Prevention of Heart Failure in Patients with Diabetes

Stage A Heart Failure

Among patients with diabetes, coexisting risk factors for HF such as atherosclerotic diseases, hypertension, and obesity increase the risk of developing subsequent LV dysfunction. These risk factors are highly prevalent among patients with diabetes and represent an important clustering of modifiable risk factors to consider for population-targeted intensive risk factor intervention for HF prevention. From population studies, the prevalence of stage A HF among individuals aged 45 years or older is approximately 20%. The underlying assumption is that by aggressively treating these modifiable risk factors underpinning the hazard for HF, the risk of progression to overt LV dysfunction could be mitigated. As these CV risk factors often coexist and contribute to other diabetes CV complications, lifestyle modification and pharmacologic treatments aimed at treating such risk factors may lead to multifaceted CV risk reduction, including but extending beyond risk for HF.

Stage B Heart Failure

Stage B heart failure refers to structural and functional cardiac abnormalities without overt clinical manifestations of HF, based predominantly on cardiac imaging results. For practical purposes, it has been narrowly defined as previous MI with regional dysfunction or scar, left ventricular hypertrophy (LVH), left ventricular systolic dysfunction (LVSD; or reduced ejection fraction [EF]), or structural valve disease. Based on data from cross-sectional population studies, stage B HF is estimated to affect approximately one third of the population 45 years of age or older. The magnitude of this at-risk group suggests that a significant proportion of the population may benefit from early identification of abnormal LV structure and function so that preventive interventions may be applied most efficiently. This is also an important group to target for clinical trials of early pharmacologic intervention for systolic and diastolic dysfunction.

Among the subcategories of stage B HF, LVSD has been the most studied. Depending on the age of the population studied and the EF threshold chosen to characterize abnormal LV function, the prevalence of asymptomatic LVSD in predominantly middle-aged and elderly adults ranges from 2% to 10%, with higher rates reported among men and older adults ( Box 25-1 ). Asymptomatic LVSD is associated with markedly increased risk of developing clinical HF and is associated with higher mortality risk compared with patients having similar risk factor profiles but without evidence of LVSD. In the Framingham cohort, 26% of participants with asymptomatic LVSD progressed to symptomatic HF during the 5-year follow-up, representing an approximately fivefold increased risk compared with subjects with normal LV function. This was associated with a 60% higher mortality risk, but, more important, over half of the deaths occurred before symptomatic HF developed. Although most studies examining the risk of stage B HF progressing to symptomatic HF have included predominantly older white individuals, in a large cohort of white and black young adults (18 to 30 years old at baseline), the presence of asymptomatic LVSD was a strong predictor of incident HF (greater than 30 times the rate compared with individuals with normal EF) before the age of 50 years, independent of other clinical risk factors, including blood pressure (BP). Given the irrefutable evidence suggesting stage B HF as a precursor to symptomatic HF and its associated risk of mortality, targeting diabetic patients with stage B HF for aggressive preventive measures may meaningfully modify the trajectory of the disease progression into symptomatic HF.

Box 25-1

Data from Nesto RW, Bell D, Bonow RO, et al: Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003, Circulation 108:2941-2948, 2003.

Risk Factors Associated with Increased Risk of Heart Failure (HF) in Diabetic Patients Treated with Thiazolidinediones (TZDs)

• History of HF (either systolic or diastolic)

• History of prior MI or symptomatic coronary artery disease

• Hypertension

• LVH

• Significant aortic or mitral valve heart disease

• Advanced age (> 70 years)

• Longstanding diabetes (> 10 years)

• Preexisting edema or current treatment with loop diuretics

• Development of edema or weight gain on TZD therapy

• Insulin coadministration

• Chronic renal failure (creatinine > 2.0 mg/dL)

Screening with Clinical Risk Factors

As described, several well-established clinical risk factors, including the diagnosis of diabetes, increase the risk of incident HF and should be used by clinicians to identify those at-risk patients who will benefit from aggressive risk factor modification and primary prevention. Advantages of this strategy are their broad availability and generalized feasibility for clinicians even in areas of limited health care resources. Nevertheless, despite the well-documented association of individual risk factors for HF, quantifying the magnitude of risk for an individual patient in the presence of multiple risk markers may be challenging. Validated HF risk scores, such as those derived from the Framingham Heart Study and the Health, Aging, and Body Composition (Health ABC) Study, allow both clinicians and researchers to systematically risk-stratify patients into various risk levels for development of overt HF. Although these risk scores are not specific for patients with diabetes, diabetes and elevated fasting blood glucose have been consistently found to be independent predictors for incident HF. In addition, increased risk of HF identified by the risk scores is associated with subclinical cardiac structural and functional alterations that may lead to overt HF. Among adults 30 to 65 years old, observations from the population-based Dallas Heart Study demonstrated that the prevalence and severity of increased LV mass, LVH concentric remodeling, and LVSD identified with cardiac magnetic resonance imaging (cMRI) incrementally increased across the risk strata defined by the Health ABC risk scores. These observations provided some pathophysiologic underpinnings to support the use of risk scores for identification of individuals at increased risk of incident HF.

Several limitations exist with regard to use of risk prediction scores as a screening strategy. The risk scores mentioned earlier were derived from population studies with either predominantly white participants (Framingham Heart Study) or only white and black participants (Health ABC study), and both studies included only individuals from the United States. This may limit the generalizability of these risk scores in other populations. There also remains a lack of validated risk scores derived specifically from patients with diabetes. Furthermore, despite the availability and validity of these risk scores, in practice appropriate risk stratification and implementation of risk modification interventions are often suboptimal during routine clinical encounters. Recent data from the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2010 showed that although achievement of recommended treatments goals for HbA1c, BP, and low-density lipoprotein cholesterol (LDL-C) among patients with diabetes has improved during the last decade, there remains significant room for further optimization ( Fig. 25-2 ). Therefore, there clearly remains an unmet need to effectively translate risk prediction model results into a clinical tool to further advance efforts in prevention of HF through aggressive management of these risk factors. One potential direction is to capitalize on the evolution of integrated health systems and the increasing use of electronic health data, whereby an automated analysis and summary of documented risk elements yielding an estimation of risk could be included in the patient care fields to allow for continuous screening for risk and assessment of efficacy of relevant interventions. Such a process could also generate clinical alerts to inform screening and therapeutic modifications. (See also Chapter 31 .)

Screening with Biomarkers

In theory, biomarkers are biologic variables that are capable of providing information about the presence, severity, and prognosis of a condition of interest. In practice, the term biomarker in HF is limited to circulating serum and plasma analytes that reflect various aspects of the pathophysiology of HF beyond routine hematology and biochemistry panels. To be clinically useful, a particular biomarker must be shown to provide additional information that may alter clinical decision making or guide interventions, above and beyond careful clinical assessment.