A 65-year-old woman comes to the office due to a 2-month history of shortness of breath and lower extremity edema. The patient reports no chest pain, palpitations, or syncope. She takes chlorthalidone and lisinopril for chronic hypertension. The patient has a sedentary lifestyle. She drinks 1-2 glasses of wine with dinner most days of the week. Blood pressure is 145/94 mm Hg and pulse is 80/min. BMI is 40 kg/m². Estimated jugular venous pressure is 9 cm H₂O. Cardiac examination reveals a regular rate and rhythm with no murmurs. Crackles are heard bilaterally in the lung bases. Bilateral pitting pedal edema is present. Chest x-ray shows a normal cardiac silhouette with pulmonary vascular congestion. Echocardiogram demonstrates left atrial enlargement, mild concentric left ventricular (LV) hypertrophy, mild mitral regurgitation, and no pericardial effusion. LV ejection fraction is 65% and there are no wall motion abnormalities. Serum creatinine is 0.8 mg/dL. Serum lipid studies show a total cholesterol of 208 mg/dL, HDL cholesterol of 35 mg/dL, and LDL cholesterol of 136 mg/dL. Which of the following is the strongest predisposing factor to this patient's current condition?

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11ec25c8_d0a9_d2cb_bc81_47c8b2c6c97d_MD0003_00 This patient has clinical signs and symptoms of decompensated heart failure (eg, dyspnea, pulmonary and lower extremity edema, jugular venous distension). Heart failure is characterized by reduced cardiac output due to impaired contractility (ie, systolic dysfunction) and/or relaxation (ie, diastolic dysfunction). This patient's normal ejection fraction on echocardiogram is indicative of heart failure with preserved ejection fraction (HFpEF). HFpEF is the result of progressive cardiac remodeling that is induced by both systemic and local factors affecting cardiac myocytes and the surrounding interstitium. Chronic hypertension results in elevated systemic vascular resistance, which exerts a hydraulic stress on the left ventricle (LV) by increasing afterload. This stress on the LV initiates concentric hypertrophy of cardiac sarcomeres, which is perpetuated by systemic inflammation commonly seen in individuals who are sedentary and/or obese (eg, cytokines released from adipocytes). concentric hypertrophy Systemic inflammation predisposes patients to microvascular ischemia, which leads to further sarcomeric hypertrophy and collagen deposition in the interstitial space. The result of these changes is stiffening of the LV, impaired diastolic filling (decreased compliance), and heart failure (reduced cardiac output). (Choices A and F) Heavy alcohol use and certain viruses (eg, coxsackie) can occasionally cause dilated cardiomyopathy, which would present as heart failure with reduced ejection fraction (HFrEF) (ie, systolic dysfunction) rather than HFpEF. (Choice B) Hypertrophic cardiomyopathy, caused by a plethora of hereditary mutations in various sarcomere genes, can also present with concentric hypertrophy and diastolic dysfunction. However, hypertrophic changes typically occur in the septum (rather than the entire myocardium) and can be easily visualized on echocardiogram. (Choice C) Hypercholesterolemia is a significant risk factor for developing coronary artery disease (CAD). Although CAD is common in patients with HFpEF, it is not as significant a contributor to HFpEF as hypertension, obesity, or a sedentary lifestyle. Myocardial ischemia due to CAD most commonly manifests as HFrEF. (Choice E) Severe regurgitant valvular heart disease (eg, mitral regurgitation, aortic regurgitation) is a common cause of HFrEF, but does not typically contribute to HFpEF; in addition, this patient only has mild (rather than severe) mitral regurgitation. Aortic stenosis can contribute to the concentric hypertrophy that underlies HFpEF, but it is unlikely in this patient with no murmurs. Educational objective: Heart failure with preserved ejection fraction is characterized by progressive stiffening of the left ventricle resulting in impaired diastolic filling and reduced cardiac output. In addition to chronic hypertension, systemic inflammation from a sedentary lifestyle and/or obesity plays a significant role. References: Sedentary lifestyle and the risk for HFpEF: are "huff-puff health clubs" the answer? (http://www.ncbi.nlm.nih.gov/pubmed/28254176)

A 65-Year-Old Woman Comes to the Office Due to a 2-Month