pathophysiology, say researchers from a prospective, long-term cohort study[1]. Their analysis showed that the link between HF and bone-mineral density was strongest in patients whose heart failure was likely nonischemic.

The study, which measured bone-mineral density in the heel as broadband ultrasound attenuation (BUA), saw an independent 23% drop in HF risk with every one-standard-deviation rise in BUA.

"Our findings give support for cardiac assessment in people with reduced bone-mineral density and warrant further exploration of underlying biological mechanisms," write the authors, led by Dr Roman Pfister (Heart Center of the University of Cologne, Germany), in a report published today in JACC: Heart Failure. They say the findings, along with other research, suggest that "low bone-mineral density, and, in consequence, osteoporosis . . . are new markers that indicate increased risk for heart failure, independent of established risk factors."

The group followed 13 666 people for HF events over a mean of 9.3 years after they underwent BUA measurement by quantitative ultrasound of the heel bones, as part of the European Prospective Investigation into Cancer and Nutrition (EPIC) conducted in Norfolk, UK. The participants entered the study in the 1990s.

The adjusted risk of incident HF in quartiles 2, 3, and 4 for increasing BUA, each compared with quartile 1, fell significantly by 60%, 46%, and 54% respectively (p=0.002 for trend). The hazard ratio (HR) for incident HF per standard-deviation increase in BUA was 0.77 (95% CI 0.66–0.89).

The risk per standard-deviation BUA increment also fell significantly (p=0.001) among those developing heart failure without preceding MI: HR 0.75 (95% CI 0.63–0.89). But decreases were nonsignificant or only a trend among those with preceding MI (p=0.17) or with asymptomatic systolic dysfunction (p=0.07).

Results were similar when events in the first two years of follow-up were censored and after researchers excluded subjects with a history of osteoporosis or fracture and, in separate analyses, those using diuretics, steroids, nonsteroidal anti-inflammatory drugs, or calcium or vitamin-D supplements, respectively.

Adjusted* Hazard Ratios (95% CI) for Incident HF by Bone Density by Broadband Ultrasound Attenuation in EPIC

End points HR (95% CI) p
Excluding events during first 2 y 0.77 (0.66–0.90) 0.001
Excluding history of osteoporosis/fractures 0.81 (0.69–0.95) 0.008
Excluding diuretic medication 0.80 (0.68–0.93) 0.004
Excluding steroid/NSAID use 0.76 (0.64–0.91) 0.003
Excluding calcium/vitamin-D supplements 0.72 (0.61–0.87) <0.0001
*Per standard-deviation increase in BUA, adjusted for age, sex, body-mass index, systolic blood pressure, diabetes, cholesterol, current smoking, alcohol consumption, physical activity, "manual occupational social class," and education

Proposed mechanisms for the association between the measure of bone-mineral density and HF risk included: the two conditions share common risk factors; underlying coronary artery disease leads to both conditions; and shared pathophysiology. The group's arguments lean toward shared pathophysiology, which they contend is biologically plausible.

An accompanying editorial states that "the mechanism(s) for this association is almost certainly multifactorial" but seems to agree that shared pathophysiology may play a role[2]. Drs Kenneth W Lyles and Cathleen S Colon-Emeric (Duke University and VA Medical Centers, Durham, NC) mull the implications of indirect measures of bone-mineral density, already obtained for osteoporosis screening, as telling markers of future heart-failure risk. They also speculate on whether treatments aimed at improving bone-mineral density might also lower HF risk.

"The next step after such a provocative finding will be to replicate the association in another large database," they write.

The authors report that they have no relevant relationships. Lyles and Colon-Emeric disclose that they are founders and equity owners of BisCardia.

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