Increased glucocorticoid activity in men with cardiovascular risk factors.

The association between hypertension and insulin resistance might be explained by increased activity of the principal glucocorticoid, cortisol. Recent data show that the intensity of dermal vasoconstriction after topical application of glucocorticoids is increased in patients with essential hypertension. In this report, we examine whether increased glucocorticoid sensitivity or secretion is associated with insulin resistance and is a cause or consequence of hypertension. We studied 32 men (aged 47 to 56 years) from a cross-sectional study and 105 men (aged 23 to 33 years) in whom predisposition to high blood pressure has been defined by their own blood pressure and the blood pressures of their parents. In both populations, increased dermal glucocorticoid sensitivity was associated with relative hypertension, insulin resistance, and hyperglycemia. In young men with higher blood pressure whose parents also had high blood pressure, enhanced glucocorticoid sensitivity was accompanied by enhanced secretion of cortisol, enhanced ligand-binding affinities for dexamethasone in leukocytes, and impaired conversion of cortisol to inactive metabolites (cortisone and 5beta-dihydrocortisol). Increased tissue sensitivity to cortisol, amplified by enhanced secretion of cortisol, is a feature of the familial predisposition to high blood pressure rather than a secondary effect of high blood pressure. It may be mediated by an abnormal glucocorticoid receptor, and it may contribute to the association between hypertension and insulin resistance.

Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure.

Increased vascular resistance in essential hypertension occurs mainly in microvessels with luminal diameters < 100 microm. It is not known whether abnormalities in these vessels are a cause or consequence of high blood pressure (BP). We studied 105 men (aged 23-33 yr) in whom predisposition to high blood pressure has been characterized by both their own BP and those of their parents. Factors that are secondary to high BP correlate with offspring BP irrespective of parental BP, but factors that are components of the familial predisposition to high BP are more closely associated with higher BP in offspring whose parents also have high BP. Offspring with high BP whose parents also have high BP had impaired dermal vasodilatation in the forearm following ischemia and heating (289+/-27 [n = 25] versus 529+/-40 [n = 26], 476+/-38 [n = 30], and 539+/-41 flux units [n = 24] in other groups; P < 0.0001) and fewer capillaries on the dorsum of the finger (23+/-0.8 capillaries/0.25 mm2 versus 26+/-0.8 in all other groups; P < 0.003). Except for BP, other hemodynamic indices (including cardiac output and forearm vascular resistance) were not different. The dermal vessels of men who express a familial predisposition to high BP exhibit increased minimum resistance and capillary rarefaction. Defective angiogenesis may be an etiological component in the inheritance of high BP.

Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure.

AIM: To assess the feasibility and utility of a new method to identify factors associated with increased predisposition to high blood pressure in young people. SUBJECTS: Eight hundred and sixty-four people aged 16-24 years and their parents. SETTING: Ladywell Medical Centre, Edinburgh, Scotland, UK. METHOD: Blood pressure was measured in 864 young adults and in both of their parents. Four groups of approximately 50 offspring were selected from the corners of a scatter diagram, with offspring blood pressure scores on one axis and combined parental blood pressure scores on the other. Blood and urine samples were taken for biochemical and genetic analyses. RESULTS: Two groups of offspring had parents with high blood pressure and two groups had parents with low blood pressure. When parental blood pressure was low, comparison of offspring with high and low blood pressure revealed significantly higher mean body mass index in offspring with high blood pressure, but no significant elevation of biochemical or hormonal variables. When parental blood pressure was high, comparison of offspring with high and low blood pressure also revealed a significant difference in body mass index, but in addition, offspring with high blood pressure and high parental blood pressure had higher levels of angiotensinogen, cortisol and 18-OH corticosterone. Restriction fragment length polymorphism analysis revealed that 27% of offspring at the greatest genetic risk (high personal and parental blood pressure) were homozygous for the larger allele of the glucocorticoid receptor gene compared with only 9% of those at lowest genetic risk (low personal and parental blood pressure). CONCLUSION: The combined biochemical and genetic findings suggest that abnormalities of glucocorticoid metabolism and the renin-angiotensin system may help to explain genetic predisposition to high blood pressure. The new sampling method is practicable and could be applied to the investigation of other continuously distributed variables which show familial aggregation.

Prediction of high blood pressure in young people: the limited usefulness of parental blood pressure data.

Blood pressure was measured in 864 young people aged 16-24 years, 8 years after both of their parents had their blood pressures measured as part of the screening phase of the Medical Research Council Mild Hypertension Trial. Only 29% of offspring with a conventional 'family history of hypertension', defined in terms of having at least one parent with a score in the top 10% of the distribution, had a blood pressure score in the top 20% after 8 years. The positive predictive value was increased to 38% in offspring with two parents in the top 20%, but only 4% of offspring met this definition and only 7% of offspring in the top 20% after 8 years were identified by this method. Sensitivity was increased to 46% in offspring with at least one parent in the top 20%, but 33% of offspring met this definition and 74% of them did not have a blood pressure level in the top 20% after 8 years. It is concluded that parental blood pressure data are of limited value for the prediction of high blood pressure in young people and provide no scientific basis for a high risk strategy of prevention.

Health related behaviour in hypertension.

Three groups of patients matched for age and sex were drawn from general practitioner records. One group had been diagnosed as mild hypertensives and were not on any medication, the second group consisted of moderate to severe hypertensives on medication and the third was a quasi-control group consisting of normotensives with no diagnosed medical problem. These three groups were compared with respect to individual behaviours which may affect blood pressure levels. Patients in both hypertensive groups were less likely to be current smokers. They were also more likely to be controlling their weight than people in the control group: well over 50% of men and women in both hypertensive groups as compared with about one-third in the control group. There were no differences between the three groups with respect to reported frequency or amount of alcohol use, frequency of exercise or strategies for coping with stress, although men in the control group were significantly less likely to describe themselves as not very active. We suggest that more advice is needed for hypertensive patients concerning the adverse effects of alcohol, the benefits of exercise and successful methods of weight control. However, the greater propensity of normotensives to smoke may put them more at risk of cardiovascular disease than the hypertensive individuals.