Obesity and hypertension: It's about more than the numbers

Authors

  • Keith C. Ferdinand

    Corresponding author
    1. Tulane Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, LA 70112, USA
    • Tulane Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, LA 70112, USA
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  • Disclosures: Dr. Ferdinand is a consultant for Roche, Merck, Forest, Takeda, and Astra Zeneca, and has received research grants from Novartis and Daiichi Sankyo. He is an American Society of Hypertension Board of Directors member.

Abstract

Objective:

This editorial comments on the recent Obesity Society and American Society of Hypertension joint position paper, justified by the substantial link between obesity and hypertension (HTN).

Design and Methods:

The editorial reviews the expert opinions. Other relevant clinical research is highlighted, such as an obesity paradox. Evidence-based lifestyle changes, drugs, and behavorial modification and newer agents are highlighted.

Results:

Areas of controversy are noted. Despite the importance of renin angiotensin system blockage, future federal guidelines may maintain thiazides as first choice, even with metabolic syndrome (MetS) and diabetes (DM). Chlorthalidone, 12.5-25 mg, has shown cardiovascular benefit, including with MetS and DM.

Conclusion:

The conclusion calls for more research. However, the identification and elimination of racial/ethnic disparities should be addressed more explicitly. To better understand the obesity–hypertension linkage, curtail costs, and decrease premature disease and death, this excellent position paper is essential.

Obesity and Hypertension: It's About More Than the Numbers

The growing obesity epidemic is a major source of unsustainable health costs, and morbidity and mortality because of hypertension (HTN), type 2 diabetes mellitus (DM), dyslipidemia, certain cancers, and major cardiovascular diseases (CVD). The substantial obesity–HTN link clearly justifies the recent Obesity Society and American Society of Hypertension joint position paper on obesity-related HTN (1). Comprehensive, up-to-date expert opinion documents are essential to inform clinicians, guide understanding, and prevent and control these common, but potentially deadly, conditions. Nevertheless, clinicians must recognize limitations in present and future evidence-based reports in guiding exemplary quality care; the wise application of empirical facts requires both information and judgment. The authors of the obesity-related hypertension paper interpreted vast amounts of data to synthesize their recommendations; however, a few specific concerns should be recognized.

First, clinical research reveals an obesity paradox, where overweight/obese patients with HTN, heart failure (HF), coronary heart disease (CHD), and peripheral arterial disease have, perhaps, even a more favorable short- and long-term prognosis. Notably, a large cohort study of 22,576 treated hypertensive patients with known CHD demonstrated all-cause mortality was 30% lower in overweight/obese compared to normal weight patients (2). Moreover, the landmark Systolic

Hypertension in Elderly Program showed decreased stroke and total mortality among overweight compared with lean patients (3). Therefore, although obesity is a powerful risk factor for HTN and left ventricular hypertrophy, obese hypertensive patients may paradoxically have a better prognosis compared with lean patients (4). Similarly, with HF, obese patients may have a better event-free survival (5).

Second, the authors note despite the definite hypertension-related short- and long-term cardiovascular (CV) risk, the link of obesity with short-term CVD events may be more problematic. Consistent evidence demonstrates a decrease in blood pressure (BP) with weight loss, and the article appropriately places strong emphasis on lifestyle changes in the management of obesity-related HTN, including diet, physical activity, and behavioral modification. The recent Look AHEAD (Action for Health in Diabetes) study, including a large diverse cohort (n = 5,145, 37% from ethnic/racial minorities), bolsters the strong association of weight loss magnitude (P < 0.0001) with improvements in CV risk factors, including elevated BP. Compared with weight-stable participants, those who lost 5-<10% body weight had increased odds of achieving a 5-mm Hg decrease in diastolic BP (1.48 [1.20-1.82]), or in systolic BP (1.56 [1.27-1.91]), with even greater benefits in larger weight losses (6).

Considering the gap between weight loss amounts achievable by a primary care physician treating an individual patient versus weight loss in academic medical centers with intensive lifestyle programs, such as Look AHEAD delivered by a team of trained interventionists, the future challenge will be to develop reproducible models that can be more widely disseminated. Although past anti-obesity drugs have had either limited efficacy or significant toxicity, newer, safe agents, often in combination, are welcomed additions to achieving often previously unsuccessful weight loss attempts, reinforcing appetite reduction and satiety promotion.

Finally, the article expresses some potentially controversial concepts related to HTN therapy. The rennin–angiotensin–aldosterone system (RAAS) is appropriately highlighted for special significance in obese patients, making the case to consider angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) as more reasonable firstline agents. However, hypertension specialists continue to have robust debates on which agents to utilize for which patients. The authors' emphasis on the adverse effects of thiazides, and as possibly less desirable firstline in obese patients prone to the metabolic syndrome (MetS) and type 2 DM, may not be in concert with future U.S. federally sponsored guidelines, which may maintain first choice thiazides, even with MetS and DM. Moreover, suggesting “low-dose” thiazides, 12.5-25 mg of hydrochlorothiazide (HCTZ) or an equivalent agent is based on limited evidence. In the largest antihypertensive trial ever, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), chlorthalidone 12.5 to 25 mg—certainly not equivalent to “low-dose” HCTZ—showed CV benefits, including with MetS and DM. Furthermore, the proposed alternative loop diuretics, with little or no randomized trial data, are not as useful in BP reduction and CV outcomes as adequately dosed thiazides.

Although an Australian trial is accented for slightly better outcomes in hypertensive white men (half of 6,083 subjects, average BMI 27.4) with an ACE inhibitor versus diuretic-based regimen, ALLHAT in a larger, heterogeneous North American population, showed no such evidence in either sex, for superiority of treatment regimens with a calcium channel blocker or an ACE inhibitor compared with chlorthalidone in patients with DM (n = 13,101), impaired fasting glycemia (IFG, n = 1,399), or normoglycemia (NG, n = 17,012). Average BMI was higher with DM (31.1) or IFG (30.5) compared with those with NG (28.7) (7, 8). Moreover, among 7,327 Black ALLHAT participants with MetS, mean BMI (SD) 33.3 (6.5), the systolic/diastolic BPs were 3/1 mm Hg higher with randomization to lisinopril-based therapy (P < 0.001 and 0.03, respectively) compared with chlorthalidone, associated with higher combined CHD (HR = 1.19, 1.01–1.40), combined CVD (HR = 1.24, 1.09–1.40), stroke (HR = 1.37, 1.07–1.76), HF (RR = 1.49, 1.17–1.90), and end-stage renal disease (HR = 1.70, 1.13–2.55). Moreover, non-Blacks with lisinopril and MetS had higher rates of combined CVD (HR = 1.10, 1.02–1.19) and HF (RR = 1.20, 1.01–1.41) (9). The ALLHAT investigators concluded thiazides should be first-step hypertensive agents in most patients, including with DM or IFG (8, 9). Nevertheless, in most obese patients, especially with stage 2 HTN, combination therapy will be necessary to secure the benefits of RAAS blockage. In the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, N = 11,482, combination therapy either adding HCTZ or amlodipine to benazepril appear effective for decreasing both BP and CV events in high-risk patients with HTN, although the thiazide/ACE inhibitor combination provided less CV protection in normal weight than obese patients (10).

The position paper's conclusion appropriately calls for more research. Although mentioned, identification and elimination of racial/ethnic disparities in HTN, DM, and cardiometabolic risk should be even more explicitly addressed. Nevertheless, overall, as a guide to better understand the obesity–hypertension linkage, curtail healthcare costs and decrease premature disease and death, this excellent report is essential.

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