One in four deaths among women with heart failure can be attributed to kidney problems

About one in four deaths among women with heart failure can be attributed to kidney problems, and more deaths are linked to renal insufficiency than to any other single risk factor, according to a new study in the Oct. 19, 2004 issue of the Journal of the American College of Cardiology.

“Even mild renal insufficiency is associated with increased risk of mortality,” said Kirsten Bibbins-Domingo, Ph.D., M.D., at San Francisco General Hospital and the University of California in San Francisco.. “The women with mild renal disease in our study had an average serum creatinine of 1.2 milligrams per deciliter — a value that many clinicians might view as normal. If women with mild renal insufficiency were treated with ACE inhibitors, they no longer had an increased risk of death. Taken together these finding suggest that mild renal disease is a very common risk factor for death in women with heart failure that, if recognized by clinicians, can be reversed through treatment with ACE inhibitors,” Dr. Dr. Bibbins-Domingo said.

The researchers analyzed data on 702 women with heart failure who were participants in the Heart and Estrogen/progestin Replacement Study (HERS). The study did not include any patients undergoing kidney dialysis treatment. During an average follow-up period of almost six years, 228 of the women with heart failure died (32 percent). Renal insufficiency was strongly associated with mortality, even after the researchers took in account other conditions, heart pumping function and medications. Patients with renal insufficiency who were taking ACE inhibitor medication had the same risk of death during the study period as patients with normal kidney function.

Dr. Bibbins-Domingo said this study helps fill important gaps in understanding the effect of kidney problems on heart failure patients. Earlier studies focused on men with heart failure. Female patients tend to have a different mix of other diseases or conditions, and they are also more likely to have preserved systolic function, which means their heart failure is primarily related to difficulty filling the heart chamber with blood, rather than problems squeezing the blood out of the heart. In this study, the link between kidney function and mortality was seen for both patients with preserved systolic function and those with depressed systolic function.

“Prior studies examined men and these studies focused almost exclusively on heart failure with depressed systolic function. Women are more likely to have heart failure with preserved systolic function and no studies have focused on renal disease in this clinical entity. Our study is among the first to recognize that renal disease is one of the most important risk factors for death in heart failure with preserved systolic function in women,” Dr. Bibbins-Domingo said.

Although this study did not directly investigate how kidney disease makes heart failure more dangerous, she said it makes sense that the two conditions could conspire against patients.

“The heart and kidney failing at the same time is a very bad combination, probably because of synergistic effects of malfunctioning in both organs. The kidneys are needed to maintain normal fluid volume in the body —— when volume increases as kidneys fail, heart failure worsens. Worsening heart failure worsens renal function because the kidneys need adequate blood supply from the heart to function properly. Both heart failure and kidney insufficiency lead to other abnormalities, such as anemia, which in turn worsens both heart and kidney disease,” she said.

Dr. Bibbins-Domingo emphasized the need for physicians to recognize even mild kidney problems in their heart failure patients and to make appropriate use of ACE inhibitors, while closely monitoring electrolytes and progression of kidney disease. She added that it is also important to pay attention to other risk factors, including diabetes, heart arrhythmias, smoking and a lack of physical activity.

“Patients and doctors can do something about many of these risk factors to improve survival. Patients with heart failure should stop smoking and engage in an exercise program, under the supervision of their doctor. Doctors should make judicious use of ACE inhibitors, with close monitoring, among their patients with mild renal disease,” she said.

Norman E. Lepor, M.D., F.A.C.C., at Cedars-Sinai Medical Center and the University of California at Los Angeles, who was not connected with this research, said this article raises questions about why renal insufficiency would be associated with heart failure. He said the findings suggest that researchers need to further investigate the role of anemia and its relationship to both kidney and heart disease.

“Bibbins-Domingo et al. have contributed much to our understanding of the role kidney function plays in the prognosis of heart failure patients. Certainly, further work needs to be done to understand what it is about renal insufficiency that affects patients with cardiovascular disease and how to use treatments such as angiotensin converting enzyme inhibitors that attenuate this risk," he said.

Dr. Lepor also remarked on the observation that the signs of abnormal kidney function in these patients may be at low levels that often may be overlooked by clinicians.

“The irony regarding the patients with cardiovascular disease and in particular heart failure is that those with renal insufficiency who could benefit the most from treatment, such as angiotensin converting enzyme inhibitors and antiplatelet drugs, are more likely to have these therapies withheld,” Dr. Lepor added.

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