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Willem H Birkenhäger

Publications and source records attributed to Willem H Birkenhäger.

At least 19 recordsLinked to original sources
PubMed2004

Prognostic significance of electrocardiographic voltages and their serial changes in elderly with systolic hypertension.

The aim of the present study was to assess the prognostic value of ECG voltages at baseline and their serial changes during follow-up in a large prospective study with standardized follow-up and strictly defined end points. Patients who were 60 years old or older, with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe trial. Active treatment consisted of nitrendipine, which could be combined with or replaced by enalapril, hydrochlorothiazide, or both. At the end of the double-blind part of the trial (median follow-up, 2.0 years), follow-up was extended and all patients received active study drugs (median total follow-up, 6.1 years). Electrocardiography was performed at baseline and yearly thereafter. Electrocardiographic left ventricular mass was prospectively defined as the sum of 3 voltages (RaVL+SV1+RV5), which averaged 3.1+/-1.0 mV. The adjusted relative hazard rate, associated with a 1 mV higher sum at baseline, amounted to 1.10 and 1.15 for all-cause and cardiovascular mortality and to 1.21 and 1.18 for strokes and cardiac events, respectively (P< or =0.01 for all). A 1-mV decrease in electrocardiographic voltages during follow-up independently predicted a lower incidence of cardiac events (relative hazard rate: 0.86; P< or =0.05), but not of stroke or mortality. In conclusion, electrocardiographic voltages at baseline and their serial changes during follow-up predict subsequent events in older patients with systolic hypertension.

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PubMed2004

Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial.

BACKGROUND: To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years. METHODS: The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. RESULTS: Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. CONCLUSIONS: Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.

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PubMed2004

Dementia and antihypertensive treatment.

PURPOSE OF REVIEW: We present an updated overview on the long-term effects of hypertension on the occurrence of cognitive dysfunction and overt degenerative or vascular dementia later in life. The preventative effects of antihypertensive treatment in this regard are examined, with a focus on placebo-controlled, double-blind, randomized prospective trials. RECENT FINDINGS: The stereotypical straightforward linear relationship between mid-life hypertension and dementia later in life can no longer be considered strictly invariable. Successfully treated hypertensive patients who are still at risk for clinical dementia late in life may ultimately fare better in the presence of a slightly elevated rather than low systolic blood pressure. The mechanisms underlying this 'J-curve' phenomenon are currently being explored. Recently completed prospective randomized antihypertensive trials (Syst-Eur 2, PROGRESS and SCOPE) have yielded variable results, and merit cautious interpretation. SUMMARY: The incidence and prevalence of dementia are increasing exponentially worldwide, particularly in those older than 70 years. Because hypertension predisposes to dementia, therapeutic blood pressure titration should be maintained over the years, and intensified beyond 70 years in order to avoid over-treatment in the latter period.

Antihypertensive Agents↗
PubMed2003

Essential hypertension.

Hypertension is a frequent, chronic, age-related disorder, which often entails debilitating cardiovascular and renal complications. Blood pressure is usually noted in combination with other cardiovascular risk factors. Diagnosis of hypertension increasingly relies on automated techniques of blood pressure measurement. The pathophysiology of essential hypertension depends on the primary or secondary inability of the kidney to excrete sodium at a normal blood pressure. The central nervous system, endocrine factors, the large arteries, and the microcirculation also have roles in the disorder. Although monogenic forms of blood pressure dysregulation exist, hypertension mostly arises as a complex quantitative trait that is affected by varying combinations of genetic and environmental factors. Non-pharmacological strategies can reduce blood pressure. Antihypertensive drug treatment diminishes the complications of hypertension. The concept that a few major genes will provide the final clue to the pathogenesis of essential hypertension is an oversimplification that contradicts the heterogeneous nature of this disorder. Further integration of genetic, molecular, clinical, and epidemiological research could disclose subsets of patients in whom specific combinations of genetic and environmental factors raise blood pressure, and might lead to more individualised treatment.

Adolescent↗
PubMed2002

The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study.

BACKGROUND: After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. OBJECTIVE: To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. METHODS: Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. RESULTS: Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33). CONCLUSION: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

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PubMed2002

The effects of calcium channel blockers on cardiovascular outcomes: a review of randomised controlled trials.

The choice of antihypertensive treatment should be guided by evidence of a reduction in the risk of cardiovascular (CV) events and therefore improved long-term outcome. Using pre-determined criteria, ten randomised, controlled trials that assessed the effects of calcium channel blockers (CCBs) on CV events in patients with hypertension were identified. Six of them enrolled a relatively small number (< 1500) of hypertensive patients, whereas four of the studies were much larger (> 4500 patients). The smaller studies produced mixed findings, especially those trials where CCBs were compared with diuretics; this may reflect methodological limitations and the impact of random error. The results from the four larger studies produced a consistent message: long-acting CCBs such as nifedipine, administered in a gastro-intestinal-transport-system (GITS) formulation, nitrendipine and diltiazem, reduce CV morbidity and mortality in hypertensive patients. In the one study that specifically enrolled high-risk hypertensive patients, nifedipine GITS was as effective as diuretic therapy in reducing CV events, and in all four larger studies sub-group analyses showed that the benefits of these CCBs extend to hypertensive patients with diabetes. The available evidence supports the use of these long-acting CCBs as a first-line treatment option in hypertensive patients.

Calcium Channel Blockers↗
PubMed2002

Carotid and femoral intima-media thickness in relation to three candidate genes in a Caucasian population.

BACKGROUND: In a Caucasian population, the prevalence and incidence of hypertension, renal function and large artery stiffness were significantly correlated with polymorphisms in the genes encoding the angiotensin-converting enzyme (ACE I/D), aldosterone synthase (-C344T) and the cytoskeleton protein alpha-adducin (Gly460Trp). OBJECTIVE: This study investigated intima-media thickening, a precursor of atherosclerosis, in relation to these genetic polymorphisms. METHODS: Carotid and femoral intima-media thickness were assessed with a wall-track system in 380 subjects enrolled in a population study. Subjects were genotyped for the presence of the ACE D, aldosterone synthase -344T and alpha-adducin 460Trp alleles. The statistical analysis allowed for confounders, interactions among genes, and the non-independence of the phenotypes within families. RESULTS: The sample included 188 men (49.5%). Mean age was 39.8 years. Intima-media thickness of the carotid and femoral arteries averaged 575 and 719 microm, respectively. Intima-media thickness of the femoral-but not carotid-artery increased with the number of ACE D alleles. The effect of ACE genotype on femoral intima-media thickness was confined to carriers of the 460Trp allele and the -344T allele. Expressed as a percentage of the population mean, the mean differences between II and DD homozygotes averaged 13.4% (95% CI 5.6-21.2%) in all subjects, 21.2% (8.0-34.5%) in carriers of the 460Trp allele, 15.4% (4.1-26.8%) in carriers of the -344T allele, and 25.2% (10.7-39.7%) if the 460Trp and -344T alleles were both present. CONCLUSION: This study shows that a relationship exists between the intima-media thickness of the large muscular femoral artery and the ACE gene. This relationship is only apparent in the presence of either the alpha-adducin 460Trp or the aldosterone synthase -344T allele. These findings may have clinical implications for the assessment of genetic cardiovascular risk.

Adolescent↗
PubMed2002

Prognostic significance of renal function in elderly patients with isolated systolic hypertension: results from the Syst-Eur trial.

Several reports suggest that markers of renal function such as serum creatinine, serum uric acid, and urinary excretion of protein may be related to cardiovascular complications and mortality. This study analyzed the data from the Syst-Eur trial, which was a randomized, placebo-controlled, double-blind intervention trial in elderly patients with isolated systolic hypertension. The purpose was to evaluate whether serum levels of creatinine and uric acid and urinary protein excretion at entry are related to subsequent morbidity and mortality. Incidence rates of total mortality, cardiovascular mortality, stroke (fatal as well as nonfatal), coronary events, and all cardiovascular endpoints were calculated for each quintile of serum creatinine or serum uric acid or for each category of protein excretion (none, trace, and overt). Crude and adjusted relative hazard rates were also determined for each 20 micro M increase in serum creatinine, each 50 micro M increase in serum uric acid, and for each protein excretion category. Even when adjusted for age, gender, and various other covariates, serum creatinine was significantly associated with a worse prognosis. There was an U-shaped relationship between serum uric acid and total mortality, but otherwise no obvious relationships were detected between serum uric acid levels and complications when appropriate adjustments were made for confounding variables. Proteinuria at entry was a significant predictor of total mortality and all cardiovascular endpoints. It is concluded that higher levels of serum creatinine and trace or overt proteinuria are associated with an increased number of cardiovascular events and with a higher mortality in patients with isolated systolic hypertension.

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