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Biomedical subjects

W H Birkenhäger

Publications and source records attributed to W H Birkenhäger.

At least 19 recordsLinked to original sources
PubMed2004

Blood pressure and dementia.

Hypertension has proven to be a major predisposing factor for the development of both vascular and degenerative (Alzheimer's) dementias, either following stroke or gradually through more insidious microcerebrovascular processes. In the latter case the interval between the respective manifestations of hypertension and dementia may vary between a few years and several decades. The temporal relationships may become complicated by the finding that blood pressure tends to fall shortly before the onset of overt Alzheimers' disease. Whether or not timely antihypertensive regimens may delay or even prevent the development of dementias later in life is still an ''educated'' guess, as long there has been no comprehensive trial comparing the potential of the different antihypertensive drug classes in this regard. Until then, the class of dihydropyridine calcium antagonists (exemplified by nitrendipine in the Syst-Eur trial) is the only category having statistically been proven to be of substantial value for prevention of Alzheimer's disease.

Aged↗
PubMed2003

[Treating hypertension is more important than the choice of agent; results from the largest clinical trial until now].

During the past few years, several randomised trials have compared the effects of older blood-pressure lowering drugs (diuretics, beta-blockers) with those of newer ones (angiotensin converting enzyme (ACE) inhibitors, calcium entry blockers) on the long-term prognosis. In general, no significant differences were found between these regimes. Recently, the ALLHAT trial, which was the largest hypertension trial ever and in which over 40,000 patients with hypertension participated, was completed. The initial treatment consisted of either the diuretic chlorthalidone, the calcium entry blocker amlodipine, the ACE inhibitor lisinopril, or the alpha-blocker doxazosin. The latter arm was prematurely discontinued because of a higher incidence of the secondary endpoint heart failure and stroke. Based on an intention-to-treat analysis, the other types of treatment proved to be equivalent in terms of the primary endpoint, a composite of fatal coronary heart disease and non-fatal myocardial infarction. Although the investigators conclude that ALLHAT suggests that thiazide diuretics should be first choice in the treatment of hypertension, there are several caveats that tend to lessen the strength of this conclusion.

Adrenergic beta-Antagonists↗
PubMed2002

['Survival of the fittest': effect of regular physical exercise on health and life expectancy].

According to the 'Australian burden of disease study', physical inactivity appears to be a leading risk factor in the population at large, accounting for no less than 6.7% of the total loss of disability-adjusted life years. In women it is even the most important risk factor. Regular physical mobility and exercise can reduce this negative influence. The effects are: improvement of cardiovascular fitness, prevention of coronary events, and the reduction of excess mortality. The mortality risk may be reduced by 47% by physical activity, depending on the energy expenditure. Especially the studies of the last two years have so convincingly proven a robust effect of daily physical exercise that on this point permissiveness is no longer acceptable in the advice to the population at large.

Cardiovascular Diseases↗
PubMed2001

Blood pressure, cognitive functions, and prevention of dementias in older patients with hypertension.

The prevalence and incidence of degenerative and vascular dementias increase exponentially with age, from 70 years onward. In view of the increasing longevity of humans, both varieties are bound to evolve into a major problem worldwide. According to several longitudinal studies, hypertension appears to predispose individuals to the development of cognitive impairment and ensuing dementia, after a period varying from a few years to several decades. Antihypertensive drug treatment, according to preliminary evidence, may serve to reduce the rates of such events. Such findings await to be confirmed by formal therapeutic trials against a backdrop of "historical" observational sources.

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PubMed2001

The elderly hypertensive; cardiovascular and neurohormonal profile.

In this paper, a brief review is presented on the hemodynamic and neurohormonal changes in the elderly hypertensive patient. Arterial stiffening leads to a predominant rise in systolic pressure and a widening of pulse pressure. This in itself contributes to an increased cardiovascular risk in the elderly. In addition, there is a progressive decline in renal perfusion with, later on, a fall in glomerular filtration rate. The renal vascular changes may impair the kidney's ability to adequately maintain sodium balance under conditions of salt loading or restriction. The neurohormonal alterations generally include suppression and reduced responsiveness of the renin system and a decline in sympathetic activity.

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PubMed2001

Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial.

OBJECTIVE: To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs (NSAID) and outcome, in particular (gastrointestinal) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives. METHODS: Eligible patients (> or = 60 years, with systolic blood pressure 160-219 mm Hg and diastolic blood pressure < 95 mm Hg) were randomised to active treatment or placebo. Active treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg. Patients never taking NSAIDs (n = 2882) were compared with patients on chronic NSAID intake (n = 861), defined as reporting NSAID intake on at least 50% of the patient forms. RESULTS: There was a tendency towards lower mortality (relative hazard rate (95% confidence interval (CI), 0.77 (0.56-1.06)) and higher incidence of bleeding (1.13 (0.63-2.05) with chronic NSAID intake. Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points, chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo (P-value of the interaction term = 0.07). CONCLUSION: The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo. However, chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo.

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PubMed2001

Renal function in relation to three candidate genes.

We recently found that femoral intima media thickness, as well as the incidence of hypertension, is influenced by genes encoding the angiotensin-converting enzyme (ACE; insertion/deletion [I/D]) polymorphism, alpha-adducin (Gly460Trp), and aldosterone synthase (-344C/T). By interfering with blood pressure or sodium homeostasis, these genetic polymorphisms also may change renal function. We therefore investigated serum creatinine level, calculated and measured creatinine clearances, and 24-hour urinary protein excretion in subjects previously genotyped for these three polymorphisms. The 1,454 participants drawn at random from the population (64.3% of those invited) were aged 43.4 years and included 744 women (51.2%). Blood pressure, measured by study nurses at subjects' homes, averaged 123/76 mm Hg. Mean values were 90 micromol/L for serum creatinine; 84 and 88 mL/min/1.73 m(2) for calculated and measured (n = 855) creatinine clearances, respectively; and 90 mg/d of protein for proteinuria (n = 556). The prevalence of mild renal dysfunction (creatinine clearance </= 60 mL/min/1.73 m(2)) was nearly 11%. In single-gene analyses with adjustment for significant covariables, the risk for mild renal dysfunction was positively associated with the ACE D allele. However, multiple-gene analyses showed that these associations were restricted to carriers of the mutated alpha-adducin Trp allele (40.1% of all subjects). Findings remained similar after hypertensive patients and women on hormonal therapy were excluded. In this phenotypically more homogeneous subgroup, serum creatinine level was 3.6 micromol/L (P = 0.02) and relative risks for mild renal dysfunction and proteinuria were 1.7-fold (P < 0.001) and 26% (P = 0.02) greater in ACE D subjects than ACE II homozygotes, respectively. The aldosterone synthase T allele did not strengthen genetic associations with the ACE D allele considered alone or in combination with the alpha-adducin Trp allele. Thus, in the present cross-sectional analysis, renal function was slightly but consistently impaired when both the ACE D and alpha-adducin Trp alleles were present. These findings, together with experimental studies and our previous reports on femoral intima media thickness and the incidence of hypertension, constitute a growing body of evidence delineating a clinical entity genetically determined by the risk-carrying ACE D and alpha-adducin Trp alleles.

Adolescent↗
PubMed2001

The older hypertensive.

In this review the hypertensive status in older subjects is briefly examined from a diversity of angles: epidemiological/semiotic; pathophysiological (including haemodynamic/vascular, renal and neurohormonal features); components of blood pressure as separate cardiovascular risk factors in their own right, results of randomized trials comparing active with placebo treatment and comparing different active regimens (including diabetics as a subgroup with excessive risk); and, finally, modalities of treatment with a view on quality of life.

Age Factors↗
PubMed2001

Follow-up of renal function in treated and untreated older patients with isolated systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: In the outcome trials that provided information on renal function in older hypertensive patients, diuretics and beta-blockers were mostly used as first-line drugs. The long-term renal effects of calcium-channel blockers remain unclear. OBJECTIVE: To compare the changes in renal function in 2,258 treated and 2,148 untreated patients with isolated systolic hypertension, of whom 455 had diabetes mellitus and 390 had proteinuria. METHODS: We performed a post-hoc analysis of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Active treatment was initiated with nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mmHg, to less than 150 mmHg. The main outcome measures were serum creatinine concentration and creatinine clearance calculated by the formula of Cockroft and Gault. RESULTS: Serum creatinine concentration at the time when participants were randomly allocated to study groups was less than 176.8 micromol/l (2.0 mg/dl), averaging 88 micromol/l. At the time of the last serum creatinine measurement, the blood pressure difference (P< 0.001) between the two groups was 11.6/4.1 mmHg. In the intention-to-treat analysis (11,427 patient-years), serum creatinine and the calculated creatinine clearance were not influenced by active treatment. However, in the patients assigned randomly to receive active treatment, the incidence of mild renal dysfunction (serum creatinine at least 176.8 mmol/l) decreased by 64% (P= 0.04) and that of proteinuria by 33% (P= 0.03). Active treatment reduced the risk of proteinuria more in diabetic than in non-diabetic patients: by 71%, compared with 20% (P= 0.04). In non-proteinuric patients, active treatment did not influence serum creatinine, whereas in patients with proteinuria at entry to the study, serum creatinine decreased on active treatment (P< 0.001). Furthermore, in on-randomized treatment comparison stratified for risk at baseline, serum creatinine concentration did not change (P= 0.98) in patients continuing to receive monotherapy with nitrendipine, whereas it increased by 6.73 mmol/l (P < 0.001) in patients who received hydrochlorothiazide alone or in combination with other study medication (P < 0.001 for difference in trends). CONCLUSIONS: In older patients with isolated systolic hypertension, antihypertensive treatment starting with the dihydropyridine calcium-channel blocker, nitrendipine, did not decrease blood pressure at the expense of renal function and prevented the development of proteinuria, especially in diabetic patients.

Aged↗
PubMed2001

Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population.

BACKGROUND: The genes encoding angiotensin converting enzyme (ACE, I/D), alpha-adducin (ADD, Gly460Trp) and aldosterone synthase (AS, -344C/T) share the potential of influencing blood pressure (BP) via sodium homeostasis. However, most studies in humans focused on single-gene effects and disregarded epistasis, the suppression or potentiation of a gene by other non-allelic genes. METHODS: We studied the singular and combined effects of the aforementioned candidate genes: (1) in relation to BP, plasma renin activity (PRA) and urinary aldosterone in 1461 subjects randomly selected from a Caucasian population; and (2) in relation to the incidence of hypertension in a subgroup of 678 initially normotensive subjects followed up for 9.1 years (median). RESULTS: In cross-sectional analyses, AS/CC homozygosity was associated with slightly lower systolic BP (-1.32 mmHg; P = 0.08). AS/TT homozygotes showed both lower PRA and higher urinary aldosterone excretion (P < or = 0.05). In multiple-gene analyses, compared with the whole study population, ADD/Trp subjects had a higher relative risk of hypertension in the presence of the AS/T allele (1.29; P = 0.05), whereas in combination with AS/CC homozygosity ADD/Trp subjects had the smallest relative risk (0.48; P = 0.003). Hypertension developed in 229 subjects (36.6 cases per 1000 person-years). ACE/DD homozygosity, in comparison with the other ACE genotypes, was associated with increases in the incidence of hypertension, which amounted to 31% (P = 0.005) in single-gene analyses, to 59% (P = 0.004) in carriers of the ADD/Trp allele and to 122% (P = 0.0007) in AS/CC subjects. Among subjects who had both the ADD/Trp allele and the AS/CC genotype, ACE/DD homozygotes manifested a 252% (P = 0.001) higher incidence of hypertension. CONCLUSIONS: Epistatic interactions between the ACE, ADD and AS genes contribute to the prevalence and incidence of hypertension in Caucasians. The clinical relevance of the risk-conferring haplotypes identified in our prospective study was underscored by their positive predictive values, which under the assumption of a 20% life-time risk of hypertension, ranged from 29.8-40.1%.

Adult↗
PubMed2001

Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension.

We examined the relation of serum creatinine and uric acid to mortality and cardiovascular disease in older (aged >/=60 years) Chinese patients with isolated systolic hypertension (systolic/diastolic blood pressure >/=160/<95 mm Hg). We used Cox regression to correlate outcome with baseline serum creatinine and uric acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in the placebo-controlled Systolic Hypertension in China (Syst-China) TRIAL: Median follow-up was 3 years. In multiple Cox regression analysis with adjustment for gender, age, active treatment, and other significant covariates, serum creatinine was significantly associated with a worse prognosis. The relative hazard rates (95% CIs) associated with a 20-micromol/L increase in serum creatinine for all-cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27, P=0.003), 1.15 (1.01 to 1.31, P=0.03), and 1.37 (1.13 to 1.65, P=0.001), respectively. In a similar analysis, which also accounted for serum creatinine, serum uric acid was also significantly and independently associated with excess mortality of cardiovascular disease and stroke. The relative hazard rates associated with a 50-micromol/L increase of serum uric acid were 1.14 (1.02 to 1.27, P=0.02) for cardiovascular mortality and 1.34 (1.14 to 1.57, P<0.001) for fatal stroke. In conclusion, in older Chinese patients with isolated systolic hypertension, serum creatinine and serum uric acid were predictors of mortality.

Age Factors↗
PubMed2000

[Cognitive impairment and dementia in hypertension; the effect of antihypertensive medication].

The prevalence and incidence of both degenerative (Alzheimer) and vascular dementias rise exponentially with aging. In both forms of dementia hypertension is a predisposing factor. The interval between the onset of hypertension and the manifestation of dementia amounts to 12-15 years. A complicating factor is the observation that initial dementia may be accompanied by secondary decrease in blood pressure. A preventive effect of current antihypertensive treatment is likely, according to preliminary evidence (particularly with regard to the use of the calcium antagonist nitrendipine), but the hopeful perspective of protection against dementias through antihypertensive treatment remains to be confirmed by further prospective comparative trials.

Antihypertensive Agents↗
PubMed2000

[Use of angiotensin-II-antagonists in hypertension].

Angiotensin-II antagonists act on the terminus of the renin-angiotensin cascade, i.c. the angiotensin II subtype I (AT1) receptor. As a result, the receptor is reversibly blocked for the action of circulating angiotensin II, usually for 24 hours after a single dose. The consequence of this is that the blood pressure decreases, to the extent that this is dependent upon the action of this hormone. This action has various components, namely, vasoconstriction, sodium retention (mainly via aldosterone) and the promotion of cell growth in the cardiovascular system. The decrease in blood pressure is comparable to that achieved with the conventional antihypertensive drugs. The most striking difference is the almost total absence of the adverse effects know to be produced by the established agents. In vivo, there is no significant difference between the activity of the various AT1-receptor blockers. Their ultimate effect on the cardiovascular prognosis in the hypertensive population is still under investigation.

Angiotensin II↗
PubMed2000

Benefit of antihypertensive treatment in the diabetic patients enrolled in the Systolic Hypertension in Europe (Syst-Eur) trial.

In this review we attempt to determine the role of calcium channel blockers in preventing cardiovascular sequelae in patients with both hypertension and diabetes mellitus. The data have been collected from three sources: post-hoc analyses of subgroups of diabetic patients in placebo-controlled hypertension trials (SHEP, Syst-Eur, Syst-China); stepped-care blood pressure-oriented trials (HOT); and comparative trials focusing primarily on metabolic aspects and intermediate endpoints (ABCD, FACET). On balance, the data seem to indicate that long-acting calcium channel blockers score remarkably well in preventing cardiovascular complications in diabetic hypertensive patients.

Antihypertensive Agents↗
PubMed1999

Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

BACKGROUND: Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients. METHODS: After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, > or =60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placebo tablets were administered similarly. RESULTS: At randomization, 492 patients (10.5 percent) had diabetes. After a median follow-up of two years, the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg, respectively, among the diabetic patients. Among the 4203 patients without diabetes, systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg, respectively, in the two groups. After adjustment for possible confounders, active treatment was found to have reduced overall mortality by 55 percent (from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients), mortality from cardiovascular disease by 76 percent, all cardiovascular events combined by 69 percent, fatal and nonfatal strokes by 73 percent, and all cardiac events combined by 63 percent in the group of patients with diabetes. Among the nondiabetic patients, active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent. In the group of patients receiving active treatment, reductions in overall mortality, mortality from cardiovascular disease, and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients (P=0.04, P=0.02, and P=0.01, respectively). CONCLUSIONS: Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension. Thus, our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients.

Aged↗