The obese state, which affects more than 20% of the adult population worldwide with prevalence trends that have steadily increased through the years, is a major risk factor for cardiovascular disease as well as for the development of hypertension.
This paper will review the pathophysiologic profile of the condition defined as “obesity-related hypertension”. It will also discuss the pharmacologic as well as the non-pharmacologic strategies to lower blood pressure values in this condition, thereby providing indications on how to effectively reduce the elevated cardiovascular risk of the obese hypertensive patients.
Pathophysiology of obesity-related hypertension
Epidemiological surveys performed in different countries around the world strongly support the notion that body weight, body mass index and blood pressure values are linked together by a close and direct relationship (1).
Evidence has been provided that, both in experimental animals and in humans, an increase in body fat (particularly in the abdominal area) triggers an increase in blood pressure values, which can be reversed by interventions capable of reducing body weight (2).
Hypotheses explaining the occurrence of a high blood pressure state in the obese
Over time, several hypotheses have been advanced for explaining the occurrence of a high blood pressure state in the obese population. It was initially thought that the blood pressure increase was dependent of so-called “haemodynamic factors”, i.e. on the hypervolemic state as well as on the increase in cardiac output characterising body weight gain - at least in the earlier phases of the disease (2).
As years have passed, other hypotheses have linked the development of obesity-related hypertension to metabolic, neurohumoral, renal and endothelial abnormalities.
Although we are still waiting for an “unifying theory”, some pathophysiological features have been identified as the “driving forces” of the disease (2,3).
1) renin-angiotensin activation,
2) stimulation of the sympathetic nervous system and
3) early occurrence of a renal dysfunction leading to glomerular hypofiltration, sodium retention as well as to microalbuminuria.
All these mechanisms may trigger a blood pressure increase via direct as well as indirect mechanisms. This being the case because 1) angiotensin II increases peripheral vascular resistance and exerts powerful central pressor effects, 2) adrenergic drive promotes peripheral and renal vasoconstriction and, trough these mechanisms, elicits sodium retention and 3) renal impairment favours an elevation in blood pressure levels (2-3).
Other pathophysiological mechanisms, however, participate in the phenomenon. These include, for example, the insulin resistance state (and the related hyperinsulinemia) which is common in obesity and exerts sympathostimulatory and vasoconstrictive effects (4). They also include the increase in circulating levels of leptin, i.e. the adipocyte-derived hormone which may display pressor and sympathoexcitatory effects (5). A further mechanism is represented with the high prevalence in the obese state of the sleep apnea syndrome which, via a chemoreflex dysfunction, may further potentiate the already elevated adrenergic cardiovascular drive (3).
Non pharmacological interventions aimed at lowering body weight, such as dietary restrictions in caloric intake and/or measures to improve physical fitness, have been shown to
1) decrease blood pressure,
2) favorably modify the obesity-related increase in metabolic risk factors and
3) improve, or even restore to normal the metabolic, sympathetic, neurohumoral and endothelial dysfunctions (6).
However, long term maintenance of a reduced body weight is a difficult goal to achieve, making it necessary to base treatment strategies on correction of cardiovascular risk factors, including the hypertensive state.
Which blood pressure lowering strategy should be used?
Which blood pressure lowering strategy should be indicated in obesity-related hypertension remains a matter of debate (7) for the following reasons:
1) there are currently no therapeutic recommendations for the disease and
2) there are very few investigations specifically addressing this issue in obese populations.
From the results of two of them - the Treatment in Obese Patients with Hypertension (TROPHY, 8) and the Candesartan Role on Obesity and Sympathetic System (CROSS, 9) study - the following conclusions can be drawn:
- First, antihypertensive drugs acting on the renin-angiotensin system, such as ACE-inhibitors and angiotensin II receptor blockers, have shown clear benefits in risk factors associated with obesity, particularly in insulin sensitivity and glucose metabolism.
- Second, while calcium channel blockers do not appear to be contraindicated, both diuretic and beta-blocking agents have shown to worsen the already impaired metabolic profile and to have diabetogenic effects (10). In the case of beta-blockers, evidence has also been provided that this therapeutic regimen may favour a further body weight increase, presumably via an anti-lipase mediated mechanism (11).
Finally, two further issues should be briefly mentioned. First, central sympatholitic agents may exert favourable metabolic effects by improving insulin sensitivity and ameliorating lipid profile (12). Second, although confined to patients affected with metabolic syndrome, the suggestion has recently been made that goal blood pressure values during antihypertensive treatment should be well below 140/90 mmHg (possibly below 130/80 mmHg in patients with diabetes) (13).
This means that combination therapy is in most instances mandatory to reduce blood pressure values at goal and thus to achieve full cardiovascular protection.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.