March 13th, 2018
Deepa Ramadurai, MD
David Tanaka, MD
University of Colorado Internal Medicine Residency Training Program, Aurora, CO
An 81-year-old African-American man with a history of hypertension, well-controlled type 2 diabetes (hemoglobin A1c 6.0%), and Stage III chronic kidney disease (CKD) presented to primary care clinic with lightheadedness and fatigue over the past two months. He was previously a 3-times-per-week golfer and cared for his grandchildren regularly, activities that were significantly compromised by his new symptoms. He was evaluated once by his prior internist and once by his prior nephrologist since the start of these symptoms. Investigations at these appointments were normal, including orthostatic testing, thyroid function tests, complete blood count, and transthoracic echocardiography. Three months ago, his anti-hypertensives had been up-titrated with the goal of achieving tight blood pressure (BP) control given his history of diabetes and CKD. Current medications included nebivolol, hydralazine, amlodipine, and valsartan. On exam, his BP was 132/64 mmHg, heart rate was 60 beats/minute, and he appeared generally well. Gradual tapering and eventual discontinuation of both nebivolol and hydralazine were pursued with complete resolution of his lightheadedness and fatigue. His BP remained at or below 140/70 mmHg on several follow-up visits in the following one year.
The 2016 National Health and Nutrition Examination Survey (NHANES) measures the prevalence of hypertension among adults aged 20 and older at 33.5% in 2014. Of those with hypertension, the majority are aged 60 years or greater (1). Numerous studies over the past 30 years have attempted to define optimal BP targets. JNC 8 guidelines specify goals on the basis of patient age, ethnicity, presence of diabetes, CKD, and coronary artery disease (1). Age is well known to increase risk for cardiovascular risks, making the decision of a BP target clinically complex in an elderly population that is also more prone to adverse effects of polypharmacy and medication side effects.
The patient in this case met multiple indications for “high-risk hypertension” including African American race, comorbid type 2 diabetes mellitus and CKD. Although JNC 8 guidelines recommend BP targets less than 150 mmHg systolic and 90 mmHg diastolic in persons aged 60 and older, “high-risk” features change the systolic target to less than 140 mmHg, as guided by data from SPRINT (2). Notably, this study excluded patients with diabetes. ACCORD-BP demonstrated no difference in nonfatal myocardial infarction, nonfatal stroke, nor cardiovascular mortality in patients with diabetes with systolic targets <140 mmHg as compared to <120 mmHg, lending conflicting data and leaving room for debate (3). Experts generally recommend lower BP targets regardless for diabetic patients, without a strong backing of high-quality evidence.
We also recognize aggressive BP treatment can be associated with a higher risk for adverse events including hypotension and syncope in the elderly population (4). The presence of adverse effects in limiting daily activities is a relevant reason for discontinuation of anti-hypertensive therapy, as quality of life is compromised. Pill burden or polypharmacy in the elderly population is another reason to consider limiting medications in hopes of improving adherence. HYVET suggested that very elderly patients (≥80 years) with hypertension may safely continue treatment to a goal of 150/90 mmHg as opposed to no treatment at all (4).
In this case, achieving steady state for the new anti-hypertensive regimen coincided with the initiation and worsening of the patient’s fatigue, lightheadedness, and poor exercise tolerance. Based on his risk profile as an African American male with diabetes, the evidence is best for certain classes of anti-hypertensives including thiazide diuretics, modifiers of the renin-angiotensin-aldosterone system, and calcium channel blockers (1). Therefore, emphasis was placed on discontinuing agents not in these classes: hydralazine and nebivolol. Although an aggressive work-up for ischemic heart disease, valvular pathology, or other conditions that might involve invasive diagnostics is often pursued for this constellation of symptoms in a patient with risk factors, polypharmacy is a more common culprit (4).
The debate regarding hypertension guidelines continues. Although numerous studies attempt to address BP targets in general, it is rare that a study recruits an adequately representative population with comorbidities that alter the approach to treating hypertension. The newest guideline data is conflicting, as the American Heart Association definition of hypertension has been liberalized to BP greater than 130/80, resulting an increase the prevalence of hypertension and sheer numbers who need treatment. The American College of Physicians and Association of Family Physicians, however, continue to endorse treatment threshold of 150 mmHg systolic in adults aged 60 and older (5). The latter organizations cite shared decision-making as critical to this process in the aging population. This case is an excellent example of the importance of discussing side effect profile and the impact on quality of life weighed against risk for major cardiovascular events as we individualize care plans for our patients.