Prof. Guido Grassi
Explore here the association between obesity and hypertension and find an updated review of the therapeutic indications and treatment of hypertension and resistant hypertension within this context.
Large scale epidemiological studies have shown that hypertension is two to three times more present in the obese than in lean individuals. Moreover, blood pressure values and body weight are directly related at any age of life. These findings denote a close association between obesity and hypertension (1-2). More specifically, obese individuals with central (or visceral) fat dominant distribution tend to have higher hypertension than those with non-central fat dominant distribution (2).Additionally, obesity appears to be an important cause of difficult-to-treat hypertension and of treatment-resistant or refractory arterial hypertension (1,3).
Resistant hypertension is a clinical state in which a therapeutic plan that has included 1) Attention to lifestyle measures and 2) Prescription of at least three drugs in adequate doses including a diuretic have failed to lower systolic and diastolic blood pressure at goal (1). It is associated with a variety of conditions: 1) Obstructive sleep apnea, cigarette smoking and most importantly 2)The obese state, probably as a result of the peculiar pathophysiological background of obesity-related hypertension (2). Obesity-related hypertension often is accompanied by: 1) Blood volume overload 2) Rennin-angiotensin stimulation with inappropriately high circulating plasma levels of aldosterone 3) Insulin resistant state 4) Stimulation of the sympathetic nervous system and 5) Obstructive sleep apnea syndrome (further complicating the obese state).
Therefore, a cardiovascular and metabolic risk assessment - through evaluation of blood pressure, body weight, body fat and body mass index - revealing both obesity and hypertension must give way to a carefully considered treatment strategy in order to attain adapted, optimal risk reduction.Weight loss may improve hypertension-associated target organ damage independently from blood pressure - for example, weight loss reduces urinary albumin excretion and may favor regression of left ventricular hypertrophy. Interventions based on weight loss should be primary treatment (4-5). The ESH/ESC guidelines 2013 recommend that weight reduction or weight stabilisation should be instituted in overweight patients. Evidence that weight reduction may have a beneficial effect on overall risk and that weight reduction may lower blood pressure are the rationale for this recommendation. Adequate behavioral and expert support are needed to ensure a patient's weight reduction, the guidelines go on to state, however the latest guidelines still do not provide details as to what patients should do to lose weight.
What is recommended in the guidelines, is that a flexible approach taking into consideration 1) associated risk factors, such as presence of the metabolic syndrome, as well as 2) target organ damage or 3) cardiovascular disease is recommended. While many obese hypertensive patients ultimately require antihypertensive medication, here are their needs more specifically addressed. Our current understanding of the mechanisms involved in obesity-associated arterial hypertension are that obesity-associated arterial hypertension comes with volume expansion and increased neurohumoral activation. As such:
Limitations for the use of beta-blockers, however, especially in young obese hypertensive patients without cardiac and renal complications, are their potential negative effects on glucose metabolism and body weight.
Data on how to treat obese patients with resistant arterial hypertension are scarce.
Spironolactone: A recent study suggests that, adding the mineralocorticoid antagonist spironolactone may be useful in these patients (7). In another study, true resistant hypertension patients diagnosed by ambulatory blood pressure monitoring, were treated with spironolactone treatment in doses of 25–100 mg/day. A second ambulatory blood pressure monitoring performed after a median interval of 7 months showed a 16/9 mmHg reduction in blood pressure. Remarkably, higher waist circumference was associated with better response to spironolactone. These findings point to the special role of aldosterone in obesity associated hypertension.
Direct renin inhibition: It may be an effective alternative treatment approach in obese hypertensive patients. However, this medication should be used with caution, particularly in combination with other renin-angiotensin system inhibitors or renal disease (8).
Many of the patients included in these trials were overweight or obese. Renal sympathetic denervation through a novel catheter based approach substantially reduced clinic blood pressure in patients with treatment-resistant arterial hypertension with an overweight or an obese state (3-9). Ambulatory blood pressure values appear to be also reduced by the intervention, although the magnitude of the blood pressure lowering effects appear to be less pronounced compared to effects on clinic blood pressure (3-9). The response may be mediated in part through ablation of renal afferent nerves decreasing centrally generated sympathetic activity.
This treatment requires surgical implantation of an electrical stimulatory device and electrodes located at the level of the carotid sinus. Although promising, renal sympathetic denervation through a novel catheter based approach and electrical stiumation of carotid baroreceptor approaches need in to be tested in large scale clinical trials a near future.
The data discussed in this brief review article addresses the difficulties in achieving blood pressure control in treated obese hypertensive patients. They also underline the need for using combination drug treatment in these patients, along with non pharmacological interventions aimed at reducing body weight. Combination drug treatment based on ace-inhibitors or angiotensin II receptor blockers, anti-aldosterone drugs as well as calcium channel blockers appears mandatory in the obese hypertensive patient, before considering renal denervation or carotid baroreceptor stimulation. Appealing, but still requiring further evaluation, are the initial results obtained with interventions aimed at reducing symapthetic overdrive, such as renal nerve radiofrequency ablation and carotid baroreceptor stimulation.
1. Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 Eur Heart J. 2013;34:2159-219.2. Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment: a position paper of The Obesity Society and the American Society of Hypertension.Landsberg L, Aronne LJ, Beilin LJ, Burke V, Igel LI, Lloyd-Jones D, et al. J Clin Hypertens (Greenwich). 2013;15:14-33.3. Updated ESH position paper on interventional therapy of resistant hypertension. Schmieder RE, Redon J, Grassi G, Kjeldsen SE, Mancia G, Narkiewicz K, et al. Eurointervention 2013;9 (suppl R):R 58-R66.4. Left ventricular mass and function with reduced-fat or reducedcarbohydrate hypocaloric diets in overweight and obese subjects.Haufe S, Utz W, Engeli S, Kast P, Bohnke J, Pofahl M, et al. Hypertension 2012; 59:70-75.5. European Society of Hypertension Working Group on Obesity antihypertensive effects of weight loss: myth or reality?Straznicky N, Grassi G, Esler M, Lambert G, Dixon J, Lambert E, et al. J Hypertens 2010; 28:637-643.6. Management of hypertension in overweight and obese patients: a practical guide for clinicians.Dentali F, Sharma AM, Douketis JD. Curr Hypertens Rep 2005; 7:330-336. 7. Efficacy of spironolactone therapy in patients with true resistant hypertension.de Souza F, Muxfeldt E, Fiszman R, Salles G. Hypertension 2010; 55:147-152.8. Aliskiren-based therapy lowers blood pressure more effectively than hydrochlorothiazide-based therapy in obese patients with hypertension: sub-analysis of a 52-week, randomized, double-blind trial.Schmieder RE, Philipp T, Guerediaga J, Gorostidi M, Bush C, Keefe DL. J Hypertens 2009; 27:1493-1501.9. Novel antihypertensive therapies: renal sympathetic nerve ablation and carotid baroreceptor stimulation.Grassi G, Seravalle G, Brambilla G, Bombelli M, Dell'Oro R, Gronda E, et al. Curr Hypertens Rep 2012; 14:567-572.
Guido GrassiClinica Medica, Ospedale San Gerardo, Monza and University of Milano Bioccca, Milan, Italy.Authors' disclosures: None declared.
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