Maximizing the benefit of treatment in mild hypertension:three simple steps to improve diagnostic accuracy.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Most patients only have three measurements of blood pressure before being labelled as hypertensive. This may lead to inaccurate classification, unnecessary treatment and dilution in treatment benefit for the population. Aim: To examine the accuracy of current methods of diagnosing mild hypertension, and to explore ways to improving targeting of antihypertensive treatment without entailing lengthy observation. DESIGN: Re-analysis of published data. METHODS: We tested current diagnostic methods using the data for 3965 individuals who were followed for a year in the placebo arm of the MRC Mild Hypertension Trial. We calculated the proportion selected for treatment by current methods and the diagnostic accuracy, using average blood pressure beyond 6 months as representing 'true' long-term blood pressure. We examined the benefit of averaging blood pressures, of prolonging observation modestly and of estimating within-person blood pressure variability. RESULTS: Prolonging observation to 3 months selects a smaller (by about 12%) proportion of the sample for treatment, a proportion similar to that defined as 'truly' hypertensive. The diagnostic accuracy of current methods is poor, with up to 69% discrepancy in classification. This discrepancy was improved by up to 18% in absolute terms by prolonging observation to 3 months and using average blood pressures. Identifying those individuals with low within-person variability allows marked improvement in the prediction of 'true' hypertension. DISCUSSION: Although some inaccuracy in the diagnosis of hypertension is inevitable, observation for 3 months, averaging blood pressures and estimating within-person blood pressure variability can markedly improve upon current practice

Association between size at birth, truncal fat and obesity in adult life and its contribution to blood pressure and coronary heart disease; study in a high birth weight population.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: The aim of the study was to assess the relationship between size at birth and obesity as well as truncal fat, and its contribution to cardiovascular risk in a high birth weight population. DESIGN: Cohort-study with retrospectively collected data on size at birth. SETTING: Reykjavik, Iceland. SUBJECTS: A total of 1874 men and 1833 women born in Reykjavik during 1914-1935. MAIN OUTCOME MEASURES: Size at birth. Adult weight, height and skinfold thickness measurements, systolic and diastolic blood pressure, fatal and nonfatal coronary heart disease (CHD). RESULTS: Birth weight was positively related to adult body mass index (BMI) in both genders (B=0.35+/-0.14 kg/m(2), adj. R(2)=0.015, P=0.012 and B=0.34+/-0.17 kg/m(2), adj. R(2)=0.055, P=0.043 in men and women, respectively). However, high birth weight was not a risk factor for adult obesity (BMI>/=30 kg/m(2)). In the highest birth weight quartile, the odds ratio (95% CI) for being above the 90th percentile of truncal fat was 0.7 (0.6-1.0, P=0.021) for men and 0.4 (0.3-0.8, P=0.002) for women, compared with the lowest birth weight quartile. Truncal fat and BMI were positively related to blood pressure in both genders (P<0.05), but not to CHD. The regression coefficient for the inverse association between birth weight and blood pressure hardly changed when adding truncal fat to the model. CONCLUSION: In this high birth weight population, high birth weight was related to higher BMI in adulthood without being a risk factor for adult obesity. The inverse association between birth weight and truncal fat in adulthood suggests a role for foetal development in determining adult fat distribution. The inverse relationship of birth weight to blood pressure seems not to be mediated through the same pathway as to truncal fat

Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2

Deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in humans leads to the syndrome of apparent mineralocorticoid excess (SAME), in which cortisol illicitly occupies mineralocorticoid receptors, causing sodium retention, hypokalemia, and hypertension. However, the disorder is usually incompletely corrected by suppression of cortisol, suggesting additional and irreversible changes, perhaps in the kidney. To examine this further, we produced mice with targeted disruption of the 11β-HSD2 gene. Homozygous mutant mice (11β-HSD2(–/–)) appear normal at birth, but ∼50% show motor weakness and die within 48 hours. Both male and female survivors are fertile but exhibit hypokalemia, hypotonic polyuria, and apparent mineralocorticoid activity of corticosterone. Young adult 11β-HSD2(–/–) mice are markedly hypertensive, with a mean arterial blood pressure of 146 ± 2 mmHg, compared with 121 ± 2 mmHg in wild-type controls and 114 ± 4 mmHg in heterozygotes. The epithelium of the distal tubule of the nephron shows striking hypertrophy and hyperplasia. These histological changes do not readily reverse with mineralocorticoid receptor antagonism in adulthood. Thus, 11β-HSD2(–/–) mice demonstrate the major features of SAME, providing a unique rodent model to study the molecular mechanisms of kidney resetting leading to hypertension. J. Clin. Invest. 103:683–689 (1999

Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility--Reykjavik Study (AGES-R).

To access full text version of this article. Please click on the hyperlink "View/open" at the bottom of this pageWe aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus. The study population consisted of 4,994 persons aged ≥ 67 years, who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA(1c) ≥ 6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses. The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA(1c), insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria. Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged.NIH N01-AG-12100 NIH/NIA, National Eye Institute (NEI) of the NIH ZIAEY000401, Hjartavernd (the Icelandic Heart Association), Althingi (the Icelandic Parliament), University of Iceland

The case for home monitoring in hypertension

Although the assessment of cardiovascular risk in individual patients takes into account a range of risk factors, the diagnosis and management of hypertension (high blood pressure) is largely determined by a single numerical value, albeit that often several readings are taken over time. Given the critical impact of a decision to embark on lifelong drug therapy, the importance of ensuring that a blood pressure (BP) record is both accurate and representative is clear. However, there is good evidence that the variability of BP is such that even if measurement is of the highest quality, it can be difficult to say with confidence whether a patient is above or below a treatment threshold. This commentary argues that current BP measurement is inadequate to make the clinical decisions that are necessary and that multiple readings are required to deliver an acceptable degree of accuracy for safe decision-making. This is impractical in a doctor's surgery, and the only realistic long-term strategy is to involve the patient in measuring his or her own BP in their own environment. Evidence is presented that such a strategy is better able to predict risk, is cost-effective for diagnosing hypertension, can improve BP control and is thus better able to protect individuals in the future