We conclude that catestatin is diminished early in the course of development of hypertension, even in the normotensive offspring of patients with the disease. Low catestatin predicts augmented adrenergic pressor responses, suggesting a mechanism whereby diminished catestatin might increase the risk for later development of hypertension.

Abstract-Oxygen free radicals, including hydrogen peroxide, may mediate oxidative stress in target organ tissues and contribute to cardiovascular complications in hypertension. To examine heritability of hydrogen peroxide production, we investigated this trait in a family-based cohort consisting of family members (nϭ236) ascertained through probands (nϭ57) with essential hypertension. Significant effects on hydrogen peroxide production were found for gender and ethnicity, with men having greater values than women (PϽ0.001) and white subjects having greater values than black subjects (Pϭ0.025). Hydrogen peroxide production correlated directly with plasma renin activity (Pϭ0.015), suggesting an important interaction between circulating oxygen radicals and the renin-angiotensin system and a potential mechanism for lower hydrogen peroxide values observed in blacks. Heritability estimates from familial correlations revealed that approximately 20% to 35% of the observed variance in hydrogen peroxide production could be attributed to genetic factors, suggesting a substantial heritable component to the overall determination of this trait. Hydrogen peroxide production negatively correlated with cardiac contractility (rϭϪ0.214, Pϭ0.001) and renal function (rϭϪ0.194, Pϭ0.003). In conclusion, these results indicate that hydrogen peroxide production is heritable and is related to target organ function in essential hypertension. Genetic loci influencing hydrogen peroxide production may represent logical candidates to investigate as susceptibility genes for cardiovascular target organ injury. Key Words: genetics Ⅲ hypertension, essential Ⅲ oxygen free radicals T here is increasing evidence that reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxyl radical may play a role in the development of organ damage associated with cardiovascular disease in general and hypertension in particular. We recently found evidence to suggest that hypertensive patients exhibit a significantly higher production of plasma peroxide than normotensive subjects. 1 In addition, among still-normotensive subjects, those with a family history of hypertension have a higher production of plasma peroxide than those normotensives without a family history of hypertension. These findings suggest that there may be a genetic component that leads to elevated production of hydrogen peroxide. A number of recent studies in experimental models with genetic forms of hypertension (spontaneously hypertensive rats, saltdependent Dahl hypertensive rats) have also demonstrated a significantly enhanced level of oxidative stress in the endothelial cells of arteriolar as well as venular segments of the circulation. [2][3][4][5] These studies in genetic models of hypertension also suggest the hypothesis that a phenotype associated with an enhanced level of oxidative stress may ultimately have a heritable component in hypertension.We therefore investigated hydrogen peroxide production in a family-based cohort, ascertained through probands with essential ...

OBJECTIVE -We evaluated the role of a single measurement of HbA 1c in a diabetes case finding in hospitalized patients with random hyperglycemia at admission. RESEARCH DESIGN AND METHODS -From 20March to 31 July 2000, 508 patients admitted through the emergency department of one hospital were tested for random hyperglycemia (plasma glucose [PG] Ͼ125 mg/dl). Consenting patients with hyperglycemia (without preexisting diabetes or on corticosteroids) underwent testing for HbA 1c levels, two fasting PG levels, and an outpatient oral glucose tolerance test (OGTT) if necessary.RESULTS -Of the patients, 50 (9.8%) met the inclusion criteria. Of these, 70% (n ϭ 35) completed the study, and 60% (n ϭ 21) were diagnosed with diabetes. Patients with diabetes had higher HbA 1c levels than subjects without diabetes (6.8 Ϯ 0.4 vs. 5.3 Ϯ 0.1%, P ϭ 0.002). An HbA 1c level Ͼ6.0% was 100% specific (14/14) and 57% sensitive (12/21) for the diagnosis of diabetes. When a lower cutoff value of HbA 1c at 5.2% was used, specificity was 50% (10/21) and sensitivity was 100% (7/14). CONCLUSIONS -In acutely ill patients with random hyperglycemia at hospital admission, an HbA 1c Ͼ6.0% reliably diagnoses diabetes, and an HbA 1c level Ͻ5.2% reliably excludes it (paralleling the operating characteristics of the standard fasting glucose measurements); however, the rapidity of the HbA 1c level can be useful for diabetes case finding and treatment initiation early in the hospital course.

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Multiple heritable traits are associated with essential (genetic) hypertension in humans. Because chromogranin A is increased in both human and rodent genetic hypertension, we examined the influence of heredity and blood pressure on chromogranin A in humans. In estimates derived from among- and within-pair variance in monozygotic versus dizygotic twins, plasma chromogranin A displayed significant (F15,18 = 2.93, P = .016) genetic variance (sigma 2 g), and its broad-sense heritability was high (h2B = 0.983). Plasma chromogranin A was increased in essential hypertension (99.9 +/- 6.7 versus 62.8 +/- 4.7 ng/mL, P < .001) but was influenced little by genetic risk for (family history of) hypertension (in normotensive or hypertensive subjects), by race, or by several antihypertensive therapies (angiotensin-converting enzyme inhibitor, diuretic, or beta-adrenergic antagonist). In normotensive subjects at genetic risk for essential hypertension, neither basal nor sympathoadrenal stress-evoked chromogranin A differed from values found in subjects not at risk. In established essential hypertension, plasma chromogranin A responses to adrenal medullary (insulin-evoked hypoglycemia) or sympathetic neuronal (dynamic exercise) activation were exaggerated, whereas responses to sympathoadrenal suppression (ganglionic blockade) were diminished, suggesting increased vesicular stores of chromogranin A and an adrenergic origin of the augmented chromogranin A expression in this disorder. We conclude that plasma chromogranin A displays substantial heritability and is increased in established essential hypertension. Its elevation in established hypertension is associated with evidence of increased vesicular stores of the protein and with adrenergic hyperactivity but is influenced little by customary antihypertensive therapies. However, the chromogranin A elevation is not evident early in the course of genetic hypertension.