Preventing Heart Failure
I. Heart Failure: What every physician needs to know.
II. Diagnostic Confirmation: Are you sure your patient has Heart Failure?
A. History Part I: Pattern Recognition
- B. History Part 2: Risk Factors
C. History Part 3: Competing diagnoses that can mimic Heart Failure.
D. Physical Examination Findings.
E. What diagnostic tests should be performed?
1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- Long-term management.
- IV. Management of Co-Morbidities
I. Heart Failure: What every physician needs to know.
Heart failure prevalence continues to increase. Currently over 6 million Americans have heart failure.
This is partly related to aging of the population; better care of acute cardiovascular diseases, where now patients survive but with poor cardiac function; and also the worsening risk factor profile in the community with increasing prevalence of heart failure risk factors, including obesity and diabetes.
Similar trends are seen globally. Incidence and prevalence of heart failure is highest among the elderly. With the growing elderly population in the United States and the aging of the baby boomers, these epidemiologic trends are projected to get significantly worse.
In fact, according to a recent American Heart Association policy statement forecasting the future of cardiovascular diseases in the United States, over the next two decades, it appears that the proportional increase in heart failure prevalence will be higher than any other major cardiovascular diseases.
Couple this with the fact that outcomes of patients once they develop heart failure, both clinical and quality of life, remain poor, these trends underscore and emphasize the importance of heart failure prevention. In order to increase the emphasis on heart failure prevention, the American College of Cardiology and the American Heart Association (ACC/AHA) now classify individuals into four stages:
A. Those without structural heart disease but at risk for heart failure (e.g., individuals with hypertension and diabetes)
B. Those with structural heart disease but not symptoms of heart failure (e.g., those with asymptomatic valvular heart disease or left ventricular hypertrophy)
C. Those with symptomatic heart failure
D. Those with advanced heart failure.
ACC/AHA Heart Failure Staging classification signifies that many individuals have underlying risk factors and structural abnormalities that if detected and treated aggressively, would potentially lead to a significantly lower risk of developing heart failure and other adverse cardiovascular outcomes.
Prevention of coronary heart disease has been a major focus of research and clinical practice for several decades now, including development of risk prediction schemes, clinical trials, and management recommendations to prevent risk for coronary heart disease. Such intense focus has been lacking for heart failure prevention.
However, many opportunities remain to detect and treat patients aggressively to reduce the risk of heart failure. Considering the current and projected heart failure epidemiologic trend, such attempts are important and are likely to have a major impact on individual and societal health.
II. Diagnostic Confirmation: Are you sure your patient has Heart Failure?
A. History Part I: Pattern Recognition
Although primarily the management of individuals from heart failure prevention perspective requires lifestyle management and aggressive treatment of comorbidities, equally important is to keep a low threshold for assessing signs and symptoms in patients without a history of heart failure that may indicate underlying left ventricular dysfunction. Dyspnea, the uncomfortable awareness of breathing, is the most common symptom.
If can be abrupt in onset in individuals presenting with pulmonary edema, but more often than not, it presents with subtle progression in individuals who lessen their usual activity rather than pursue medical attention. It may occur with exertion, at rest, or in the recumbent position signifying orthopnea and paroxysmal nocturnal dyspnea, and underlying fluid accumulation.
Other common symptoms may include unexplained edema and fatigue. The presence of nausea or vomiting, early satiety, or right upper quadrant discomfort, nocturnal cough, or nocturia among other symptoms should all alert a clinician to search for possible left ventricular dysfunction.
B. History Part 2: Risk Factors
Many studies have described various risk factors for developing heart failure, ranging from lifestyle factors to comorbidities; medications, laboratory and imaging characteristics; to novel biomarkers and genomic markers. Heart failure risk increases proportionally with advancing age and male gender.
Behavioral risk factors include sedentary lifestyle, coffee consumption, and increased salt intake. Low socioeconomic status has been associated with increased risk. Hypertension, diabetes, obesity, sleep apnea, renal dysfunction, and coronary artery disease are risk factors. Physical inactivity, or sedentary time, was associated with an elevated risk for heart failure in the First National Health and Nutrition Examination Survey. Using data from the California Men's Health Study, investigators confirmed that lower sedentary time and higher physical activity have independent and consistent associations with reductions in heart failure incidence.
Laboratory parameters associated with risk include microalbuminuria and levels of homocysteine, insulin like growth factor, proinflammatory cytokines, B-type natriuretic peptide, serum resistin, lipoprotein associated phospholipase A2, and myeloperoxidase levels. Several chemotherapeutic agents (e.g., doxorubicin, trastuzumab, cyclophosphamide, and 5-fluorouracil) are associated with heart failure.
There is growing interest in discovering the genomic predictors of heart failure. Genetic alterations in functional pathways (e.g., energy production, regulation [e.g., mitochondrial mutations]), calcium cycling abnormalities (e.g., RyR2 mutations), and mutations in transcriptional regulators (e.g., Nkx2.5 leading to ventricular hypertrophy) are associated with higher risk. Genetic polymorphisms in sympathetic receptors (e.g., the genes coding for α2C adrenergic receptors (α2C del322-325) or β1 adrenergic receptors (β1 Arg389) are associated with risk.
Risk factors and population attributable risk
Population attributable risk represents the proportional reduction in disease risk that may be achieved by eliminating the risk factor from the population, assuming a causal relationship. In a report from the Health ABC Study, a cohort of well-functioning, community-dwelling older adults, coronary heart disease and uncontrolled blood pressure were the leading causes of heart failure in whites, blacks, men, and women.
A large proportion of heart failure, however, was also attributed to metabolic and cardio-renal factors, including glucose and renal abnormalities. Several previous investigations have reported substantial sex- and race-related differences in population attributable risks for heart failure.
The higher incidence of heart failure in black compared to white participants in the Health ABC Study was accompanied by a higher prevalence of risk factors in black participants. Black participants not only had a higher proportion of overall risk factors but also specifically those risk factors which are potentially amenable to intervention, which translated the population attributable to risk in general to a higher modifiable fraction in black individuals (68% vs. 49% in whites).
Identifying high risk Individuals
Most studies on heart failure risk factors have studied individual risk factors and only two studies have developed a prediction model for new onset heart failure. The Framingham Heart Failure Risk Score study assessed the probability of developing heart failure over a 38-year follow-up, with 6,354 person examinations in men and 8,913 in women.
The investigators developed a 4-year event score with an event rate averaging 3.97 per 100-person year in men and 2.63 in women, with a 37% increment per decade of age. The Health ABC Heart Failure Risk Model was developed using the data from 2,935 individuals participating in the Health ABC Study.
The mean age of the population was 73.6 years, with 52% females and 41% blacks. Independent predictors of heart failure included age, history of coronary heart disease and smoking, systolic blood pressure and heart rate, serum glucose, creatinine, albumin levels, and electrocardiographic left ventricular hypertrophy; the model has good discrimination and calibration. A simple point score was created to predict the incidence of heart failure risk using four risk groups corresponding to <5%, 5% to 10%, 10% to 20%, and >20% 5-year risk.
C. History Part 3: Competing diagnoses that can mimic Heart Failure.
The diagnosis of heart failure can be challenging because of the nonspecific nature of the presenting symptoms. It is not uncommon for patients to receive multiple courses of antibiotics for suspected pneumonia, or to receive bronchodilators for suspected asthma or chronic obstructive pulmonary disease before the accurate diagnosis of heart failure is established.
In other cases, many patients with lower extremity edema are falsely assumed to have heart failure, when in fact there may be an underlying nephrotic syndrome, cirrhosis, chronic venous stasis, or an adverse medication effect (e.g., with calcium channel blockers). Conversely, other medical conditions may present with signs and symptoms that overlap with heart failure and should be ruled out (e.g., thyroid disorders, lung diseases, anemia, muscle disorders, or simply obesity). A thorough medical history and physical examination followed by targeted laboratory or imaging testing can often help establish the diagnosis.
D. Physical Examination Findings.
Many patients with dyspnea have clear lung fields on examination despite elevated filling pressure. Thus the clinical assessment of left-sided filling pressure relies heavily on the presence of symptoms (e.g., dyspnea, paroxysmal nocturnal dyspnea, orthopnea) and evidence of elevation in right-sided filling pressure (e.g., jugular venous distention, edema).
The assessment of right-sided congestion is the most important component of the physical examination in patients suspected of having heart failure. A study reported that the presence of elevated jugular venous pressure (>12 mm Hg) and hepatojugular reflux are the most sensitive findings (65%, 83%, respectively) correlating with a pulmonary capillary wedge pressure (PCWP) >22 mm Hg. Other important signs of congestion include the presence of an S3 gallop, edema of the lower extremities, ascites, scrotal edema, and hepatomegaly.
E. What diagnostic tests should be performed?
Many laboratory and imaging tests may aid in the diagnosis of heart failure; however, eventually the final diagnosis will require an echocardiogram or other forms of cardiac imaging to assess the cardiac structure and function.
1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
A number of laboratory tests can help diagnose heart failure. At the time of diagnosis, laboratory work should focus on evidence of heart failure and also of end-organ involvement, including assessment of renal function and liver abnormalities.
Perhaps the most important laboratory test in patients with unexplained symptoms is the use of natriuretic peptide testing, B-type natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP). Natriuretic peptides are secreted by the ventricle in response to increases in pressure, as can be seen in heart failure or aortic stenosis.
From a diagnostic perspective, the measurement of natriuretic peptide levels in patients with dyspnea outperforms clinical judgment for the diagnosis of heart failure. A cut-off of 100 pg/ml of BNP enables an accurate diagnosis in >80% of patients with dyspnea. It is important to realize that BNP can be elevated in disease processes other than heart failure, including acute pulmonary embolism, chronic obstructive pulmonary disease (COPD), and cor-pulmonale.
However, routine screening of asymptomatic individuals with natriuretic peptides is not recommended, since the test characteristics are not optimal for screening. For example, if the optimal BNP receiver operating characteristic curve value of 55 pg/ml is used to screen general population older than 45 years for asymptomatic systolic dysfunction, it will lead to 24% of the population to have an echocardiogram to assess further.
Of these, 96% will be normal. In addition, the screening process would still miss 10% of those with disease. Data for screening asymptomatic diastolic dysfunction are similar.
It is important to realize that natriuretic peptide levels may not reflect disease severity in individuals who are morbidly obese (levels are lower), elderly (levels are higher), and in patients with significant renal failure (levels are higher). In addition, women tend to have higher BNP levels than men. In patients with heart failure and preserved ejection fraction, BNP levels are lower than in patients with heart failure and reduced ejection fraction.
Biomarkers can be important tools for diagnosis and prognosis in heart failure. A recently developed, suppression of tumorigenicity (ST2) marker is implicated in cardiomyocyte stress and fibrosis that provides incremental value to natriuretic peptides for risk stratification and prognosis of patients with heart failure.
Several basic laboratory values can lend evidence to the severity of heart failure and may affect a patient’s prognosis. For example, the presence of hyponatremia is an indicator of more severe dysfunction and is associated with a worse prognosis.
Renal dysfunction also raises suspicion about the possibility of cardiovascular disease. Presence of anemia may be the cause of heart failure if severe, or may be caused secondary to heart failure, though usually both anemia and hyponatremia occurs in later stages of the disease and will be unlikely, unlike renal dysfunction, to be seen in early stages of the disease.
If the diagnosis is confirmed, consideration should be given to an extended diagnostic workup for etiologies of heart failure, including connective tissue diseases (e.g., antinuclear antibodies), hemochromatosis (percent transferrin saturation, ferritin), thyroid disease (thyroid stimulating hormone), amyloidosis (serum protein electrophoresis), and infection (human immunodeficiency virus), where appropriate.
2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
A basic chest x-ray can provide valuable information in patients suspected of heart failure. Examination of the lung fields may reveal signs of fluid overload in patients with dyspnea, including cephalization, interstitial edema, the presence of effusions, or Kerley B lines.
Of note, the absence of these findings does not rule out elevated filling pressure, as the lung lymphatics adapt to chronic pressure elevations by accommodating more fluid. More importantly, a chest x-ray may assist in the diagnosis of alternate diseases in patients presenting with dyspnea of unclear etiology (e.g., pneumonia). The presence of cardiomegaly (cardiac to thoracic width ratio >50%) is a marker of heart failure, as well as ventricular enlargement, although it may be seen with pericardial effusions also.
Echocardiography is the single most important test to consider when assessing a patient suspected of having undiagnosed left ventricular dysfunction or heart failure. An echocardiogram provides valuable information about the etiology and severity of heart failure and enables an accurate assessment of chamber dimensions, ventricular function, valvular stenosis/regurgitation, and filling pressure/patterns including diastolic function.
The presence of regional wall motion abnormalities suggests possible coronary disease. Alternative diagnoses may present with typical echocardiographic findings, including amyloid (biventricular thickening, small chamber size, restrictive physiology, “sparkling” echogenicity, and valve and atrial septal thickening) or hypertrophic cardiomyopathy (mitral systolic anterior motion, outflow tract obstruction, and asymmetric septal hypertrophy).
Careful assessment of diastolic function is warranted, as worsening degrees of diastolic dysfunction are linked with prognosis across the heart failure spectrum. The severity of pulmonary hypertension correlates more with degree of diastolic dysfunction than systolic dysfunction.
Recent advances have led to improved understanding of the role of genetics in cardiomyopathies, including hypertrophic, dilated, and restrictive cardiomyopathy; arrhythmogenic right ventricular dysplasia; and left ventricular non-compaction. It is estimated that 20% to 50% of idiopathic dilated cardiomyopathies are likely familial in origin, and mutations in more than 30 different genes have been identified.
When a familial cardiomyopathy is suspected, the clinician should obtain an extended family history dating back at least three generations. A thorough family history may enable the clinician to identify a pattern of inheritance (e.g., X-linked, autosomal dominant, recessive), the degree of penetrance, and age of onset of the disease. Most familial cardiomyopathies are inherited in an autosomal dominant manner, and a thorough family history will often prove to be useful.
Upon suspicion, screening should include a careful history and examination, electrocardiogram, and echocardiogram. The next step in the evaluation is the consideration of genetic testing.
Since determining which genetic tests are appropriate for an individual person is difficult, it is recommended that such individuals be referred to expert centers where cardiovascular genetic medicine is practiced. In general, genetic testing is recommended in the family member who presents with the most obvious phenotypic features of the disease (i.e., the proband).
This is done to facilitate future family screenings and appropriate management. If the primary affected family member tests positive for a known mutation, the first-degree relatives can then be tested for this same mutation and avoid being tested for all possible genes or mutations. Any asymptomatic family member who tests positive for the gene should undergo a full clinical screening evaluation and close surveillance.
Management of individuals at risk for heart failure requires:
A keen awareness and search for risk factors
Assessment of underlying cardiovascular abnormalities, when indicated by history and physical examination
Pursuing healthy lifestyle choices
Aggressive management of comorbidities that increase the risk for heart failure
The Dietary Approaches to Stop Hypertension (DASH) diet encourages consumption of more:
Fruits and vegetables
Grains and grain products
Lean meats, fish, poultry
Low fat or nonfat dairy food
Nuts, seeds, and legumes
Also reduce the consumption of red meat, fat, and sugar while maintaining a low sodium intake.
Initially, this diet was promoted for hypertension; however, recent evidence supports its beneficial effects on reduction of heart failure risk with an observed 37% lower heart failure rate in women who adhere to the DASH diet. The DASH diet may contribute to heart failure prevention in some cases because of a reduction in blood pressure and incidence of coronary heart disease.
The DASH diet reduces low-density lipoprotein cholesterol levels and oxidative stress. The relationship between several components of the DASH diet and heart failure has been investigated.
Daily consumption of whole-grain breakfast cereals was associated with a 30% lower rate of heart failure, consumption of eggs more than twice per day was associated with a 64% higher rate, consumption of fish was associated with a 20% to 31% lower heart failure rate depending of the frequency of consumption, and consumption of 100 mmol or more of sodium was associated with a 26% higher rate.
Sodium: Human ancestors consumed less than 0.25 grams of salt per day. The recent high salt intake of 10-12 g/day challenges physiologic systems in excretion of salt, resulting in a rise in blood pressure, and risk for cardiovascular and renal disease.
Currently the Department of Health and Human Services recommends that adults should consume no more than 2,300 mg/day of sodium (equal to approximately 1 tablespoon of salt), but specific groups (i.e., persons with hypertension, middle-aged, and older adults, and blacks) should consume no more than 1500 mg/day of sodium as recommended for all Americans by the American Heart Association's Presidential Advisory panel. Overall, 69.2% of U.S. adults meet the criteria for the risk groups. There is overwhelming evidence for a causal relationship between salt intake, and blood pressure and cardiovascular diseases. American Heart Association Science Advisory provides a framework by which observational studies relating sodium intake to cardiovascular outcomes can be analyzed.
A reduction in salt intake has beneficial effects on the cardiovascular system, independent of and additive to its effect on blood pressure and include regression of left ventricular hypertrophy and delay in deterioration of renal function. A high dietary intake of sodium could lead to heart failure because of increased blood pressure (pressure overload) or extracellular fluid (volume overload) and left ventricular hypertrophy.
Specific strategies should be implemented to target a lower intake of sodium. The food industry needs encouragement to reduce sodium. A public health campaign to educate consumers for the need to make wise and healthy choices in the sodium content of their food is important. Finally, the responsibility to use fresh products and avoid canned and other high salt food eventually falls on individuals. However, studies need to determine if variables such as heart failure subtype and severity, comorbidities, medical therapies, or salt sensitivity should affect a patient’s recommended daily sodium intake.
Whole Grain: There are several mechanisms by which whole grain cereals could protect against heart failure through effects on weight, hypertension, myocardial infarction, and diabetes mellitus. Nutrients contained in whole grain cereals (e.g., potassium may lower blood pressure, phytoestrogens may improve insulin sensitivity, and other constituents exert beneficial effects on lipid and homocysteine levels or possess antioxidant properties). Also, slowing starch digestion or absorption promotes satiety.
Fish: Fish consumption exerts beneficial effects on heart failure risk with about a 20% lower risk associated with an intake of 1 to 2 times per week and about a 30% lower risk with intake ≥ 3 times per week. Marine n-3 fatty acids was associated with 37% lower heart failure risk in the highest quintile of intake compared with the lowest.
Fish oil favorably affects hemodynamics and reduces blood pressure, inflammation, vascular responses, and myocardial oxygen consumption; augments left ventricular response to exercise; prevents left ventricular remodeling; and improves left ventricular indices and diastolic filling. Fish oil supplementation of 3 to 5 g/day may also reduce risk, whereas dietary doses of about 0.5 grams per day may result in more modest effects.
The beneficial associations were most pronounced when consuming broiled or baked fish at least 3 times per week, the equivalent of about 500 mg per day eicosapentaenoic acid and docosahexaenoic acid, while fried fish intake does not exert this benefit on heart failure risk. It has been reported that broiled or baked fish consumption is inversely associated with systolic blood pressure, C-reactive protein levels, and carotid intimal medial thickness, whereas fried fish intake is positively associated with them, indicated that type of cooking could impact the effects.
Physical inactivity is an important risk factor for heart failure. Evidence suggests that regular physical activity has important and wide ranging health benefits like reduction in risk of cardio-vascular diseases.
Emerging evidence indicates that maintaining a high level of daily low-intensity activity may be important independent of moderate-vigorous physical activity. Studies have linked prolonged sitting with cardiovascular risk independent of age or recreational energy expenditure. Physical activity is a key determinant of good health and an important component of weight reduction and weight maintenance, improved lipoprotein profile, and reduced risk of hypertension, diabetes mellitus, and coronary artery disease.
Physical activity also reduces left ventricular hypertrophy independent of body weight or blood pressure because of a reduction in vascular resistance, improved endothelial function, suppression of the renin-angiotensin and sympathetic nervous system activity, and reduction of insulin resistance. Chronic physical activity reduces cytokine production by adipose tissue, skeletal muscles, endothelial and blood mononuclear cells, and upregulates antioxidant enzymes.
Physiologic cardiac remodeling varies according to the specific hemodynamic load imposed, and manifests as eccentric remodeling with endurance training and concentric remodeling with resistance training. However, these remodeling patterns demonstrate remarkable plasticity. It is important to consider that changes with exercise may more accurately be viewed as restoring end-organ adaptations to a true physiologic baseline. Heart failure has also been implicated in respiratory muscle, especially, diaphragmatic fiber weakness. Aerobic exercise can protect against diaphragm contractile fiber dysfunction induced by heart failure.
Interventions: The recommendations of the American College of Sports Medicine and the American Heart Association for regular physical activity in healthy adults from 18 to 65 years include:
Aerobic Activity: Moderate-intensity aerobic physical activity for a minimum of 30 minutes on 5 days each week or vigorous-intensity aerobic activity for a minimum of 20 minutes on 3 days each week. A combination of moderate and vigorous intensity activity can be performed to meet this recommendation. Since walking is the preferred activity among sedentary individuals and the effects of walking have been reported as beneficial regarding primary prevention, this should be encouraged for individuals who do not adhere to the current recommendations.
Muscle-Strengthening Activity: It is recommended that 8 to 10 exercises should be performed on 2 or more nonconsecutive days each week using the major muscle groups. To maximize strength development, a resistance (weight) should be used that allows 8 to 12 repetitions of each exercise resulting in volitional fatigue. Muscle-strengthening activities include a progressive weight-training program, weight bearing calisthenics, stair climbing, and similar resistance exercises that use the major muscle groups.
Activity dose: Vigorous-intensity activities may have greater benefit than moderate-intensity physical activity.
Mobile health technology (mHealth): American Heart Association’s (AHA) scientific statement defines mHealth as, “ mHealth, a subsegment of eHealth, is the use of mobile computing and communication technologies (e.g., mobile phones, wearable sensors) for health services and information. The use of mHealth devices and various mobile device apps are now emerging as important means to improve, track and stimulate physical activity in heart failure patients.
Excessive alcohol consumption is associated with alcoholic cardiomyopathy, characterized by ventricular dilation, increased mass, and reduced or normal wall thickness. Limited data are available on the amount and duration of consumption with most studies reporting that patients with symptomatic heart failure had 10 years or more of exposure to heavy drinking.
Acute ethanol ingestion may also lead to depressed contractility. Besides the direct myocardial toxicity, excessive alcohol consumption increases the risk of heart failure by promoting hypertension, myocardial infarction, and diabetes.
Interestingly, controversial data suggest possible benefits of moderate alcohol consumption. Two cohort studies have reported a 47% and a 34% lower heart failure risk, respectively.
The Framingham Heart Study reported a 59% lower risk among men who consumed 8 to 14 drinks per week compared with abstainers. Moreover, it has been reported that light-to-moderate alcohol consumption is associated with 40% to 50% lower risk of heart failure with previous myocardial infarction, whereas in the same study the risk of heart failure without antecedent myocardial infarction among heavy drinkers was 1.7-fold higher than in abstainers.
Similar findings were reported in the Physicians’ Health Study. Beneficial effects of alcohol have also been reported on risk for hypertension, myocardial infarction, and diabetes mellitus, whereas alcohol seems to raise high-density lipoprotein cholesterol, improve insulin sensitivity, and lower inflammatory markers.
Current evidence supports a major role for drinking patterns. Binge drinking (defined as consumption of 3 or more alcoholic drinks within 1 to 2 hours) has deleterious health effects, whereas light-to-moderate alcohol consumption (1-2 drinks per day for men and 1 drink per day for women spread over several days of the week) appears to yield most of the beneficial health effects. Thus, for a given volume of alcohol within the moderate drinking range, it would be better to be distributed evenly throughout the week than to be consumed more rapidly.
Tobacco use is the most prevalent preventable cause of disease and premature death in the United States. Smoking is a strong predictor of heart failure, with a 45% to 88% increased risk, respectively, after adjustment for coronary heart disease.
In the Coronary Artery Surgery Study, smokers had 47% higher risk of heart failure. A cohort study in Sweden showed that smokers have a 60% higher risk for heart failure, and in the Health, Aging, and Body Composition Study current smokers had a twofold higher risk.
Population attributable risk of smoking for heart failure was 17% as reported in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, and 5.5% in whites and 15% in blacks as reported in the Health, Aging, and Body Composition Study. There is no safe level of smoking; single cigarette may stiffen the left ventricle and as few as 1 to 4 cigarettes a day double the risk of having a myocardial infarction.
Moreover, smoking cigarettes with lower yields of tar and nicotine have not been shown to lower risk of heart disease and should not be considered lower-risk alternatives. Mechanisms leading to heart failure in smokers include (1) indirect effects (i.e., by causing or aggravating comorbidities that are strongly related with heart failure) and (2) direct effects on the myocardium as smoking is associated with coronary vasoconstriction, abnormal endothelial function, increased ischemic burden, oxidative stress, increased peripheral vascular resistance, insulin resistance, and type 2 diabetes.
Interventions: All individuals should be asked about tobacco use, and smokers should be counseled to quit. Individuals should be referred to formal cessation programs. Current recommended strategies include:
Medications: Several effective medications are available for tobacco dependence. Seven first-line medications increase long-term smoking abstinence rates: bupropion SR, varenicline, and nicotine gum, inhaler, lozenge, nasal spray, or patch. Nicotine replacement therapy should be used with caution among particular cardiovascular patient groups.
Counseling and Psychosocial support: Individual, group, and telephone counseling (problem solving/skills training) and social support are effective and their effectiveness increases with treatment intensity.
Body mass index is associated with heart failure in a positive and linear fashion in both sexes. Abdominal obesity is a stronger predictor for heart failure than total obesity.
A strong association is known between abdominal adiposity and features of metabolic syndrome, insulin resistance, and inflammation, all of which have been related to heart failure. Individuals with abdominal obesity have more elevated sympathetic neural activation, and visceral adipose tissue has higher expression of angiotensinogen.
Emerging evidence suggest that increased intraabdominal pressure leads to cardiac abnormalities that predispose to heart failure. Several mechanisms by which elevated body mass index increases the risks of heart failure have been proposed including:
Alterations in cardiac loading
Changes in cardiac structure and function
Activation of neurohumoral and inflammatory pathways
Promotion of atherogenic conditions
Predisposition to sleep-disordered breathing.
Interventions: The principal approaches for risk reduction in obese patients should include weight control and physical activity, and control of the associated risk factors (e.g., hypertension, diabetes mellitus, sleep disorders, and metabolic syndrome). Myocardial changes with nonsurgical or surgical weight loss is feasible.
Even minor weight loss is efficacious; a 10% weight reduction ameliorates systolic dysfunction, and weight loss of 8 to 10 kg produces a significant decrease in left ventricular dimensions, mass index, and improves diastolic function. Substantial weight loss reduces left ventricular wall thickness and volume, filling pressure, and improves diastolic measures and systolic function.
The hemodynamic benefits of weight reduction are important and further improve ventricular structure and function related to improved ventricular loading conditions. Although many metabolic and neurohumoral interventions have been implicated in animal models, the roles of the renin-angiotensin-aldosterone system antagonists, lipid-lowering therapy, and insulin-sensitizing drugs in obese humans need further study.
IV. Management of Co-Morbidities
Hypertension is prevalent in the majority of individuals who develop heart failure. Systolic blood pressure increases with age as does the prevalence of hypertension; by 75 years, almost all hypertensive individuals have isolated systolic hypertension.
Diastolic hypertension is more prevalent in individuals below 50 years. Diastolic blood pressure is a potent risk factor till age 50, and thereafter systolic blood pressure becomes more important. Controlling systolic hypertension reduces heart failure rates.
The population attributable risk of hypertension for heart failure is reported to be 39% in men and 59% in women by the Framingham investigators, whereas population attributable risk of uncontrolled blood pressure in the elderly was reported to be 21.3% in whites to 30.1% in blacks in the Health, Aging, and Body Composition Study.
This risk increases in a continuous fashion with the increase in blood pressure. The lifetime risk for heart failure doubles in subjects with blood pressure more than 160/100.
The progression from hypertension to structural changes and systolic and diastolic ventricular dysfunction is well known. Increases in afterload, ventricular mass, and wall stress accompanied by abnormal diastolic filling properties are common.
Increased peripheral vascular resistance places a greater burden leading to an increase in myocardial muscle mass. The development of hypertrophy is associated with progressive changes in the myocytes and an abnormal accumulation of collagen leading to diastolic dysfunction and myocardial stiffness.
The disproportionately increased left ventricular mass leads to inadequate microvasculature to perfuse the hypertrophied myocardium resulting in subendocardial hypoperfusion and ischemia. Hypertension also increases myocardial oxygen demand and is related to endothelial dysfunction, oxidative stress, and development of atherosclerosis.
Abnormalities in the neurohormonal activation, and water and electrolyte balance also play a central role. The renin-angiotensin-aldosterone system activity increases during hypertrophy and heart failure.
Angiotensin II is an important initiator of extracellular matrix remodeling, which contributes to the pathogenesis of atherosclerosis and cardiac hypertrophy. The heightened sympathetic nervous system predisposes to vasoconstriction, sodium retention, and ventricular hypertrophy, and results in myocyte hypertrophy, increased apoptosis of cardiomyocytes, and deficits in cardiomyocyte contractility.
Intervention: The placebo-controlled trials demonstrate the benefit of antihypertensive therapy in reducing the incidence of heart failure. Systolic Hypertension in the Elderly Program (SHEP) demonstrated that antihypertensive treatment when compared to the placebo exerted a strong protective effect, while a meta-analysis of 12 hypertension trials that included the development of heart failure and 4 that included the incidence of left ventricular hypertrophy as endpoints, demonstrated significant benefits. The incidence of left ventricular hypertrophy was decreased by 35% and the incidence of heart failure was reduced by 52% compared to placebo subjects.
Diuretics: Thiazides have been effective in preventing cardiovascular complications of hypertension. Secondary outcomes of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial reported a higher rate of incident heart failure with amlodipine (relative risk of 1.35) and a nonsignificantly increase with lisinopril (relative risk of 1.09) compared with chlorthalidone.
Conversely, the Second Australian National Blood Pressure trial reported better outcomes with a regimen that was initiated with an angiotensin converting enzyme inhibitor compared with a diuretic. Diuretics are at least as good as other classes of drugs and also enhance the antihypertensive efficacy of multidrug regimens. The Joint National Commission 7 recommended that in the absence of any other compelling indications, thiazide diuretics should be used as initial therapy for hypertension.
Renin-angiotensin system modulators: Meta-analysis of trials that measured left ventricular mass show that the greatest reduction was achieved with angiotensin receptor blockers. These agents along with calcium channel blockers and angiotensin converting enzyme inhibitors were more effective in reducing left ventricular mass than beta-blockers.
Both irbesartan- and losartan-based regimens have been shown to reduce left ventricular mass more than atenolol-based treatments, and candesartan had similar efficacy with enalapril. These data suggests that antihypertensive agents targeting the renin-angiotensin system are effective in regression of left ventricular hypertrophy and angiotensin receptor blockers are at least as effective as angiotensin-converting enzyme inhibitors. A recent meta-analysis on renin-angiotensin system inhibition showed that these agents reduce the risk for heart failure by 19% compared with calcium channel blockers.
Angiotensin-receptor/neprilysin inhibitor (ARNI):
Renin Angiotensin Aldosterone System-Neprilysin combination inhibitors, also called ARNi, available now as valsartan/sacubitril (LCZ696)(Entresto®). Sacubitril is an inhibitor of neutral endopeptidase (NEP) which degrades vasoactive peptides like ANP and BNP.
ARNi has recently been approved for patients with symptomatic HFrEF and is intended to be substituted for ACE inhibitors or ARBs, though not for prevention, but in the treatment of heart failure. According to the recent AHA/ACC/HFSA guidelines, ARNi can be used in patients with chronic symptomatic HFrEF New York Heart Association (NYHA) class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNi is recommended to further reduce morbidity and mortality. Use of an ARNI is associated with hypotension and a low-frequency incidence of angioedema. ARNi should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor and in patients with angioedema. Clinical experience with ARNi will provide further information about the optimal titration and tolerability of ARNi, particularly with regard to blood pressure, adjustment of concomitant HF medications, and the rare complication of angioedema.
Beta-blockers: Beta-blockers are effective in lowering blood pressure but these medications are less effective in preventing hypertension complications, including coronary artery and cardiovascular disease, and all-cause mortality or in reducing left ventricular mass. However, a recent meta-analysis suggested that beta-blockers are efficacious for primary prevention of heart failure in hypertension. However, the 19% increased risk for stroke in the elderly associated with beta-blocker use in the same analysis tempers the enthusiasm to use them as first line agents for heart failure prevention in hypertension.
Calcium channel blockers: There are limited data on the effects of calcium antagonists on left ventricular mass or incident heart failure. A meta-analysis suggested that treatment with calcium channel blockers is less effective for reducing heart failure, and the effect of this class of medications on reducing left ventricular mass was similar to that of renin-angiotensin system inhibition.
Target goals of therapy: Systolic and diastolic blood pressure (SBP/DBP) targets are <140/90 mm Hg except for patients with diabetes or renal disease where the goal is <130/80 mm Hg. According to Eighth Joint National Committee (JNC8) group recommendations, it is suggested to target older patients with age > 60 years with a goal of 150/90 mm Hg and younger patients with age <60 years to goal target of 140 mm Hg. Since most patients with hypertension, especially those over 50, will reach the diastolic blood pressure goal once systolic blood pressure is at goal, the primary focus is therefore on systolic blood pressure. Recent data show that effective blood pressure control can be achieved in most patients, but the majority will require two or more medications. Also, data from a randomized trial evaluating the effect of usual versus tight control of systolic blood pressure (<130 mm Hg) in non-diabetic hypertensive individuals with left ventricular hypertrophy demonstrated additional benefit with tighter control. In particular, left ventricular hypertrophy was less frequent but also the composite outcome of all-cause mortality, cardiovascular events, and heart failure was lower in the tight control group.
Data from a recent trial- Systolic Blood Pressure Intervention Trial (SPRINT) show that non-diabetic patients at increased cardiovascular risk, targeting SBP of less than 120 mm Hg vs. the guideline-recommended goal of less than 140 mm Hg, is associated with lower rates of cardiovascular events and all-cause mortality. SPRINT trial was stopped earlier by the data safety monitoring board due to favourable outcomes. The results showed 25% lower relative risk of the primary composite end point (myocardial infarction, acute coronary syndrome, stroke, HF, and cardiovascular death) in less than 120 mm Hg SBP target group vs. the group with less than 140 mm Hg as target SBP. Furthermore, 43% lower risk in cardiovascular deaths and 27% lower risk in all-cause mortality was observed in lower SBP target group, however, there was higher rate of adverse events like, syncope, hypotension and acute kidney injury in the lower blood pressure target group. In particular, the risk of development of HF was reduced significantly (OR 0.62, 95%CI 0.45-0.84, p=0.002). Hence, in light of the current data demonstrating benefits with tighter blood pressure control, the current blood pressure target guideline recommendations are being re-evaluated.
Coronary heart disease
Coronary heart disease predisposing to heart failure risk in both men and women, with reported population attributable risks ranging from 62% in men to 56% in women by the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study and from 23.9% in whites to 29.5% in blacks as reported in the Health, Aging, and Body Composition Study.
Acute Myocardial Infarction: Acute myocardial infarction leads to a cascade of events that promote left ventricular remodeling. Acute loss of myocardial cells results in an increase in loading conditions on the remaining myocardium leading to remodeling involving the infarcted border zone and the noninfarcted myocardium.
Intracellular signaling changes include dilatation, hypertrophy, formation of a collagen scar, neurohormonal and cytokine activation, and oxidative stress. Ventricular remodeling may continue for weeks or months until the distending forces are counterbalanced by the tensile strength of the collagen scar, determining the size, location, and transmurality of the infarct, the extent of myocardial stunning, ventricular loading conditions, and local trophic factors.
Although contemporary treatment attenuates remodeling, there is a large heterogeneity in the response. Remodeling over time becomes deleterious leading to adverse structural and hemodynamic changes leading to heart failure. Reperfusion therapy helps prevent infarct progression; however, it is associated with generation of reactive oxygen species, calcium overload-induced myocardial contracture, and local inflammatory and oxidant response to reperfusion. Thus reperfusion injury is a possible target for interventions to reduce myocardial damage.
Chronic Coronary Artery Disease: Ischemia caused by coronary disease can increase neurohormonal activation (e.g., norepinephrine and endothelin that results in myocardial apoptosis, fibrosis, and susceptibility to ventricular arrhythmias). Ischemia contributes to the progression of systolic dysfunction even in the absence of a known infarction.
Chronic ischemia can result in hibernation or stunning with progressive decline in ventricular function. Hibernation represents a balance between perfusion and tissue viability that cannot be maintained indefinitely, and necrosis will eventually occur if flow is not increased.
Most patients with heart failure resulting from an ischemic origin have a substantial volume of myocardium that fails to contract because it is stunned or hibernating rather than scarred. In addition, endothelial dysfunction, an inherent component of the pathophysiology of atherosclerosis, could directly affect ventricular function.
Ischemic mitral regurgitation, caused by changes in ventricular structure and function, increases left ventricular preload, leading finally to alteration of left ventricle geometry and deterioration of its function. Moreover, myocardial ischemia induces diastolic dysfunction.
Diastolic dysfunction during ischemia precedes and takes longer to recover from than systolic dysfunction. Left ventricular diastolic dysfunction is present in the early phases of myocardial infarction, and it is associated with the development of heart failure and cardiac death; several studies have documented recovery of diastolic function following reperfusion therapy.
Interventions: Prevention of coronary heart disease and ischemic events is key to maintaining functional myocyte; however, in patients with established coronary disease, an aggressive management can reduce heart failure risk. A number of medications and procedures can prevent development of symptomatic heart failure in coronary disease.
The combination of medications along with therapeutic lifestyle changes as recommended in the American Heart Association/American College of Cardiology secondary prevention guidelines should be applied aggressively in all patients to reduce risk of heart failure.
Revascularization: Percutaneous or surgical interventions, or pharmacologic revascularization of the infarct-related artery, reduces the size of the acute infarct and prevents subsequent heart failure if performed early for myocardial salvage. In addition, the “open artery hypothesis” proposes that late reperfusion, beyond the window for myocardial salvage, also reduces left ventricular remodeling. Even after successful early revascularization, older patients are at higher risk for heart failure compared with their younger counterparts.
Angiotensin-converting enzyme inhibitors: ACE inhibitors have favorable properties in reducing left ventricular stress and progression of ventricle enlargement. In the third Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) trial, early lisinopril therapy after acute infarction reduced mortality and left ventricular dysfunction in addition to therapy with aspirin, thrombolytics, and beta-adrenergic blocking agents.
Similar findings were demonstrated in the Survival of Myocardial Infarction Long-Term Evaluation trial with zofenopril. The Heart Outcomes Prevention Evaluation study demonstrated a 23% reduction in risk for heart failure by ramipril in individuals with established vascular disease, expanding the indication for ACE inhibitor therapy to all patients with documented coronary disease, or presumed coronary disease based on the presence of other atherosclerotic vascular disease or diabetes.
The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) showed similar data with perindopril. In the Survival and Ventricular Enlargement (SAVE) trial that enrolled patients with asymptomatic left ventricular dysfunction, captopril lead to a 22% reduction in the risk of heart failure.
Even when these evidence-based pharmacotherapies are instituted, the prognosis of advanced heart failure is dismal. This is best shown in the medical management arm of the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial. This trial randomized patients with chronic systolic heart failure who were ineligible for transplantation to a pulsatile left ventricular assist device or optimum medical therapy. The overall survival of the medical arm at 1 and 2 years was 25% and 8%, respectively, with a median survival of only 150 days. The majority of patients within the medical therapy group died of progressive left ventricular dysfunction (93%) despite frequent inotrope use, with few patients experiencing ventricular arrhythmias.
Angiotensin-receptor blockers: Angiotensin-receptor blockers are at least equally effective as ACE inhibitors in reducing mortality in patients with myocardial infarction complicated by left ventricular dysfunction or heart failure. Data on patients with atherosclerotic diseases but without heart failure is not uniform.
Since the overall evidence for the effectiveness of angiotensin-receptor blockers on prevention and attenuation of postmyocardial infarction left ventricular remodeling is weaker compared with ACE inhibitors, they may not be used as first-line therapy but limited to those individuals who do not tolerate angiotensin-converting enzyme inhibitors.
Beta-blockers: Beta-blockers have been proven to be beneficial after acute myocardial infarction. Long-term beta-blocker use is recommended for secondary prevention in patients at highest risk (e.g., those with low ejection fraction or heart failure).
The echocardiographic substudy of Carvedilol Post Infarction Survival Control in Left Ventricular Dysfunction (CAPRICORN) demonstrated a beneficial effect of carvedilol on left ventricular remodeling in patients with left ventricular dysfunction after infarction over that of ACE inhibitors. The Reversal of Ventricular Remodeling with Toprol-XL (REVERT) trial showed that beta-blocker use in asymptomatic left ventricular dysfunction prevents development of heart failure.
Aldosterone antagonists: High aldosterone in patients with myocardial infarction leads to ventricular remodeling. Spironolactone combined with ACE inhibitors reduced left ventricle remodeling after acute myocardial infarction better than ACE inhibitors alone in one study. Aldosterone antagonists are recommended in myocardial infarction complicated by left ventricular dysfunction, based on the beneficial effect on mortality and cardiovascular hospitalizations seen in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS).
In Randomized Aldosterone Evaluation Study (RALES) in heart failure patients, spironolactone significantly decreased the risk of all-cause mortality and, in particular, death from worsening heart failure and sudden cardiac death. All-cause mortality fell from 46% to 35%. The extent of benefit of spironolactone was comparable to early observations made with ACE inhibitors in severe heart failure, but in this case it was additive to the ACE drug class. Using low doses of spironolactone, serious hyperkalemia or azotemia was rare; the only significant problem was gynecomastia or breast pain in 10% of treated patients, most commonly reported by men.
Antiplatelet agents: Aspirin in patients with established vascular disease has been demonstrated to reduce risk for cardiovascular events and heart failure, and is recommended after acute myocardial infarction, and should continue indefinitely if no contraindications exist.
Statins: Statins are of proven benefit in patients with coronary disease; however, their benefit in left ventricular dysfunction remains under investigation. Treatment with a statin before percutaneous coronary intervention is associated with lower levels of creatine kinase elevation.
Chronic statin therapy before an acute event is associated with improved perfusion and reduced myocardial necrosis. Kjekshus et al showed a 11% lower risk of heart failure in patients with stable coronary disease treated with statins. Similar trends were also demonstrated in other studies.
Novel approaches: Several novel mechanistic insights into myocyte function, and repair and remodeling, may lead to development of newer therapies in the future, including those targeted at nitric oxide-cGMP signaling, oxidative stress, inflammation, matrix-metalloproteinase inhibition, and stem cell therapy.
Diabetes mellitus is an independent risk factor for heart failure in all age groups. The relative risk for heart failure in patients with diabetes mellitus ranges from 1.3 to 2.7, increasing to 4 in patients younger than 65 years and 11 in those younger than 45.
Comorbidities associated with heart failure, including obesity, hypertension, and coronary artery disease, are highly prevalent among individuals with diabetes mellitus. Insulin resistance itself may produce abnormalities in cardiac structure and function. Hence, heart failure and diabetes are linked and each condition increases the risk for the other resulting in poorer prognosis than with either condition alone.
However, insulin resistance and hyperglycemia are the central pathophysiological mechanisms that may lead to diabetic cardiomayopathy. All indicators of insulin resistance, for example HbA1c, fasting glucose, and insulin levels have been associated with a risk of developing heart failure. Patients with insulin resistance exhibit endothelial dysfunction and a pro-inflammatory state, which contribute to ventricular dysfunction, even before the development of overt diabetes mellitus. Left ventricular hypertrophy and dysfunction are also correlated with insulin resistance, and hyperinsulinemia has been associated with sympathetic nervous system activation.
Mechanisms proposed for the development of “diabetic cardiomyopathy” include;
Microangiopathy and endothelial dysfunction
Autonomic neuropathy, which causes impaired coronary vasodilatory response to sympathetic stimulation and modulates the contractility of cardiac myocytes
Metabolic derangements, such as reduced glucose and lactate metabolism and enhanced fatty acid metabolism, result in lipid accumulation in the myocardium promoting lipotoxicity
Abnormalities in ion channels, such as calcium and potassium channels, and function of sodium-calcium exchangers, SERCA2a, calcium binding proteins, and the mitochondrial calcium uniporter
Upregulation of the renin-angiotensin system
Increased oxidative stress
Increased glycation of interstitial proteins
Activation of protein kinase C
Empagliflozin-A novel agent:
In a recent study- Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) on patients with type 2 diabetes, Empagliflozin, a sodium/glucose cotransporter 2 (SGLT2) inhibitor, significantly reduced, cardiovascular mortality by 38% (3.7% in treatment arm vs. 5.9% in placebo: HR=0.62, 95% CI:0.49-0.77m P<0.001) and over-all-mortality by 32% (5.7% in treatment arm vs. 8.3% in placebo: HR=0.68, 95% CI:0.57-0.82, P<0.001). However, Empagliflozin did not reduce the rates of non-fatal myocardial infarction or non-fatal stroke, significantly. The data suggest that 39 patients would need to be treated with Empagliflozin to prevent 1 death (all-cause mortality) over three years. There was a 35% reduction in the risk for HF hospitalization (OR 0.65, 95% CI 0.50-0.85, p=0.002). Hence, this drug may have impact on reducing the development and progression of heart failure. It would be interesting to see the effects of this agent in patients without diabetes.
These results are important as the recent data so far from other newer drugs like incretins and dipeptidyl peptidase-4 (DDP-4) have not shown favourable impact on cardiovascular events.
Insulin: Randomized trials indicate that insulin use in ACC-AHA stage A heart failure does not appear to increase the risk for heart failure, and insulin use in stage B heart failure does not negatively impact mortality. Whether insulin use specifically reduces the risk for heart failure is not known.
Sulfonylureas: Sulfonylurea therapy does not increase the risk of heart failure compared with other oral antidiabetic agents, although the ADOPT (A Diabetes Outcome Progression Trial) was not powered to detect significant differences.
Metformin: The heart failure risk among patients treated with metformin compared with other oral medications was reported in ADOPT and the findings were similar as for sulfonylureas.
Thiazolidinediones: The hypothesis that therapies that correct abnormal substrate metabolism will translate to lower incidence of heart failure appears promising; however, the available data argue against this hypothesis. Although treatment with thiazolidinediones increased myocardial glucose uptake in patients with underlying coronary disease, and myocardial glucose uptake seems to be positively correlated with left ventricular function, the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study has indicated that thiazolidinedione use is associated with a small but clinically relevant increased risk of heart failure in patients with ACC-AHA stage A or stage B status.
Pioglitazone: In a study in patients with type 2 diabetes and systolic heart failure, pioglitazone when used with glyburide, was associated with increase in mortality, however, it significantly reduced the development of myocardial infarctions and strokes.
Other agents: There are limited data regarding other antidiabetic therapies for heart failure risk, except for the alpha-glucosidase inhibitor acarbose; its impact on cardiovascular disease outcomes was evaluated in the STOP-Noninsulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial. Although the study was not powered to evaluate the impact of acarbose on development of heart failure, the available data suggests that this agent may decrease the risk of myocardial infarction and subsequent risk of heart failure.
Glycemic control: Evidence suggests that managing hyperglycemia aggressively in type 2 diabetes mellitus does not reduce progression of heart failure. In the United Kingdom Prospective Diabetes Study (UKPDS) 33, no significant reduction in the development of heart failure was demonstrated with intensive blood glucose control.
Blood pressure control: Because hypertension increases the risk of heart failure in diabetes mellitus, aggressive blood pressure management is essential in this population. In UKPDS 38, tight blood pressure control with either the ACE inhibitor or beta-blocker significantly reduced the risk of cardiovascular events and diabetes-related mortality, including a 56% reduction in the risk for heart failure. Notably, the target blood pressure level was <150/85 mm Hg in that study, whereas the Seventh Report of the Joint National Commission on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) recommended more aggressive blood pressure control (target blood pressure <130/80 mm Hg) in patients with diabetes.
Targeting mechanisms for diabetic cardiomyopathy: The mechanisms leading to diabetic cardiomyopathy are complex. Medications like ACE inhibitors and beta-blockers benefit patients with diabetes mellitus and prevent complications including heart failure.
The Heart Outcomes Prevention Evaluation (HOPE) trial, and the Microalbuminuria, Cardiovascular, and Renal Outcomes (MICRO-HOPE), a substudy of HOPE, have shown that treatment with ACE inhibitor reduces the risk for heart failure by 23% and 20%, respectively, in a population of ACC-AHA stage A or B patients, whereas the extension of HOPE study revealed that the benefit of an ACE inhibitor for heart failure prevention is sustained over time.
Likewise, the Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study and the Losartan Intervention for Endpoint Reductions in Hypertension (LIFE) study showed a 32% and 41% reduction in the frequency of hospitalization for heart failure, respectively. A recent meta-analysis evaluating the beneficial effects of the agents that inhibit the renin-angiotensin system on reducing the risk for heart failure, showed that their favorable effect was beyond blood pressure control and the risk was 19% lower than calcium channel blockers.
Obstructive sleep apnea is characterized by abnormal collapse of the pharyngeal airway during sleep, causing repetitive arousals. Obesity is a major risk factor, partly because layering of fat adjacent to the pharynx narrows its lumen.
The Wisconsin Sleep Cohort Study, a large population-based study, reported that obstructive sleep apnea affects approximately 15% of men and 5% of women between the ages of 30 and 60 years when sleep apnea is defined as an apnea-hypopnea index of ≥ 10 events per hour. Other studies reported similar findings or a higher prevalence.
Obstructive sleep apnea is related with hypertension coronary disease and diabetes mellitus. In addition, obstructive sleep apnea induces left ventricular dysfunction independently of hypertension.
In the Sleep Heart Health Study, obstructive sleep apnea was associated with a 2.38 relative risk of heart failure when the apnea-hypopnea index was ≥11 events per hour. Obstructive sleep apnea may lead to heart failure through (1) development and worsening of comorbidities, and (2) neurohormonal abnormalities and mechanical modifications.
In obstructive sleep apnea, negative intrathoracic pressure generated by the inspiratory effort during obstructed breathing increases left ventricular afterload, changes venous return affecting preload and stroke volume, and increases the cardiac muscle work. The sympathetic activation due to hypoxia increases blood pressure and heart rate, increasing cardiac afterload, and reduces myocardial perfusion. Increased venous return accompanied by acute hypoxic pulmonary vasoconstriction, increases right ventricular volume and pressure, and also may compromise left ventricular filling.
Intervention: Sleep apnea treatment using devices that provide continuous positive airway pressure has been shown to improve left ventricular function in patients with established left ventricular dysfunction and reverse functional ventricular abnormalities.
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