Association of Obesity And Hypertension
Obesity has been called the epidemic of our time with approximately 70% of the adults in the United States either overweight or obese according to the American Heart Association (AHA) and the American Physiological Society. Estimates based on risk suggest that as much as 65% to 70% of essential hypertension occurs in association with obesity, although longitudinal population based studies indicate a somewhat lower figure. It is nonetheless abundantly clear that obesity is closely associated with hypertension, with a 6.5 mm Hg increase in systolic blood pressure (SBP) for each 10% increase in body weight. The importance of this association is the cardiovascular (CV) risk related to both obesity and hypertension.
Assessment of Overweight and Obesity
Calculation of body mass index (BMI) is commonly used as the basic measure of obesity. Calculated from the weight in kilograms divided by height in meters squared, the BMI gives a convenient if imperfect measure of obesity. BMI should be recorded as part of every physical examination. A BMI below 25 is considered normal, whereas overweight is indicated by a BMI of 25 to 30, and obesity by a BMI of over 30. Body fat distribution also plays a critical role in the CV risk imposed by obesity.
Body Fat Distribution
Because the upper body or abdominal form of obesity is the phenotype associated with enhanced CV risk, as compared with the lower body or gluteal form, assessment of this variable should be made for each obese or overweight individual. A convenient surrogate measurement for body fat distribution is the abdominal circumference. Over 40 inches (102 centimeters) in men and over 35 inches (88 centimeters) in women signifies the upper body form of obesity. Waist to hip ratio (W/H) has also been used to identify the upper body abdominal form of obesity but is more cumbersome and bedeviled by locating the proper places on the torso to make the measurements. W/H of over 1 in men and over 0.85 in women are indicative of the upper body phenotype. It has recently been demonstrated that even patients with a normal BMI have increased cardiovascular risk when the abdominal circumference is increased. In patients with obese arms, a large BP cuff should be used to avoid the artifact resulting from the use of too small a cuff.
Pathophysiology of Obesity-Related Hypertension
Understanding the mechanisms associated with obesity-related hypertension provides the rationale for appropriate therapy.
Historical Milestones
Although the association of obesity with hypertension had been recognized since the measurement of blood pressures in populations in the early 1900s, the underlying mechanisms linking blood pressure (BP) and body weight were not understood until the late 1980s. The linkage of BP and obesity was reinforced by the Framingham Heart Study in the 1960s with the prospective demonstration that body weight and weight gain predicted the development of hypertension. It also became clear, by comparing obese normotensive with obese hypertensive subjects, that trivial attributions such as cuff artifact, increased salt intake, increased plasma volume, and hemodynamic factors related to cardiac output could not explain the increased peripheral resistance noted in obese hypertensives.
The pathophysiology was eventually clarified by a number of observations and studies as follows:
- 1.
The impact of body fat distribution: The French clinician Jean Vague noted in the 1940s and 1950s that obesity phenotype influenced the CV and metabolic complications of obesity. These complications tracked with the upper body abdominal form of obesity, which he called “android,” rather than the lower body gluteal femoral form, which he referred to as “gynoid.” Little noted until the 1980s, Vague’s observations were strongly reinforced by large scale epidemiologic studies from Scandinavia that convincingly demonstrated that waist to hip ratio, a surrogate for the upper body phenotype, predicted CV risk (myocardial infarction, hypertension), type 2 diabetes, and overall mortality.
- 2.
The role of insulin: At the same time both epidemiological and clinical studies demonstrated that insulin resistance, hyperinsulinemia, and type 2 diabetes also tracked with the upper body phenotype. Insulin thus emerged as a valid risk factor for CV in general and hypertension in particular. Insulin influences BP by stimulating the sympathetic nervous system (SNS) as shown in Fig. 35.1 and by enhancing renal sodium reabsorption.
FIG. 35.1
Insulin stimulates the sympathetic nervous system (SNS). A, Plasma NE levels rise during euglycemic hyperinsulinemic clamp shown here in nine lean normotensive young men. Cardiovascular indices of SNS stimulation (pulse rate, pulse pressure, cross product, and mean arterial pressure) increased during the clamp. (Modified from Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta JA, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man . Diabetes. 1981;30:219-225.) B, Muscle sympathetic nerve activity (MSNA) increases during euglycemic hyperinsulinemic clamp. Insulin levels were within the physiologic range.
(From Hausberg M, Mark AL, Hoffman RP, Sinkey CA, Anderson EA. Dissociation of sympathoexcitatory and vasodilator actions of modestly elevated plasma insulin levels. J Hypertens. 1995;13:1015-1021.)
- 3.
Role of the SNS: Contrary to widely held beliefs at the time, SNS activity was shown to be increased in the obese in the early 1990s ( Fig. 35.2 ). SNS stimulation increases cardiac output, peripheral resistance, and, importantly, renal sodium reabsorption.
FIG. 35.2
Sympathetic activity increases with increased body weight. A, 24-hour urinary NE excretion increases as a function of body mass index and waist to hip ratio.
(Modified from Troisi RJ, Weiss ST, Parker DR, Sparrow D, Young JB, Landsberg L. Relation of obesity and diet to sympathetic nervous system activity. Hypertension. 1991;17:669-677.) B, Muscle sympathetic nerve activity (MSNA) increases as a function of body weight. (From Scherrer U, Randin D, Tappy L, Vollenweider P, Jéquier E, Nicod P. Body fat and sympathetic nerve activity in healthy subjects. Circulation. 1994;89:2634-2640.)
- 4.
Role of leptin: Leptin, the polypeptide product of the ob/ob gene, is synthesized in white adipose tissue; levels are higher in the obese, reflective of the fat mass of the individual. Acting at the level of the central nervous system, leptin suppresses appetite and stimulates the SNS ( Fig. 35.3 ).
FIG. 35.3
Leptin infusion increases sympathetic nervous system activity in rats.
(From Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI. Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest. 1997;100:270-278.)
- 5.
Role of the renin-angiotensin-aldosterone system (RAAS): In addition to stimulation of renin release by the SNS, it has become clear that adipose tissue synthesizes all the components of the RAAS including aldosterone. Obesity related hypertension is associated with increased levels of angiotensin II and aldosterone. High circulating levels of free fatty acids in obesity may also contribute to the increased secretion of aldosterone, by mechanisms that remain obscure.
- 6.
Obstructive sleep apnea (OSA): OSA, more common in the obese as compared with lean individuals, is recognized as a cause of both hypertension and SNS stimulation. In the obese fatty infiltration of the genioglossus muscle, which pulls the base of the tongue forward in the first phase of respiration, is the likely cause.
The Pressure-Natriuresis Relationship and Salt Sensitivity
As would be anticipated from the activation of the SNS and the RAAS, the hypertension of obesity is salt sensitive. The pressure-natriuresis relationship is shifted to the right by NE, insulin, and A II, all of which increase renal avidity for sodium ( Fig. 35.4 ). The increase in BP overcomes the natriuretic handicap so volume is not expanded; the increase in BP is compensation for the increase in renal avidity for salt.
Sympathetic Stimulation and the Metabolic Economy of the Obese State
Can the linkage of obesity and hypertension, a linkage in which SNS stimulation plays a major role, be part of a metabolic adaptation to the obese state? Because SNS stimulation increases energy expenditure it has been proposed that SNS activation is a mechanism recruited in the obese to restore energy balance and limit further weight gain. This hypothesis ( Fig. 35.5 ) has substantial experimental support.
The Metabolic Syndrome and Cardiovascular Risk
Since the early 1990s it has been recognized that obesity related hypertension is frequently associated with other cardiovascular risk factors ( Table 35.1 ).
| Four cardinal features |
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| Frequently associated |
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Critical Components of the Metabolic Syndrome
The four crucial components are abdominal obesity, insulin resistance (and consequent hyperinsulinemia), hypertension, and a characteristic dyslipidemia (low high-density lipoprotein [HDL]-cholesterol and high triglycerides). Considerable debate exists as to whether this constitutes a distinct syndrome, although it seems clear that these abnormalities occur together more frequently than could be accounted for by chance alone. In addition, different diagnostic criteria have been proposed by various national and international panels ; the differences in criteria are, in general, small and overlapping, reflective of differences in emphasis on the four cardinal manifestations noted above. From a practical standpoint the importance of the metabolic syndrome is the recognition that these abnormalities occur together and that they convey significant CV risk. Estimates from the third National Health and Nutrition Examination Survey suggest that about 30% of adults in the U.S. have metabolic syndrome; because the incidence increases with age the figure for people over 60 years old is closer to 40%.
In addition to the four critical components, other abnormalities have been noted to occur frequently in patients with metabolic syndrome, including: impaired glucose tolerance and type 2 diabetes; microalbuminuria and impaired renal function; increased plasminogen activator inhibitor (PAI-1); hyperuricemia; small dense LDL-cholesterol; and markers of inflammation.
The thread that ties the various manifestations together is insulin resistance and the resultant hyperinsulinemia.
Insulin and the Metabolic Syndrome
Insulin, the major anabolic hormone of the fed state, has a myriad of biological actions but most prominent is the stimulation of glucose uptake in skeletal muscle. Insulin resistance, defined operationally, is an impairment in insulin-mediated glucose uptake in muscle. As a consequence of this impairment, blood glucose levels rise stimulating the release of insulin from the pancreatic beta cells. The increase in insulin compensates, partially, for the insulin resistance but results in hyperinsulinemia. When beta cell capacity to compensate for insulin resistance is exhausted impaired glucose tolerance and type 2 diabetes ensue. Patients with metabolic syndrome have increased SNS activity, as shown in Fig. 35.6 . The increased levels of insulin, along with leptin, stimulate the SNS contributing to the hypertension ( Fig. 35.6 ). The increased levels of insulin are also the proximate cause of the dyslipidemia by stimulating hepatic very low-density lipoprotein synthesis.
Cardiovascular Risk of Obesity-Related Hypertension
The cardiovascular risk associated with hypertension (myocardial infarction, stroke, heart failure, and renal failure) is well recognized. Although much of the CV risk associated with obesity is secondary to the comorbidity of hypertension and type 2 diabetes, evidence suggests that the long-term risk of CV disease is accentuated by obesity in additive fashion with that of hypertension ( Fig. 35.7 ). If carbohydrate intolerance develops, the risk of course is greatly accelerated.
Treatment of Obesity-Related Hypertension
Management of Obesity-Related Hypertension by Lifestyle Changes
Management of obesity is crucial in the treatment of obesity-related hypertension. Decreasing fat burden decreases blood pressure, increases responsiveness to antihypertensive medications, and beneficially affects other cardiac risk factors while preventing or delaying the development of type 2 diabetes. Weight loss and the development of a healthy lifestyle is the cornerstone in the treatment of the obese hypertensive patient. It is applicable in every case. The clinician must form a partnership with the patient, to motivate, educate, and instruct; this partnership should result in the development of a plan that takes into account the patients’ health status, goals, and unique problems. Successful weight loss that is sustained will almost always require a team of professionals, including dieticians, nurses, nurse practitioners, physician assistants, and access to psychologists and exercise physiologists. An individual’s weight loss plan is often best addressed by enrollment in a bona fide weight loss program headed by a physician trained in obesity management. These programs frequently stress behavioral modification techniques that have had documented success at achieving long-term weight loss. A reasonable initial goal for weight loss is about 10% of total body weight.
The major components of lifestyle management are: low energy diets; salt restriction; increased potassium and magnesium intake; increased physical activity; and alcohol moderation ( Table 35.2 ).
| Low energy diets |
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| Sodium restriction |
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| Physical activity |
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| Alcohol moderation |
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