Outline
Primordial Prevention of Cardiovascular Disease and Heart Failure, 487
Disease Prevention in Stage a Heart Failure, 490
Hypertension and Heart Failure, 490
Diabetes Mellitus and Heart Failure, 493
Atherosclerotic Disease and Heart Failure, 495
Metabolic Syndrome and Heart Failure, 495
Obesity and Heart Failure, 496
Disease Prevention in Stage B Heart Failure, 496
Identifying Patients with Structural Cardiac Alterations for Preventive Therapy, 496
Use of Risk Scores for Prediction of Incident Heart Failure, 496
Use of Biomarkers for Screening and Prevention of Heart Failure, 497
Use of Imaging for Evaluation of Newly Suspected or Potential Heart Failure, 499
Future Directions, 500
Prevention of heart failure is an urgent public health need with national and global implications. Despite recent advances in the therapy of cardiovascular disorders, heart failure remains a challenging disease with a high prevalence ( Fig. 35.1 ) and a dismal long-term prognosis. On the basis of data from the National Health and Nutrition Examination Survey (NHANES) 2011 to 2014, an estimated 6.5 million Americans 20 years of age or older had heart failure. This represents an increase from an estimated 5.7 million United States adults with heart failure based on the NHANES 2009 to 2012. The “aging of the population” and improved survival and “salvage” of patients with acute myocardial infarction are believed to be some factors contributing to this growing burden of heart failure. Projections show that the prevalence of heart failure will increase 46% from 2012 to 2030, resulting in greater than 8 million people 18 years of age or older with heart failure ( see also Chapter 18 ).
It becomes evident that the heart failure burden will not be eliminated by an improvement in the survival of patients who are already affected with the disease; instead, a drastic reduction in the incidence of heart failure is required to prevent an increase in the heart failure burden. It is therefore important that we develop a population-level strategy to prevent the lifetime risk of heart failure that applies to the large number of “at-risk” individuals. Such a strategy would complement our current approaches that are aimed at intensive management of patients with manifest heart failure ( Fig. 35.2 ). The burden of heart failure risk factors and the effect of their prevention and treatment on incident heart failure are examined in this chapter. Because the primary mechanisms of the development of heart failure may be cardiac (structural remodeling, impaired contractility, decreased compliance) or peripheral (arterial stiffening, impaired arterial vasodilator reserve, fluid retention), this discussion is an attempt to characterize the specific mechanisms of the effect of the predisposing conditions and their treatment on the development of heart failure.
Given the sizeable public health burden posed by heart failure and limited health care resources, it is critical to identify the primary “drivers” of this problem. In 2001 a new approach to the classification of heart failure was adopted by the American College of Cardiology/American Heart Association which emphasized both the evolution and progression of the disease and which included stage A patients who are at high risk for developing heart failure but have no structural disorder of the heart and stage B patients with structural disorders of the heart but who have never developed symptoms of heart failure. This new classification scheme adds a useful dimension to our understanding of heart failure, recognizing that there are established risk factors and structural prerequisites for the development of heart failure and that therapeutic interventions performed even before the appearance of left ventricular dysfunction or symptoms can prevent the development of heart failure. The progression of the structural changes that lead to heart failure mandates that an all-out effort be made to slow or halt this progression. The best time to intervene would probably be in stage B, when the early structural changes can be identified but they have not yet progressed to the symptomatic phase of the disease.
Primordial Prevention of Cardiovascular Disease and Heart Failure
Functional and structural changes of the cardiovascular system progress with aging in all individuals. The rate of this progression is under the influence of genetic and environmental contributors. These functional and structural changes will eventuate in a morbid event if other factors do not end life before the cardiovascular changes have reached their symptomatic stage. Most morbid events are complications of progressive changes in the artery walls, whereas heart failure represents a complication of functional and structural changes in the myocardium.
Certain risk factors have been statistically associated with the early development of cardiovascular diseases, thus implying that these risk factors may accelerate the age-related changes in the health of the arteries or heart. The role of heredity versus environment on the development of these risk factors remains uncertain. Blood pressure, cholesterol, obesity, and even smoking may be related to genetic and environmental factors. Pharmacologic management of blood pressure and cholesterol have been shown in prospective trials to slow progression of disease and delay morbid events, but the efficacy of dietary and exercise interventions have not been documented. Preventing or treating these risk factors has nonetheless been a mission of American health agencies, as reflected in the goals of the American Heart Association to reduce the burden of disease ( Table 35.1 ). Public health efforts to promote a healthy environment and healthy lifestyle might therefore delay progression of disease in at least some individuals, but for the health care professional the goal is to identify individuals in need of pharmacologic intervention to slow disease progression.
| Health Metric | |
|---|---|
| 1 | Nonsmoking |
| 2 | Body mass index <25 kg/m 2 |
| 3 | Physical activity at goal levels |
| 4 | Dietary pattern that promotes cardiovascular health |
| 5 | Untreated total cholesterol <200 mg/dL |
| 6 | Untreated blood pressure <120/<80 mm Hg |
| 7 | Fasting blood glucose <100 mg/dL |
Therefore, in regard to heart failure, the public health efforts to prevent risk factors may be viewed as a prudent effort to forestall the symptomatic phase of the disease, but intervention pharmacologically to slow the progressive structural changes in the left ventricle (stage B heart failure) is the responsibility of the medical profession.
Although prevention of heart failure in individuals with stage A heart failure who already have known risk factors is important, once predisposing conditions are present, substantial elevations in long-term and lifetime risks for cardiovascular disease and heart failure are largely unavoidable. It is therefore important to focus on prevention before the development of risk factors. Prevention of cardiovascular disease and heart failure should start with healthy lifestyle education. In 2010 the American Heart Association created a new set of national goals for cardiovascular health promotion and disease reduction. Specifically the American Heart Association committed itself to achieving the following central organizational goals: “By 2020, to improve the cardiovascular health of all Americans by 20%, while reducing deaths from cardiovascular diseases and stroke by 20%.” These goals require new strategic directions for the American Heart Association in its research, clinical, public health, and advocacy programs for cardiovascular health promotion and disease prevention in the current decade and beyond. The goals introduce the concept of ideal cardiovascular health, which is defined by the absence of clinically manifest cardiovascular disease together with the simultaneous presence of optimal levels of seven health metrics (see Table 35.1 ), including four health behaviors (nonsmoking, body mass index less than 25 kg/m 2 , physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and three ideal health factors (untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, and fasting blood glucose <100 mg/dL). Greater adherence to the American Heart Association’s Life’s Simple 7 guidelines was shown to be associated with a lower lifetime risk of heart failure and better cardiac structure and functional parameters by echocardiography. Among 20,900 male physicians in the Physicians Health Study, healthy lifestyle habits (normal body weight, not smoking, regular exercise, moderate alcohol intake, consumption of breakfast cereals, and consumption of fruits and vegetables) were individually and jointly associated with a lower lifetime risk of heart failure, with the highest risk in men adhering to none of the six lifestyle factors and the lowest risk in men adhering to four or more desirable factors. These data confirm an association between lifestyle and disease, but they do not document cause and effect. Such documentation would require an expensive and robust intervention trial, which has not yet been successfully conducted. Because prevention of cardiovascular disease should ideally start in childhood, the American Heart Association developed the Life’s Simple 7 for kids to help children understand how small lifestyle choices might affect their cardiovascular health.
The potential importance of nonsmoking, healthy dietary pattern, and physical activity for the ideal cardiovascular health have been reviewed extensively elsewhere. Here, the existing evidence is provided as it relates to the prevention of cardiovascular disease and heart failure.
Smoking
Tobacco use is a major risk factor for cardiovascular disease and appears to have a multiplicative effect with the other major risk factors for coronary artery disease, such as high serum levels of lipids, untreated hypertension, and diabetes mellitus. Since the first report on the health dangers of smoking was issued by the United States Surgeon General in 1964, age-adjusted rates of smoking among adults have declined, from 51% of males smoking in 1965 to 16.7% in 2015 and from 34% of females in 1965 to 13.7% in 2015. The decline in smoking, along with other factors (including improved treatment and reductions in the prevalence of risk factors such as uncontrolled hypertension and high cholesterol), is a contributing factor in the sharp decline in the heart disease death rate during this period.
Although the majority of ex-smokers report that they quit without any formal assistance, cessation medications (including sustained-release bupropion, varenicline, and nicotine gum, lozenge, nasal spray, and patch) are effective for helping smokers quit. In addition to medications, smoke-free policies, increases in tobacco prices, cessation advice from health care professionals, and quit-lines and other counseling have contributed to smoking cessation.
Physical Activity
Being physically active is associated with good health, and being inactive is associated with poorer health. Physical activity may improve risk factors for cardiovascular disease (such as blood pressure and cholesterol level) and reduce the likelihood of coronary artery disease, type 2 diabetes mellitus, myocardial infarction, stroke, and premature mortality.
The American Heart Association guidelines on physical activity recommend that children get at least 60 minutes of physical activity daily and that adults get at least 150 minutes of moderate intensity or 75 minutes of vigorous-intensity aerobic activity per week and perform muscle strengthening activities at least 2 days/week. In the Health Professionals Follow-Up Study, for every 3-hour-per-week increase in vigorous-intensity activity reported, there was a 22% lower risk of myocardial infarction, and this could be explained in part by beneficial effects of physical activity on high-density lipoprotein cholesterol, vitamin D, apolipoprotein B, and hemoglobin A 1c . A meta-analysis of nine cohort studies, representing 122,417 patients, found that as little as 15 minutes of daily moderate to vigorous physical activity was associated with reduced all-cause mortality in adults 60 years of age or older. This potential protective effect of physical activity appeared to be “dose dependent,” because the greatest reduction in mortality per minute of greater physical activity was for those at the lowest levels of physical activity. These findings suggest that older adults may benefit from physical activity time far below the amount recommended by the federal guidelines.
Moderate physical activity is associated with a lower long-term incidence of heart failure, preventing cardiac injury and neurohormonal activation. In patients with heart failure, intense activity (an aerobic interval-training program three times per week for 12 weeks) was associated with a an improvement in left ventricular ejection fraction and decreases in pro-B-type natriuretic peptide (proBNP), left ventricular end-systolic and end-diastolic volumes compared with control and endurance-training groups. Exercise training in patients with heart failure with preserved ejection fraction was associated with improved exercise capacity and favorable changes in diastolic function.
Healthy Dietary Pattern
Dietary habits affect multiple cardiovascular risk factors, including both established risk factors (systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol levels, high-density lipoprotein cholesterol levels, glucose levels, and obesity/weight gain) and novel risk factors (e.g., inflammation, cardiac arrhythmias, endothelial cell function, triglyceride levels, lipoprotein[a] levels, and heart rate). Sodium linearly raises blood pressure in a dose-dependent fashion, with stronger effects among older people, hypertensive people, and African Americans, and induces additional blood pressure–independent damage to renal and vascular tissues. Estimated sodium intake of more than 3.7 g/day was associated with adverse cardiac remodeling and worse systolic strain and diastolic e′ velocity, which may predispose to heart failure.
Among 17 leading risk factors in the United States in 2010, suboptimal dietary habits were most prominently associated with mortality. In 2010 a total of 678,000 deaths of all causes were associated with suboptimal diet. A previous investigation reported the estimated mortality effects of several specific dietary risk factors in 2005 in the United States. High dietary salt consumption was estimated to be potentially responsible for 102,000 annual deaths, low dietary omega-3 fatty acids for 84,000 annual deaths, high dietary trans fatty acids for 82,000 annual deaths, and low consumption of fruits and vegetables for 55,000 annual deaths.
The 2015 US Dietary Guidelines Advisory Committee summarized the evidence for benefits of healthful diet patterns on a range of cardiometabolic and other disease outcomes. They concluded that a healthy dietary pattern is higher in vegetables, fruits, whole grains, low-fat or nonfat dairy, seafood, legumes, and nuts; moderate in alcohol (among adults); lower in red and processed meat; and low in sugar-sweetened foods and drinks and refined grains. Greater versus lower adherence to a Mediterranean dietary pattern, characterized by higher intakes of vegetables, legumes, nuts, fruits, whole grains, fish, and unsaturated fat and lower intakes of red and processed meat, was associated with a lower risk of incident coronary heart disease and stroke. Although higher conformity with the Mediterranean dietary pattern has been associated with lower risk of cardiovascular mortality in a primary prevention cohort, adherence to the Mediterranean diet in patients already afflicted with heart failure did not influence long-term mortality after an episode of acute heart failure, but it was associated with decreased rates of rehospitalization during the next year.
During recent decades, consumption of red meat has been increasing globally, especially in developing countries. At the same time, there has been growing evidence that high consumption of red meat, especially of processed meat, may be associated with an increased risk of major chronic diseases, including type 2 diabetes mellitus, cardiovascular disease, and cancer, and increased mortality risk.
Recent years have brought interesting insights into the human gut microbiota and have highlighted its potential impact on cardiovascular diseases, including heart failure. Changes in composition of gut microbiota, called dysbiosis, can trigger systemic inflammation, which is known to be involved in the pathophysiology of heart failure. Studies have suggested a role for the intestinal microbiota in the pathogenesis of atherosclerosis in patients with a diet rich in phosphatidylcholine (with major sources including eggs, liver, beef, and pork) through the formation of the metabolite trimethylamine and conversion to trimethylamine- N -oxide (TMAO). The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota ( Fig. 35.3 ). Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events such as heart failure, chronic kidney disease, myocardial infarction, stroke, or death.
Recent evidence suggests that adherence to a healthy plant-based diet is associated with lower risk of coronary heart disease and heart failure. Eating at least five servings of fruit and vegetables every day while avoiding processed foods (which have high salt content) and fried foods, and eating lean meats like fish and poultry provide a well-balanced, heart-healthy diet. Although an increasing number of studies showed an inverse association of certain dietary components such as nut consumption or moderate alcohol consumption with cardiovascular disease and heart failure, the evidence that these and other lifestyle choices affect cardiovascular disease progression in an individual patient is not persuasive.
Disease Prevention in Stage a Heart Failure
Stage A heart failure is defined as people without heart failure symptoms or structural heart disease but with predisposing conditions for heart failure. This classification is used to identify high-risk patients to prevent progression to structural heart disease or symptomatic heart failure. It is estimated that one-third of the US adult population is living with predisposing conditions for heart failure (i.e., are in stage A heart failure), many of whom are not adequately recognized or being appropriately or adequately treated for their risk factors.
A number of risk factors have been identified that may lead to heart failure. These exert their adverse effects through functional and structural influence on the left ventricle, characterized as ventricular remodeling and defined as progressive ventricular hypertrophy, enlargement, and cavity distortion over time. The clinical syndrome of heart failure usually results from both impaired left ventricular performance and congestion secondary to sodium and fluid retention.
The risk factors for heart failure include hypertension, diabetes mellitus, atherosclerotic disease, metabolic syndrome, obesity, chronic kidney disease, and the use of many therapeutic and recreational agents that can exert cardiotoxic effects. Coronary heart disease, hypertension, smoking, diabetes mellitus, and obesity appear to be responsible for 52% of incident heart failure cases in the population, with their population attributable risks shown in Table 35.2 . Valvular heart disease is responsible for an additional 2% of incident heart failure cases in the population. The pathogenetic role of predisposing conditions/comorbidities in the development of heart failure with preserved ejection fraction is illustrated in Fig. 35.4 . As shown, comorbidities induce systemic inflammation. Chronic inflammation, in turn, affects the lungs, myocardium, skeletal muscle, and kidneys, leading to diverse heart failure with preserved ejection fraction phenotypes. These predisposing conditions/comorbidities are, by and large, preventable with currently known and available strategies. A recent study on 34,736 participants in the Women’s Health Study showed that women with new-onset atrial fibrillation who achieved or maintained optimal risk factor control (obesity, smoking, elevated blood pressure, and diabetes mellitus) exhibited a lower heart failure risk.
| Risk Factor | Population Attributable Risk (%) |
|---|---|
| Coronary heart disease | 20 |
| Hypertension | 20 |
| Cigarette smoking | 14 |
| Diabetes mellitus | 12 |
| Obesity | 12 |
| Valvular heart disease | 2 |
Hypertension and Heart Failure (see also Chapter 25 )
Considerable evidence from experimental and clinical studies and epidemiologic investigations indicates the critical role of hypertension in the pathogenesis of heart failure. In an observational study including more than 1 million adult patients 30 years of age or older, higher systolic blood pressure and diastolic blood pressure were associated with increased risk of cardiovascular disease incidence and angina, myocardial infarction, heart failure, stroke, peripheral artery disease, and abdominal aortic aneurysm, each evaluated separately. Higher blood pressure in midlife is a harbinger of increased risk of heart failure in later life, thus suggesting that early risk factor modification may decrease heart failure burden. Data from the Framingham Heart Study (FHS) indicate that recent (within the past 10 years) and remote antecedent blood pressure levels could be an important determinant of cardiovascular disease and heart failure risk over and above the current blood pressure level. The 44-year follow-up of the FHS showed that 75% of heart failure cases have antecedent hypertension. In addition, hypertension is frequently accompanied by metabolic risk factors and obesity, which themselves increase the risk of heart failure. Hypertension is the most powerful pathogenetic factor in the development of heart failure with preserved ejection fraction. This strong relationship has led some authors to propose that heart failure with preserved ejection fraction may be a later stage of hypertensive heart disease.
Although many genes or gene combinations influence blood pressure, poor diet, physical inactivity, and excess intake of alcohol, alone or in combination, may be an important contributor to hypertension. Some of the diet-related factors associated with high blood pressure include overweight and obesity, excess intake of sodium, and insufficient intake of potassium, calcium, magnesium, protein (especially from vegetables), fiber, and fish fats.
Progression from chronic hypertension to structural ventricular changes, and then to asymptomatic diastolic and systolic ventricular dysfunction, is well established by natural history investigations from longitudinal epidemiologic cohort studies, such as the FHS. Elevated blood pressure places greater hemodynamic burden on the myocardium and leads to left ventricular hypertrophy ( Fig. 35.5 ). Left ventricular hypertrophy is associated with increased myocardial stiffness and decreased compliance, initially during exercise and subsequently at rest. The initial concentric hypertrophy (thick wall, normal chamber volume, and high mass-to-volume ratio), per the Laplace’s law, helps to keep wall tension normal despite high intraventricular pressure ( Fig. 35.6 ). Because systolic stress (afterload) is a major determinant of ejection performance, normalization of systolic stress helps to maintain a normal stroke volume despite the need to generate high levels of systolic pressure. Constriction and stiffening of small arteries at branch points and in the microcirculation augment reflected waves that may impose a late systolic aortic pressure load on left ventricular emptying that is not detectable in the arm ( Fig. 35.7 ). Therapy that relaxes these small arteries may therefore exert a greater benefit than is apparent from standard blood pressure measurement.
A new guideline for the prevention, detection, evaluation, and management of high blood pressure in adults was recently proposed. It changed the definition of hypertension, which is now considered to be a systolic blood pressure of 130 mm Hg or higher or a diastolic blood pressure of 80 mm Hg or higher. According to these new criteria, % of adults in the United States have high blood pressure. Strategies to control blood pressure are an integral part of any effort to prevent heart failure.
Prevention of hypertension and treatment of established hypertension are complementary approaches to reducing cardiovascular disease risk in the population, but prevention of hypertension provides the optimal means of reducing risk and avoiding the harmful consequences of hypertension. The updated guideline presents new treatment recommendations for patients with hypertension, which include lifestyle changes and blood pressure–lowering medications. Correcting the dietary aberrations, physical inactivity, and excessive consumption of alcohol that cause high blood pressure is a potentially important approach to prevention and management of high blood pressure, either on their own or in combination with pharmacologic therapy. However, hereditary factors may predominate, and drug management may be necessary to supplement nonpharmacologic interventions such as behavioral strategies aimed at lifestyle change, prescription of dietary supplements, or implementation of kitchen-based interventions that directly modify elements of the diet. At a societal level, policy changes can enhance the availability of healthy foods and facilitate physical activity.
Aggressive blood pressure control may be the most effective approach to reduce the incidence of heart failure in a hypertensive population. A number of clinical trials demonstrate the benefit of treating hypertension in the prevention of heart failure. For instance, Hypertension in the Very Elderly trial showed a 64% relative risk reduction in heart failure with the diuretic indapamide with or without the angiotensin-converting enzyme (ACE) inhibitor perindopril ( Fig. 35.8 ).
Diabetes Mellitus and Heart Failure (see also Chapter 48 )
On the basis of data from NHANES 2011 to 2014, an estimated 23.4 million adults have diagnosed diabetes mellitus, 7.6 million adults have undiagnosed diabetes mellitus, and 81.6 million adults (33.9%) have prediabetes (e.g., fasting blood glucose of 100 to <126 mg/dL). The number of patients with diabetes mellitus continues to rise, owing mainly to changes in lifestyle (excessive calorie and fat intake and decreased physical activity). The total prevalence of diabetes in the United States is expected to more than double from 2005 to 2050 (from 5.6% to 12.0%) in all age, sex, and race/ethnicity groups. On the basis of NHANES 2011 to 2014 data for adults with diabetes mellitus, 20.8% had their diabetes mellitus treated and controlled, 46.4% had their diabetes mellitus treated but uncontrolled, 9.9% were aware they had diabetes mellitus but were not treated, and 22.9% were undiagnosed and not treated ( Fig. 35.9 ).
Diabetes mellitus is a major risk factor for cardiovascular disease, such as coronary heart disease, stroke, peripheral artery disease, heart failure, and atrial fibrillation. In the Multi-Ethnic Study of Atherosclerosis (MESA), diabetes mellitus was associated with a twofold increased adjusted risk of incident heart failure among 6814 individuals free of cardiovascular disease at baseline over a mean follow-up of 4 years.
The occurrence of heart failure represents a major and adverse prognostic turn in a diabetic patient’s life. Heart failure is the most common admission diagnosis for the diabetic patient, and more than one-third of type 2 diabetic patients die of heart failure. The presence of diabetes mellitus conferred a greater risk for heart failure hospitalization despite contemporary management of cardiovascular disease in 19,699 patients studied in the international REduction of Atherothrombosis for Continued Health (REACH) registry.
The basic reason for the increased prevalence of heart failure in the diabetic patient may be the presence of a distinct diabetic cardiomyopathy that is structurally characterized by cardiomyocyte hypertrophy, microangiopathy, endothelial dysfunction, and myocardial fibrosis. Doppler imaging studies not only have confirmed evidence of diastolic dysfunction in asymptomatic patients with diabetes but also have shown a direct relationship between the extent of diastolic dysfunction and glycemic control ( Fig. 35.10 ).
Although neither the Diabetes Control and Complications Trial (DCCT) in type 1 diabetes nor the UK Prospective Diabetes Study (UKPDS) in type 2 diabetes showed a reduction in cardiovascular events with intensive glycemic control, a prospective, observational component of UKPDS revealed a continuous relationship between glycemic exposure and the development of heart failure with no threshold of risk, such that for each 1% lower glycosylated hemoglobin (HbA 1c ), there was a 16% lower risk for heart failure ( Fig. 35.11 ). Similar findings were also reported in a large cohort study from the United States. The Atherosclerosis Risk in Communities (ARIC) study demonstrated that chronic hyperglycemia before the development of diabetes contributed to risk of heart failure. Glucose levels predict hospitalizations for congestive heart failure, with a 10% increase in the risk of heart failure hospitalization for each 18-mg/dL (1-mmol) increase in fasting glucose level.
