Demographic Distribution

HF is a disease of older adults. In a recent population-based report from the United Kingdom, mean age at diagnosis was 76.7±12.6 years. A similar median age (76–77 years) at HF diagnosis was reported for inpatients in Denmark, with most patients diagnosed between age 66 and 85. In Canada, although patients diagnosed in specialty clinics were slightly younger (median, 69 years) compared with general clinic outpatients (72 years), and those diagnosed in the emergency department (75 years) were younger compared with inpatients (77 years), the majority of cases in the population were diagnosed between ages 57 and 84.

Men and women are equally affected by HF. However, age at onset and type of HF affect sex predominance. In the United Kingdom, women accounted for 49.0% of new HF cases. A similar 1:1 sex ratio for new cases has been reported in the United States around the world. However, although higher rates of coronary artery disease in men lead to male preponderance in younger patients, susceptibility to diastolic dysfunction leads to a higher proportion of women affected by HF at older ages. Men are more likely to develop HF with reduced EF (HFrEF), whereas women are more prone to HF with preserved EF (HFpEF). In the United Kingdom, age at diagnosis in men was 74±13 years versus 79±12 years in women. A similar difference has been reported in Sweden. Finally, in large studies, HF appears to affect all races equally.

Comorbidities (see also Chapter 48 )

As a disease of older adults, HF is rarely encountered in isolation. More than 80% of patients have ≥2 concomitant chronic conditions, and most have ≥3. The most common are hypertension, ischemic heart disease, diabetes mellitus, cerebral and peripheral vascular disease, atrial fibrillation, chronic kidney disease, chronic obstructive lung disease, anemia, and depression. As average age at HF diagnosis increases over time, the number of comorbidities and medications in patients with HF increases as well. In the United Kingdom, the number of comorbidities in patients with HF increased from 3.4±1.9 in 2002 to 5.4±2.5 in 2014, and the percentage of patients with ≥3 additional conditions increased from 68% to 87%. In the US National Health and Nutrition Examination Survey (NHANES), the average number of prescription medications in patients with HF increased from 4.1 in 1988–1994 to 6.4 in 2003–2008. Overall, there is a shift from a model where HF was mainly a consequence of coronary artery disease with male preponderance toward a disease of older adults equally affecting both sexes and accompanied by a complex medical profile. Among the 493 older adults (age 70–79 years at inception) who developed HF in the Health, Aging, and Body Composition Study, 36.8% had no prior coronary artery disease.

Estimates and Trends

Most contemporary national health care databases in developed countries indicate that the age-standardized incidence of HF at the population level is declining, and that age-standardized prevalence of HF is increasing only slightly, the latter being probably the result of advances in HF therapeutics. However, because of population aging, the crude incidence remains high and the crude prevalence and number of patients with HF keeps increasing. Estimates vary according to the methods and definitions used. The population incidence of HF is currently estimated between 200 and 400 cases annually per 100,000 individuals in most developed countries, and the crude prevalence ranges between 1% and 3%. Table 18.1 summarizes the population prevalence of HF in health care databases around the world.

In a comprehensive epidemiologic study from the United Kingdom, the population-based incidence of HF in 2014 was 332/100,000 person-years, a 7% decline from 2002; the decline was similar for men and women. Despite this decline, crude incidence increased by 2% and the number of new HF cases increased by 12% between 2002 and 2014, largely due to an increase in population size and age. In the same study, although the age- and sex-standardized prevalence of HF increased only slightly from 1.5% to 1.6%, the number of patients with HF increased by 23% over the same period.

Similar trends have been reported in North America and continental Europe. In a study of 2.3 million Medicare beneficiaries (age ≥65), although incident HF declined by 32% between 2004 and 2013, prevalence increased from 16.2% to 17.2%. In Olmsted County, Minnesota, the adjusted incidence of HF declined from 316/100,000 in 2000 to 219/100,000 in 2010. The decline was greater for HFrEF than for HFpEF. In Ontario, Canada, HF incidence decreased by 32.7% between 1997 and 2007 (from 455 to 306/100,000 person-years), with a comparable decrease in both inpatient and outpatient settings. In Sweden, despite a relative decline in incidence by 24% between 2006 and 2010 (average, 380 cases per 100,000 person years), the prevalence of HF remained unchanged. In Germany, the age- and sex-standardized incidence of HF in 2006 was 270/100,000 person years. In Italy, the incidence of hospitalized new HF cases in Lombardy decreased between 2005 and 2012 (from 362 to 313/100,000 adults), but with an increasing proportion of patients aged ≥85 years. However, in a study of in-hospital new HF cases in Denmark between 1995 and 2012, although HF incidence declined overall and in older persons (>50 years), there was an increasing trend in younger (≤50 years) persons.

Impact of Demographics and Socioeconomic Status

Age

Age is a major contributor to development of HF, and therefore the incidence and prevalence of HF is considerably higher among middle-aged or older adults. In a meta-analysis of community-based studies, the median prevalence of HF among persons age ≥60 was 11.8% (4.7%–13.3%). The effect of age on HF prevalence is demonstrated in the NHANES data ( Fig. 18.1 ). Among Danish adults, the annual incidence of new in-hospital HF diagnosis in 2012 was <0.01% in ages 18 to 35 but >1% in ages >74 ( Fig. 18.2 ) . In the United States, the annualized incidence of HF ranges between 1% and 2% among older adults (age ≥65), depending on age group and race.

Prevalence of heart failure by gender and age in the United States.

From US National Health and Nutrition Examination Survey, 2011–2014.

Incidence of in-hospital heart failure diagnosis among adults in Denmark, 2012.

Data from Christiansen MN, Køber L, Weeke, et al. Age-specific trends in incidence, mortality, and comorbidities of heart failure in Denmark, 1995 to 2012. Circulation . 2017;135:1214–1223 .

Lifetime Risk of Heart Failure

In a project that pooled more than 700,000 person-years of follow-up in the United States (85% white, 15% black), lifetime risk for HF at age 45 was estimated at 30% to 42% in white men, 20% to 29% in black men, 32% to 39% in white women, and 24% to 46% in black women. Lifetime risk for HF was higher with higher blood pressure and body mass index (BMI) at all ages. Women are more likely to develop HF as the first manifestation of cardiovascular disease.

Prevalence of Preclinical (Stage A and B) Heart Failure

As with most chronic diseases, HF is a progressive condition amenable to early preventive interventions (see also Chapter 35 ) . To emphasize this concept, the American Heart Association and the American College of Cardiology have proposed a scheme that classifies HF into four stages. Stage A indicates the presence of risk factors but no clinical or subclinical disease. Stage B refers to asymptomatic cardiac structural or functional abnormalities usually detectable by cardiac imaging (i.e., subclinical disease). Stage C refers to stable symptomatic HF, whereas Stage D is used to indicate advanced symptomatic HF that is refractory to pharmacotherapy.

Because of the need for systematic imaging to detect subclinical disease, limited data exist on the population prevalence of HF stages. In the Atherosclerosis Risk in Communities (ARIC) study, among 6,118 participants age 67 to 91 years, 52% were categorized as Stage A and 30% as Stage B in the 2011–13 visit. In the Framingham study, among 6770 participants (54% women) with a mean age of 51, the prevalence of Stage A and B was 36.5% and 24.2%, respectively. The prevalence of Stage B increased steadily with age, from 17.6% in the ≤54 age group to 42.9% in the ≥75 age group ( Fig. 18.3 ) . Compared with healthy participants, mortality was twofold higher among participants with Stage B HF after a mean of 7 years.

Prevalence of heart failure stages in the Framingham Heart Study, Massachusetts.

Data from Xanthakis V, Enserro DM, Larson MG, et al. Prevalence, neurohormonal correlates, and prognosis of heart failure stages in the community. JACC Heart Fail . 2016;4:808–815.

Heart Failure After Acute Coronary Syndromes (see also Chapter 19 )

Coronary artery disease is a major driver of HF. Previous longitudinal studies have shown that reductions in short- and long-term mortality after acute myocardial infarction (AMI) in the past decades have been translated into increasing rates of HF. In recent registries, post-AMI HF is declining, as a result of increasing use of early interventional strategies. However, HF continues to be a major problem in patients recovering from AMI or acute coronary syndrome (ACS). Estimates of HF after AMI vary as a result of varying definitions of both AMI and post-AMI HF.

Among Medicare beneficiaries (age ≥65) in the United States, rates for HF within 1 year after AMI declined modestly from 16.1% in 1998 to 14.2% in 2010. Similar trends, albeit at lower absolute HF rates due to a more stringent definition, have been reported for Australia. Among 25,000 patients without HF admitted for a first ACS in Alberta, Canada, between 2002 and 2008, HF during index admission occurred in 13.6% of patients with ST-elevation AMI, 14.8% of those with non-ST-elevation AMI, and 5.2% of those with unstable angina. Incident HF rates at 1 year were 23.4%, 25.4%, and 16.0%, respectively, indicating that HF continues to be a common complication of AMI. Revascularization was associated with 18% lower risk for HF after the index admission. In a Swedish national registry, primary percutaneous coronary intervention increased from 6.0% to 91.5% between 1996 and 2008, accompanied by a decrease in the incidence of HF (defined as presence of crackles or the use of IV diuretics or inotropes) during index hospitalization from 46% to 28%. The decrease was more pronounced for ST-segment elevation AMI. Notably, reduction in post-AMI HF rates has been reported for HFrEF but not HFpEF. In a comprehensive study from Norway, 18.7% of patients developed new HF during index admission for a first AMI between 2001 and 2009, depending on age ( Fig. 18.4A ) . Among patients discharged without HF, 12.6% were admitted or died because of HF after a median of 3.2 years. The annual incidence of HF was 3.1% in men and 4.6% in women ( P < .01) (see Fig. 18.4B ). Risk for HF was highest during the first 6 months of follow-up.

Heart failure after first acute myocardial infarction (A) during index admission and (B) post index admission in Norway, 2001–2009.

Data from Sulo G, Igland J, Nygård O, et al. Prognostic impact of in-hospital and postdischarge heart failure in patients with acute myocardial infarction: a nationwide analysis using data from the Cardiovascular Disease in Norway [CVDNOR] project. J Am Heart Assoc. 2016;5:e002667.

Hypertension (see also Chapter 25 )

Along with coronary artery disease, hypertension has the highest population-attributable risk for HF. In the Health ABC Study (age 70–79 at inception), there was a continuous direct association between systolic blood pressure (SBP) and HF risk for levels of SBP as low as <115 mm Hg. The 10-year incidence of HF with SBP <120, 120 to 139, 140 to 159, and ≥160 mm Hg at baseline was 5.9%, 10.5%, 14.8%, and 22.8%, respectively, and more than half of cases occurred in individuals with SBP <140 mm Hg. The impact of SBP control on HF risk was impressively demonstrated in the landmark Systolic Blood Pressure Intervention Trial (SPRINT), which compared intensive (<120 mm Hg) with conventional (<140 mm Hg) target SBP; intensive SBP target reduced risk of HF by 37% (HR 0.63; 95% CI, 0.46–0.85; P = .003) consistently across all subgroups.

Older adults and black patients with hypertension are especially vulnerable to HF. In the Second Australian National Blood Pressure Study (ANBP2), which compared an angiotensin-converting inhibitor-based versus a thiazide diuretic-based regimen in hypertensive patients aged 65–84 years, the incidence of HF was 0.63% per year; 0.79% in men and 0.48% in women over a median of 10.8 years, without difference between arms. The 5-year incidence of HF was 3.0% in hypertensive patients aged 55 to 80 without HF assigned to either losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial; however, the incidence was higher among black versus nonblack patients (7.0 vs. 3.1%).

Diabetes (see also Chapter 48 )

Several studies have highlighted the impact of increasingly prevalent metabolic risk factors, including diabetes, glucose intolerance, and insulin resistance on HF risk. Glycemic control appears to be directly associated with HF risk. In the Swedish National Diabetes Registry, among patients with type 1 diabetes (age, 39±13 years; 45% women), the incidence of new hospitalized HF was 340 events per 100,000 patient-years and increased monotonically with hemoglobin A1c (HbA1c), with a range of 140 to 520 events per 100,000 patient-years between patients in the lowest (<6.5%) and highest (≥10.5%) categories of HbA1c. In the same registry, poor glycemic control (HbA1c >7%) was associated with increased risk of hospitalization for new HF in type 2 diabetes (age, 66±12 years; 45% women); the annualized incidence increased significantly, from 1.38% for patients with HbA1c <6.0% to 2.58% for patients with HbA1c ≥10.0%. Risk was higher for men, older patients, and longer diabetes duration. However, in a study that modeled HbA1c as a time-updated variable in ∼8700 individuals with type 2 diabetes, both HbA1c <6% (HR 1.60; 95% CI, 1.38–1.86) and HbA1c >10% (HR 1.80; 95% CI, 1.60–2.16) were associated with risk of HF, pointing to a U -shaped relationship between HbA1c and HF precipitation.

Obesity

Obesity and associate metabolic derangements are important drivers of HF from a public health perspective. In the Cardiovascular Lifetime Risk Pooling Project, lifetime risk for HF was higher with higher body mass index (BMI) at all ages in both blacks and whites, and did not diminish substantially with advancing index age. In the MESA prospective cohort, a multicenter observational cohort study following 6814 subjects (mean age 62±10 years; 47% men), BMI has been identified as an independent predictor of HF with 40% higher risk for every 5 kg/m ² higher BMI (HR 1.40; 95% CI 1.10–1.80). However, the increased risk for HF with obesity may be largely mediated by obesity-related conditions. In the MESA study, the associations of BMI and waist circumference with incident HF became nonsignificant after adjusting for obesity-related conditions (hypertension, dysglycemia, hypercholesterolemia, left ventricular hypertrophy, kidney disease, and inflammation).

Atrial Fibrillation (see also Chapter 38 )

Atrial fibrillation (AF) is common among patients with HF and worsens prognosis. Conversely, AF confers increased risk for HF, especially HFpEF. In the Framingham Heart Study, among 1,737 individuals with new AF (mean age, 75±12 years; 48% women), more than one-third (37%) had HF. Conversely, among 1166 individuals with new HF (mean age, 79±11 years; 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HFpEF versus HFrEF. In Olmsted County, Minnesota, among approximately 3,500 patients with new AF (age 71±15 years, 45.5% women), a substantial excess risk of HF was observed after AF diagnosis, with a standardized morbidity ratio of 9.60, 2.13, and 1.70 at 90 days, 1 year, and 3 years, respectively. Among patients with EF data, 61% had HFpEF (EF ≥50%) and 39% had HFrEF (EF <50%). In the community-based Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), among ∼6500 outpatients with AF in the United States (median age 74 years, 43.6% female) annualized HF incidence was 1.58% over a 2-year follow-up period, with a higher proportion of HFpEF versus HFrEF. Of note, in contrast to general HF cases, the incidence of HF after AF does not seem to be declining in recent years.

Renal Disease

Renal impairment is common in HF and portends a worse prognosis. Conversely, HF commonly follows renal dysfunction. In a study of ∼10,000 men (mean age, 67 years), an estimated glomerular filtration rate (eGFR) <60 mL/min per1.73 m ² was associated with a twofold risk of HF compared with eGFR ≥60 mL/min per 1.73 m ² after a median of 10 years. Even moderate renal impairment, despite the absence of diabetes and hypertension, was associated with a higher risk of HF. A similar increase in HF risk was observed in three community cohorts in the United States, pooling data from ∼14,500 participants (age, 63±12 years; 59% women; 44% black), where chronic kidney disease (CKD—defined as <60 mL/min per 1.73 m ² ) was present in 10% of participants. Annualized incidence of HF was 2.20% among those with versus 0.62% without CKD. Risk for HF was higher in blacks and Hispanics. Besides CKD, acute kidney injury also carries HF risk. In a cohort of 300,000 hospitalized US veterans without HF, a 0.3-mg/dL or 50% increase in serum creatinine from baseline to peak hospital value was associated with 23% increased 2-year risk for HF. Of note, in a cohort of more than 3500 patients with CKD, cystatin C-based eGFR and albuminuria predicted risk for HF better than creatinine-based eGFR; anemia, insulin resistance, inflammation, and poor glycemic control were additional risk factors.

Trends in Hospitalization Rates

Hospitalization for decompensated (or “acute”) HF has become the epicenter of intensive research (and debate), both from a therapeutic and a health care perspective. Hospitalization represents a turning point in the natural history of HF, with a striking increase in adverse outcomes afterwards. Many therapies have been evaluated for acute HF, but none has been shown to improve outcomes. The pathophysiologic mechanisms that lead to increased mortality and morbidity after hospitalization for HF are still uncertain. Hospitalization rates and trends vary widely across health care systems, as financial and administrative incentives are different. Recent reports from the United States and other countries report a decrease in hospitalizations for HF. However, these trends are not consistent across health care systems, and the total burden of HF hospitalizations remains high, secondary to population aging and increasing HF prevalence.

In the United States, annual hospitalization rates for HF as a primary diagnosis among adults ≥18 years declined from 553/100,000 people in 2001–2005 to 489/100,000 in 2006–2019 and 416 in 2010–2014. However, the rates for HF as a secondary diagnosis remained stable at ∼1400 admissions per 100,000 people annually. In France, the overall age-standardized rate of primary HF hospitalizations was 250/100,000 people in 2012, with only a small change from 2002. Of note, although the age-standardized rate was higher in men (320 vs. 200/100,000 people), the crude rate was comparable between men and women. In Germany, primary HF-related hospitalizations increased by 65.4% between 2000 and 2013, and by 28.4% after age adjustment (from 261 to 335/100,000), and HF was the leading cause of hospitalizations and in-hospital deaths in 2013. In Murcia, Spain, crude hospitalization rates for a primary diagnosis of HF increased by 76.7% between 2003 and 2013, from 128 to 226/100,000 people, and rates doubled in persons ≥75 years. Importantly, the Elixhauser comorbidity index increased by ∼1 point during the study period and episodes, with >6 points increased by twofold.

Length of Stay

Length of stay is highly system dependent. In the large Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, mean length of stay ranged from 4.9 to 14.6 days across 27 countries. In a nationally representative sample of primary HF hospitalizations in the United States, mean length of stay declined from 6.1 days in 1996 to 5.3 in 2009. However, despite attempts to shorten length of stay worldwide, the burden of HF on hospitals has proven difficult to curb. In Germany, the absolute number of HF-related hospital days increased by 22% from 2000 to 2013, despite a 26% decrease in the average length of stay (from 14.3 to 10.6 days). Also, data from registries and clinical trials indicate that there is a trade-off between length of stay and short-term readmission rates in patients admitted for HF.

Effect of Heart Failure Hospitalization on Outcomes

Hospitalization has a dramatic impact on HF outcomes, especially mortality, that is evident in both short- and long-term studies. In the Italian HF registry, 1-year mortality was 24% among patients admitted for HF (19.2% for de novo HF and 27.7% for worsening HF) and 5.9% in outpatients. In the European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) registry, all-cause 1-year mortality rate was 23.6% for inpatient versus 6.4% for outpatient enrollees. The corresponding composite endpoint of mortality or HF hospitalization within 1 year was 36.0% and 14.5% for inpatients and outpatients, respectively. Among Medicare beneficiaries with new-onset HF between 2004 and 2013 in the United States, unadjusted 1-year mortality was 31.9% and 13.5% for HF diagnosed as inpatient and outpatient, respectively. In the CHARM clinical trial program, which enrolled ∼7600 patients with New York Heart Association class II to IV HF, rates of cardiovascular mortality and HF hospitalization were more than 50% higher among patients with previous HF hospitalization (71% of patients) over a median follow-up of 3 years. The magnitude of increased risk was similar in patients with HFrEF or HFpEF, and varied inversely with the time interval between hospitalization and enrollment.