Results of the pilot study for the Hypertension in the Very Elderly Trial

BACKGROUND: The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality. OBJECTIVES: To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues. METHODS: The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months. RESULTS: In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01). CONCLUSIONS: The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.     

Task Force I: methodological aspects of blood pressure measurement

OBJECTIVE: To reach a consensus on important methodological aspects of blood pressure measurement. METHODS: A Task Force on the methodological aspects of blood pressure measurement wrote this review after the Eighth International Consensus Conference on Blood Pressure Monitoring, in Sendai, Japan (28-31 October 2001). This consensus paper is based on the papers presented by Task Force I and on the discussion sessions, and is therefore representative of a broad spectrum of expert opinion. POINTS OF CONSENSUS: Consensus was reached on the following five issues: (1) there is an urgent need for a simplified protocol for the validation of blood pressure measuring devices; (2) there is a need for a means of updating the "state of the market" for validated devices so that users can have easy access to this information; (3) new devices must be validated independently, and existing devices that have not been validated must be reappraised; (4) manufacturers should confirm when new models use algorithms which have been validated previously; (5) the Food and Drug Administration now accepts that when ambulatory blood pressure measurement is used in clinical short-term trials in which side-effects are not being assessed, a placebo arm is not required.     

Cerebral complications of hypertension

Ischaemic and degenerative brain diseases are a major health problem leading to a devastating loss of autonomy. Hypertension has been shown to carry an increased risk not only for cerebrovascular morbidity and mortality but also for cognitive impairment and dementia. Although diastolic blood pressure is considered an important risk factor, it is now clear that isolated systolic hypertension and elevated pulse pressure also play an important role in the development of brain complications. Therefore the treatment of these conditions must urgently become a widespread tool of prevention. All the randomised placebo-controlled trials completed for the last 30 years have shown a reduction in fatal and/or non-fatal strokes. In the most recent trials in isolated systolic hypertension in older patients, the benefit was even greater because of the higher risk in these populations. The new classes of drugs, in particular, calcium-channels blockers and angiotensin-converting enzyme inhibitors, have been shown to be as effective as the originally used diuretics and beta-blockers. Active treatment in the Syst-Eur trial based on nitrendipine as first step, possibly associated with enalapril and/or hydrochlorthiazide reduced not only stroke and cardiovascular complications but also the incidence of dementia including Alzheimer's disease. This important finding must be confirmed by further trials specifically focusing on the prevention of dementia. In addition, the importance of pulse pressure as a risk factor, underlines the need for new drugs which could increase aortic distensibility and decrease systolic blood pressure without greatly reducing diastolic pressure. Improving the management of hypertension offers new opportunities to reduce age-related disease in older people and to promote healthy aging.     

Treatment of diabetic patients with hypertension

This review attempts to highlight the potential of calciumchannel blockers in the prevention of sequelae of diabetes mellitus and hypertension in patients who have both disorders. Evidence-based medicine is driven by the results of randomized, clinical trials. Major contributions were therefore derived from post hoc analyses of the diabetic patients enrolled in placebo-controlled trials, such as Systolic Hypertension in the Elderly Program (SHEP), Systolic Hypertension in Europe (Syst-Eur), and Systolic Hypertension in China (Syst-China), and stepped-care blood-pressure-oriented trials, such as the Hypertension Optimal Treatment (HOT) and United Kingdom Prospective Diabetes Study (UKPDS). Several studies, such as the Fosiniprl; versus Amlodipine Cardiovascular Events Trial (FACET) and Appropriate Blood Pressure Control in Diabetes (ABCD) Trial, have compared the relative merits of angiotensin-converting enzyme and calcium-channel blockers in preserving renal function and metabolic balance in diabetic patients with hypertension, but their publications focused on cardiovascular disorders, which were only secondary end points. On balance, the articles reviewed prove that dihydropyridine calcium-channel blockers score particularly well in the prevention of cardiovascular complications in diabetic patients with hypertension.     

Blood lead concentration, renal function, and blood pressure in London civil servants.

Blood lead concentration was measured in 398 male and 133 female London civil servants not subject to industrial exposure to heavy metals. The relation between blood lead and serum creatinine concentrations and blood pressure were examined. Blood lead concentration ranged from 0.20 to 1.70 mumol/l with a geometric mean concentrations of 0.58 mumol/l in men and 0.46 mumol/l in women (p less than 0.001). In women blood lead concentration increased with age (r = +0.27; p = 0.002). In the two sexes blood lead concentration was positively correlated with the number of cigarettes smoked a day (men r = +0.17 and women r = +0.22; p less than or equal to 0.01), with the reported number of alcoholic beverages consumed a day (men r = +0.34 and women r = 0.23; p less than 0.01), and with serum gamma-glutamyltranspeptidase (men r = +0.23 and women r = +0.14; for men p less than 0.01). Blood lead concentration was not correlated with body weight, body mass index, and employment grade. In men 14% of the variance of blood lead concentration was explained by the significant and independent contributions of smoking and alcohol intake and in women 16% by age, smoking, and alcohol consumption. In men serum creatinine concentration tended to rise by 0.6 mumol/l (95% confidence interval from -0.2 to +1.36 mumol/l) for each 25% increment in blood lead concentration. In men and women the correlations between blood lead concentration and systolic and diastolic blood did not approach statistical significance. In conclusion, in subjects not exposed to heavy metals at work gender, age, smoking, and alcohol intake are determinants of blood lead concentration. At a low level of exposure, lead accumulation may slightly impair renal function, whereas blood pressure does not seem to be importantly influenced. Alternatively, a slight impairment of renal function may give rise to an increase in blood lead concentration.     

Blood pressure and urinary cations in urban Bantu of Zaire

The 24-hour urinary excretion of sodium, potassium, calcium, and magnesium and their relationship to arterial blood pressure were investigated from December 1983 to May 1984 in a 10% random sample (n = 666) of urban Bantu of Kinshasa, Za?re. In youths aged 10-19 years, blood pressure averaged 109/60 mmHg, and the 24-hour urinary excretion of sodium, potassium, calcium, and magnesium averaged 84 mmol, 30 mmol, 483 mumol, and 2 mmol, respectively. After adjustment for age and body weight, a weak positive association became apparent between diastolic pressure and the urinary sodium to potassium ratio in girls and all youths. In adults aged greater than or equal to 20 years, blood pressure averaged 124/72 mmHg, and the 24-hour urinary excretion of sodium, potassium, calcium, and magnesium averaged 87 mmol, 33 mmol, 828 mumol, and 1.88 mmol, respectively. After adjustment for sex, age, body weight, and pulse rate in all adults, systolic pressure was significantly and positively correlated with urinary sodium excretion and negatively correlated with urinary potassium excretion, while diastolic pressure was weakly associated with urinary calcium excretion. In women, an independent and significant association was also observed between systolic pressure and 24-hour urinary sodium. When instead of the 24-hour urinary excretion of sodium and potassium, the sodium to potassium ratio was considered as an independent variable in multiple regression analysis, both systolic and diastolic pressure were independently and positively related to the sodium to potassium ratio in all adults. These results indicate that in this urban Bantu population, age and body weight are the major predictors of systolic pressure in youths and the major predictors of both systolic and diastolic pressure in adults. The sodium to potassium ratio did contribute to the prediction of blood pressure in girls and when, in youths as well as in adults, both sexes were considered together. Urinary calcium was associated with diastolic pressure only in all adults.     

Renal artery stenosis: evaluation with intravenous digital subtraction angiography

The ability of diagnostic intravenous digital subtraction angiography (IVDSA) to demonstrate the degree of renal artery stenosis was compared with that of intraarterial angiography in 45 patients with 92 arteries. Stenotic lesions on both IVDSA and intraarterial studies were classified as normal (0% stenosis), minor (less than 50%), low grade (50%-80%), and high grade (80%-99%). There was agreement about the degree of stenosis in 90% of the cases. IVDSA grading was correct in 94% of atheromatous lesions and in 56% of the fibromuscular dysplastic lesions. In the high-grade atheromatous lesions, the degree of stenosis was slightly overestimated on IVDSA studies in 22.5% of the cases. In fibromuscular dysplasia, stenosis was underestimated in 33% of the cases.     

PGD for a complex chromosomal rearrangement by array comparative genomic hybridization

Patients carrying a chromosomal rearrangement (CR) have an increased risk for chromosomally unbalanced conceptions. Preimplantation genetic diagnosis (PGD) may avoid the transfer of embryos carrying unbalanced rearrangements, therefore increasing the chance of pregnancy. Only 7-12 loci can be screened by fluorescence in situ hybridization whereas microarray technology can detect genome-wide imbalances at the single cell level. We performed PGD for a CR carrier with karyotype 46,XY,ins(3;2)(p23;q23q14.2),t(6;14)(p12.2;q13) using array comparative genomic hybridization. Selection of embryos for transfer was only based on copy number status of the chromosomes involved in both rearrangements. In two ICSI-PGD cycles, nine and seven embryos were analysed by array, leaving three and one embryo(s) suitable for transfer, respectively. The sensitivity and specificity of single cell arrays was 100 and 88.8%, respectively. In both cycles a single embryo was transferred, resulting in pregnancy following the second cycle. The embryo giving rise to the pregnancy was normal/balanced for the insertion and translocation but carried a trisomy 8 and nullisomy 9 in one of the two biopsied blastomeres. After 7 weeks of pregnancy the couple miscarried. Genetic analysis following hystero-embryoscopy showed a diploid (90%)/tetraploid (10%) mosaic chorion, while the gestational sac was empty. No chromosome 8 aneuploidy was detected in the chorion, while 8% of the cells carried a monosomy for chromosome 9. In summary, we demonstrate the feasibility and determine the accuracy of single cell array technology to test against transmission of the unbalanced meiotic products that can derive from CRs. Our findings also demonstrate that the genomic constitution of extra-embryonic tissue cannot necessarily be predicted from the copy number status of a single blastomere.