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Query: UMLS:C0028754 (obesity)
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Hyperinsulinemia and insulin resistance have been postulated to link obesity and hypertension. Evidence supporting this concept derives mainly from epidemiological studies showing a correlation between insulin resistance, hyperinsulinemia, and blood pressure and from short-term studies suggesting that insulin has renal and cardiovascular actions that, if sustained, could elevate blood pressure. However, a cause-and-effect relation between insulin and hypertension has not been clearly established. Recent studies indicate that chronic hyperinsulinemia, similar to that found in obese hypertensive patients, did not raise blood pressure in normal dogs, even when renal excretory capability was reduced by prior removal of kidney mass. Chronic insulin infusion also failed to elevate blood pressure in dogs maintained on a high sodium intake and did not potentiate the long-term blood pressure responses to angiotensin II or norepinephrine. The presence or absence of insulin resistance may not be a major factor in determining the blood pressure response to hyperinsulinemia since chronic insulin infusion also failed to cause hypertension in obese, insulin-resistant dogs. Although hyperinsulinemia causes transient sodium retention, sustained decreases in renal excretory capability sufficient to cause chronic hypertension did not occur in dogs. In rats, insulin infusion causes small increases in blood pressure, although several characteristics of the hypertension (e.g., salt-sensitivity) differ from those observed in obese human hypertensive patients. Whether humans more closely resemble dogs or rats with respect to their long-term cardiovascular responses to insulin remains to be determined. However, very high insulin levels in humans with insulinoma do not cause hypertension, and several studies suggest that there is only a weak correlation between plasma insulin concentration and blood pressure in normal humans. Therefore, additional factors besides hyperinsulinemia per se may be responsible for a major component of obesity-associated hypertension.
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PMID:Obesity-associated hypertension. Hyperinsulinemia and renal mechanisms. 173 Apr 54

Methylprednisolone pharmacokinetics and its directly suppressive effects on plasma cortisol, blood histamine (basophils), and circulating helper T cells were evaluated in six obese (at least 35% above ideal body weight) men and six nonobese male volunteers. Methylprednisolone doses of 0.6 mg/kg total body weight were administered as the 21-succinate sodium salt. Absolute clearance (in liters per hour) of methylprednisolone was 40% less in the obese subjects. Total volume of distribution (Vss) of methylprednisolone was unchanged (about 120 L), but when normalized for total body weight, Vss per kilogram was less in obesity. The patterns of cortisol, blood histamine, and helper T cell responses after methylprednisolone administration were similar in both groups, but more profound effects were observed in the obese subjects. Pharmacodynamic models were applied for these immediate effects of methylprednisolone based on the premise that receptor interactions of steroids are followed by rapid suppression of the circadian rhythm of cortisol and recirculation of basophils and helper T cells, which persist until inhibitory concentrations (IC50) of methylprednisolone disappear. Similar IC50 values for the three effects were obtained in both groups, indicating no intrinsic pharmacodynamic differences in sensitivity to these methylprednisolone effects in obesity. However, methylprednisolone should be administered on the basis of ideal body weight, and the dosing interval should be potentially lengthened because of decreased methylprednisolone clearance in obesity.
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PMID:Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity. 182 21

Hypertension and hypertension-related cardiovascular renal sequelae remain major clinical and public health problems in the United States, particularly among African Americans. Compared with whites, African Americans have higher incidence and prevalence rates for hypertension; these differentials are more pronounced in young adult women. Among the very old, race differentials in hypertension prevalence rates are less pronounced. The reasons for the epidemic hypertension rates in the United States are largely environmental: obesity, physical inactivity, high salt and alcohol intake, and psychosocial stress have all been identified as causes. Obesity and physical inactivity probably account for a significant proportion of the premature excess hypertension in African Americans relative to white women. Putative genetic differences between African Americans and whites are unlikely to account for the differential in hypertension rates. During the last 20 years tremendous strides have been made in the identification, treatment, and control of hypertension in the African-American community. Yet, there is further progress to be made. Preventing hypertension precursor conditions (ie, obesity, excess salt intake, psychosocial stressors), normalizing blood pressure levels (less than 140/90 mm Hg), reducing the prevalence of severe hypertension (greater than 160/90 mm Hg), and linking psychosocial correlates of blood pressure to cardiovascular-renal physiology (ie, salt sensitivity) remain as major challenges for those involved in hypertension management and research in African-American communities.
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PMID:Epidemiology of hypertension and hypertensive target-organ damage in the United States. 183 24

Data suggest a critical role for Ca metabolism in the pathophysiology of hypertensive disease. Intracellularly, all hypertension displays elevated cytosolic free-Ca2+ and suppressed free-Mg2+ levels. Extracellularly, however, heterogeneous defects in Ca and Mg metabolism are observed. This apparent divergence may be explained by considering all hypertension as the expression, in varying degrees, of two underlying Ca-related mechanisms: one (salt sensitive, low renin, Ca(2+)-antagonist sensitive) dependent on inappropriate cellular Ca2+ uptake from the extracellular space and the other (salt insensitive, renin dependent, Ca(2+)-antagonist insensitive) dependent on increased cellular Ca2+ release from intracellular sites. Recent work highlights the role of 1,25-dihydroxyvitamin D3 and the newly described parathyroid hypertensive factor in volume-dependent low-renin forms of hypertension. Altered cellular ion handling may also explain metabolic and clinical correlates of hypertension, e.g., peripheral insulin resistance, hyperinsulinemia, obesity, and non-insulin-dependent diabetes mellitus (NIDDM). Thus, all subjects with NIDDM, whether hypertensive or not, display the same elevated cytosolic free-Ca2+ and suppressed free-Mg2+ levels observed in hypertension. Furthermore, adiposity, the level of blood pressure, and fasting and postglucose hyperinsulinemia are all closely and quantitatively related to intracellular free-Ca2+, free-Mg2+, and pH levels. This suggests a broader hypothesis, in which hypertension, obesity, insulin resistance, and NIDDM, each usually considered a distinct clinical entity, represent different clinical expressions of a common defect in cellular ion handling, hence explaining their frequent clinical coexistence in the general population.
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PMID:Calcium metabolism in hypertension and allied metabolic disorders. 186 22

Hypertension has been related to both obesity and a high salt intake. Evidence for the associations of blood pressure with body weight and dietary salt intake is summarized. In both adolescents and adults correlations between blood pressure and weight are highly significant, and in longitudinal studies change in blood pressure over time is correlated with change in weight. Correlations between salt intake and blood pressure are less striking, and the results of trials of modest salt restriction demonstrate a small but significant effect on blood pressure. Individuals vary in their susceptibility to salt, and hypertensive individuals are more responsive than normotensive individuals. Dietary deficiencies of potassium and calcium may amplify the effect of a high salt intake on blood pressure. Animal models provide compelling evidence for a genetic component to salt sensitivity of blood pressure. In two hypertension prevention trials, change in blood pressure was more convincingly related to change in weight than to change in dietary salt. Avoidance of obesity, or weight reduction in overweight individuals, should be key strategies for hypertension prevention. Avoidance of salt excess is also appropriate, although currently available trial data do not justify a recommendation of rigorous salt restriction for the entire population.
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PMID:Nutrition and hypertension prevention. 188 52

An overview of published observations suggests that both genetic predisposition and environment work together to produce hypertension in most persons. High blood pressure before age 55 occurs 3.8 times more often among persons with a strong positive family history of high blood pressure. Much of the total variability in blood pressure in modern populations seems attributable to genetic factors. Estimates of the proportion of the variance attributable to all genetic factors (heritability [H2]) vary from 25% in pedigree studies to 65% in twin studies for sitting diastolic blood pressure. Several biochemical traits associated with high blood pressure are highly genetic (H2, 78-84%) and may help elucidate the pathophysiology of high blood pressure. While pertinent environmental factors such as salt intake, alcohol use, and amount of exercise also correlate significantly among relatives, only 7% of the total variance of diastolic blood pressure seems attributable to all shared environmental factors in family households. Thus most familial aggregation of high blood pressure appears to be due to genes rather than shared family environment. Practical benefit may result from identifying familial predisposition in multiple siblings with high blood pressure before age 55 and lipid abnormalities (labeled "familial dyslipidemic hypertension"). About 12% of high blood pressure patients have familial dyslipidemic hypertension and also have high risk of early coronary heart disease. Hyperinsulinemia and central obesity as well as high triglycerides and low high density lipoprotein cholesterol are prominent features of familial dyslipidemic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Are there interactions and relations between genetic and environmental factors predisposing to high blood pressure? 188 56

Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults.
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PMID:Childhood predictors of future blood pressure. 188 60

This report deals with three aspects of risk related to blood pressure and high blood pressure. The first aspect of risk concerns distributions of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the adult population and their relation to long-term risk of morbidity and mortality. By middle age, only a minority (about 20%) of Americans have optimal SBP and DBP levels, less than 120 mm Hg and less than 80 mm Hg, respectively. For the majority with higher levels, risks of major clinical events, including death from cardiovascular diseases and from all causes, are markedly increased. The relations of SBP and DBP with risk are strong, continuous, and graded. Risk is sizable not only for persons with high blood pressure by usual clinical criteria (SBP greater than or equal to 140 mm Hg or DBP greater than or equal to 90 mm Hg), but also for those with "high-normal" blood pressure (e.g., SBP 130-139 mm Hg or DBP 80-89 mm Hg). Thus, the blood pressure problem is a population-wide one and requires for its control a combined population-wide and high-risk strategy. A major component of this strategy must be nutritional-hygienic measures for the primary prevention of the rise in blood pressure during adulthood and of high blood pressure (i.e., primary prevention not only of the complications of high blood pressure but also of high blood pressure itself) through improved lifestyles having the potential to shift downward the blood pressure distribution of the whole population. The second aspect of risk concerns the known risk factors (i.e., aspects of modern lifestyle) leading to the mass occurrence of blood pressure rise during adulthood and of high blood pressure. These risk factors are high salt intake, high dietary sodium/potassium ratio, calorie imbalance and resultant obesity, and high alcohol intake. The extensive data base establishing the role of these common traits in the etiology of the blood pressure/high blood pressure problem is the scientific foundation for efforts to achieve the primary prevention of high blood pressure. The third aspect of risk relates to the combined impact of other risk factors along with blood pressure-high blood pressure in markedly increasing the probabilities of morbidity and mortality (e.g., "rich" diet, diet-dependent serum cholesterol and uric acid, smoking, diabetes, and target-organ damage). Prevention and control of lifestyle-related traits are essential components of the strategy for dealing with the blood pressure-high blood pressure problem.
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PMID:Blood pressure and high blood pressure. Aspects of risk. 188 62

Epidemiologic research indicates that glucose intolerance and hypertension are interrelated phenomena, each powerfully predisposing to atherosclerotic cardiovascular disease. Both diabetic and hypertensive patients have greater amounts of atherogenic risk factors, including dyslipidemia, hyperuricemia, elevated fibrinogen, and left ventricular hypertrophy. Diabetic persons have an increased prevalence of hypertension (50%), and glucose intolerance is more common in hypertension (15% to 18%). Both share a strong relationship to excess weight, but the excess of hypertension in diabetic persons occurs in both lean and obese subjects. Diabetes doubles the risk of hypertension associated with overweight. The risk of coronary disease, stroke, and peripheral arterial disease increases with increasing blood pressure to the same degree in diabetic persons as in nondiabetic persons, but at any level of blood pressure, diabetic persons have a doubled risk of these outcomes. Both diabetic and hypertensive patients are particularly prone to silent or unrecognized myocardial infarctions. Greater efforts at primary prevention of both hypertension and diabetes are clearly needed, including efforts at weight control, exercise, limitation of salt intake, and control of blood lipid levels. In either diabetic or hypertensive candidates for cardiovascular disease, optimization of the chances of avoiding sequelae requires a comprehensive multifactorial approach. Prevention requires more than normalization of either the blood sugar or blood pressure. Rational preventive measures must also include weight reduction, a fat-modified diet, cessation of smoking cigarettes, raising high-density lipoprotein, lowering low-density lipoprotein, and reduction of fibrinogen. Hypertension, obesity, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol tend to coexist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The epidemiology of impaired glucose tolerance and hypertension. 200 55

Isolated systolic hypertension (ISH) is a common disorder in the elderly, carrying with it a high risk of cardiovascular morbidity and mortality. Environmental and age-related factors believed to contribute to ISH include obesity, declining physical activity, stress, and such dietary changes as increased salt intake and decreased intake of calcium and potassium. Increased rigidity of the aorta resulting in reduced compliance is an important hemodynamic feature, but factors that increase peripheral resistance also appear to play a role. Antihypertensive drugs have been shown to effectively and safely lower the systolic blood pressure elevations characteristic of ISH. To date, use of low drug doses and careful titration of dosage have avoided significant orthostatic hypotension and undue lowering of the diastolic pressure. Studies of relatively small groups of patients suggest that antihypertensive drugs can lower the risk of cardiovascular morbidity/mortality associated with ISH but the definitive answer awaits results of the ongoing large-scale Systolic Hypertension in the Elderly Program trial. In the interim, management should begin with conservative measures such as weight loss, salt restriction and, possibly, calcium supplementation. If this fails, drug therapy should be considered in patients with systolic blood pressures above 180 mm Hg and in those with systolic readings between 160 and 180 mm Hg who have concomitant cardiovascular risk factors. To date, no controlled trials of sufficient size have demonstrated that one drug class is more effective than another in treating ISH. Drug therapy should be tailored to the individual patient, starting with a low dose of a single drug and, if necessary, slowly increasing dosage until a systolic blood pressure under 160 mm Hg is attained.
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PMID:Epidemiology, pathophysiology, and management of isolated systolic hypertension in the elderly. 201 51


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