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L Thijs

Publications and source records attributed to L Thijs.

At least 19 recordsLinked to original sources
PubMed2006

Blood pressure and urinary sodium excretion in relation to the A-1984G adrenomedullin polymorphism in a Chinese population.

Adrenomedullin (ADM) is a vasodilator and inhibits salt appetite. An A-to-G substitution at position -1984 in the promoter region of the ADM gene likely increases transcription. We therefore investigated this polymorphism in relation to blood pressure and urinary sodium in a Chinese population. We genotyped 427 Chinese enrolled in a family-based population study. We measured blood pressure by conventional sphygmomanometry and ambulatory monitoring. The frequencies of the ADM AA, AG, and GG genotypes were 50.6, 38.2, and 11.2%, respectively. In adjusted analyses, G allele carriers, compared to AA homozygotes, had significantly lower conventional (45.3 versus 48.5 mm Hg, P = 0.004) and 24-h (42.6 versus 44.3 mm Hg, P = 0.03) pulse pressures and urinary sodium excretion (143.8 versus 159.4 mmol/day, P = 0.03). In parents, but not offspring, both systolic pressure and pulse pressure were significantly (P<0.01) lower in G allele carriers. The genotypic difference in sodium excretion was consistent across the age range. In 68 informative offspring, transmission of the G allele was associated with lower urinary sodium excretion (effect size, 40.1 mmol/day, P = 0.01). In 81 healthy volunteers, the plasma ADM concentration was 15.2% higher in GG homozygotes than in sex- and age-matched AA subjects (11.4 versus 9.9 pmol/l, P = 0.10). In conclusion, in Chinese, the ADM -1984G allele is associated with lower sodium excretion and in older subjects also with lower systolic pressure and narrower pulse pressure.

Adrenomedullin↗
PubMed2004

Should pulse pressure become part of the Framingham risk score?

An increased pulse pressure suggests aortic stiffening. New evidence also suggests that pulse pressure is a more sensitive measure of risk than other indexes of blood pressure in middle-aged and older persons. The objective of the study was to relate pulse pressure to the risk of cardiovascular events in the general population, and to assess whether pulse pressure could improve the Framingham risk prediction. A total of 378 men and 391 women over the age of 50 years (mean 62.7 years) were followed. Sex-specific Framingham cardiovascular risk scores were derived from age, systolic pressure, diastolic pressure, total and HDL cholesterol, smoking status and the presence or absence of diabetes mellitus. The cutoff points used to develop a pulse pressure score were calculated by determining the percentile points corresponding to the blood pressure categories in the Framingham risk score. We calculated relative hazard rates by multiple Cox regression. After a median follow-up of 7.2 years (range: 11 months-15 years), a total of 148 cardiovascular events occurred. In Cox regression analysis, a 10 mmHg higher pulse pressure was associated with 31% (P<0.0001) increase in the risk for cardiovascular events (fatal and nonfatal) after adjustment for sex, age, total and HDL cholesterol, smoking and the presence of diabetes mellitus. After adjustment for the aforementioned risk factors, a one-point increment in the blood pressure and pulse pressure scores was associated with a 40 and 48% (both P<0.0001) increase in the risk of fatal and nonfatal cardiovascular events, respectively. When both the blood pressure and pulse pressure scores were forced into a Cox model, only the pulse pressure score remained statistically significant (P<0.0001) with a relative hazard rate of 1.37 (CI: 1.16-1.69). These prospective data suggest that pulse pressure may improve the Framingham risk prediction among middle-aged and older individuals. Further studies, especially in the Framingham cohort, are warranted.

Age Factors↗
PubMed2004

Determinants of white-coat hypertension.

BACKGROUND: The prevalence of white-coat hypertension (WCH) is considerable in patients referred with elevated office blood pressure. Failure to recognise this phenomenon can lead to the inappropriate use of antihypertensive medications. We undertook this study to determine the profile of patients with WCH. METHODS: Baseline clinic and daytime ambulatory blood pressures were available from 5716 patients referred over a 22-year period. Individuals were considered to have WCH if they had an elevated clinic blood pressure measurement greater than 140/90 mmHg and normal daytime mean ambulatory blood pressure. Mean age was 53.6 years and 53.2% were female. RESULTS: The overall prevalence of white-coat hypertension was 15.4%. A higher prevalence was seen amongst older adults, females, and non-smokers. CONCLUSION: Multivariate logistic regression analysis confirmed these characteristics as independent predictors of WCH.

Blood Pressure Determination↗
PubMed2002

An epidemiological re-appraisal of the association between blood pressure and blood lead: a meta-analysis.

Studies on the possible association between blood pressure and blood lead have reached divergent conclusions. In a previous meta-analysis, a doubling of the blood lead concentration was associated with a 1.0/0.6 mm Hg increase in systolic and diastolic blood pressure (BP). This meta-analysis updates the analysis originally performed in 1994. Articles on the association between BP and blood lead were identified from computer searches from January 1980 to February 2001 using the Medical Literature Analysis and Retrieval System. Of the studies reviewed, 31 provided sufficient details to be considered. The meta-analysis included 58518 subjects recruited from the general population in 19 surveys and from occupationally exposed groups in 12 studies. In all but four studies, the results were adjusted for age, and most studies took into account additional confounding factors such as body mass index and the use of alcohol and medication. Weighted joint P-values were calculated using Stouffer's procedure. The association between BP and blood lead was similar in both men and women. In the combined studies, a two-fold increase in blood lead concentration was associated with a 1.0 mm Hg rise in the systolic pressure (95% CI +0.5 to +1.4 mm Hg; P < 0.001) and with a 0.6 mm Hg increase in the diastolic pressure (95% CI +0.4 to +0.8 mm Hg; P < 0.001). On balance, this meta-analysis suggests that there can only be a weak association between BP and blood lead.

Adolescent↗
PubMed2001

Cardiovascular protection and blood pressure reduction: a meta-analysis.

BACKGROUND: Whether antihypertensive drugs offer cardiovascular protection beyond blood pressure lowering has not been established. We aimed to investigate whether pharmacological properties of antihypertensive drugs or reduction of systolic pressure accounted for cardiovascular outcome in hypertensive or high-risk patients. METHODS: In a meta-analysis we extracted summary statistics from published reports, and calculated pooled odds ratios for experimental versus reference treatment. We correlated across-trials odd ratios for differences in systolic pressure between groups. FINDINGS: We analysed nine randomised trials comparing treatments in 62605 hypertensive patients. Compared with old drugs (diuretics and b-blockers), calcium-channel blockers and angiotensin converting-enzyme inhibitors offered similar overall cardiovascular protection, but calcium-channel blockers provided more reduction in the risk of stroke (13.5%, 95% CI 1.3-24.2, p=0.03) and less reduction in the risk of myocardial infarction (19.2%, 3.5-37.3, p=0.01). Heterogeneity was significant between trials because of high risk of cardiovascular events on doxazosin in one trial, and high risk of stroke on captopril in another; but systolic pressure differed between groups in these two trials by 2-3 mm Hg. Similar systolic differences occurred in a trial of diltiazem versus old drugs, and in three trials of converting-enzyme inhibitor against placebo in high-risk patients. Meta-regression across 27 trials (136124 patients) showed that odds ratios could be explained by achieved differences in systolic pressure. INTERPRETATION: Our findings emphasise that blood pressure control is important. All antihypertensive drugs have similar long-term efficacy and safety. Calcium-channel blockers might be especially effective in stroke prevention. We did not find that converting-enzyme inhibitors or a-blockers affect cardiovascular prognosis beyond their antihypertensive effects.

Aged↗
PubMed2001

Renal function, cytogenetic measurements, and sexual development in adolescents in relation to environmental pollutants: a feasibility study of biomarkers.

BACKGROUND: Human exposure to chemicals is normally monitored by measurement of environmental pollutants in external media. We investigated whether biomarkers in adolescents can show exposure to, and health effects of, common environmental pollutants. METHODS: We recruited 200 17-year-old adolescents (120 girls) from a rural control area and from two suburbs polluted by a lead smelter and two waste incinerators. We measured biomarkers of exposure and of effect in blood and urine samples, and obtained questionnaire data. School doctors measured testicular volume and staged sexual maturation. FINDINGS: Internal exposure was mostly within current standards. Concentrations of lead and cadmium in blood, PCBs (polychlorinated biphenyls) and dioxin-like compounds in serum samples, and metabolites of VOCs (volatile organic compounds) in urine were higher in one or both suburbs than in the control area. Children who lived near the waste incinerators matured sexually at an older age than others, and testicular volume was smaller in boys from the suburbs than in controls. Biomarkers of glomerular or tubular renal dysfunction in individuals were positively correlated with blood lead. Biomarkers of DNA damage were positively correlated with urinary metabolites of PAHs (polycyclic aromatic hydrocarbons) and VOCs. Interpretation Biomarkers can be used to detect environmental exposure to pollutants and measure their biological effects before overt disease develops. Our findings suggest that current environmental standards are insufficient to avoid measurable biological effects.

Adolescent↗
PubMed2001

Polymer-aided stereodivergent synthesis (PASS): a new concept for the discrete preparation of optical antipodes.

[structure: see text]. A new concept for the discrete preparation of optical antipodes is reported. The approach makes use of a cyclization/cleavage procedure that has been applied to polymer-supported quasi-meso compound 1, containing a polymeric leaving group and a regular leaving group. Two-directional cyclization leads to the formation and separation of quasi-enantiomers 2 and 3 simultaneously, with one being immobilized and one free in solution. Treatment of 2 and 3 with appropriate nucleophiles gives discrete enantiomers 4 and 5.

Journal Article↗
PubMed2001

The pulse pressure-to-stroke index ratio predicts cardiovascular events and death in uncomplicated hypertension.

OBJECTIVES: The goal of this study was to assess the prognostic power of the pulse pressure-to-stroke index (PP-to-SVi) ratio for cardiovascular events and mortality in patients with uncomplicated hypertension. BACKGROUND: The prognostic significance of pulse pressure (PP) has been studied repeatedly, but few data are available on the PP-to-SVi ratio. METHODS: Invasive hemodynamic measurements, including brachial intra-arterial pressure and stroke index by the direct oxygen Fick method, were performed in the period 1972 to 1982 in 192 patients with uncomplicated hypertension; their outcome was ascertained in 1994. RESULTS: Age at baseline averaged 37 +/- 12 years; brachial artery pressure was 165 mm Hg +/- 30/89 +/- 17 mm Hg; PP averaged 76 mm Hg +/- 18 mm Hg, and the PP-to-SVi ratio was 1.67 mm Hg/(ml/m2) +/- 0.73 mm Hg/(ml/m2). During 3,057 patient years of follow-up, 19 patients died, and 44 experienced at least one fatal or nonfatal cardiovascular event. Cox regression analysis revealed that the PP-to-SVi ratio was a significant predictor of fatal and nonfatal cardiovascular events and of all-cause mortality after control for age and gender (p < 0.01). Its predictive power persisted after additional adjustment for mean arterial pressure and heart rate. Each 0.75-mm Hg/(ml/m2) increase in the PP-to-SVi ratio was independently associated with a 79% increase in the risk of a cardiovascular event (p = 0.01) and a 2.05-fold greater risk of all-cause mortality (p = 0.01). CONCLUSIONS: The PP-to-SVi ratio is a significant and independent predictor of cardiovascular events and mortality in selected patients with uncomplicated hypertension.

Adult↗
PubMed2001

A randomised, placebo-controlled, double-blind, crossover study of losartan and enalapril in patients with essential hypertension.

The primary objective of this randomised, placebo- controlled, double-blind, crossover study, was to evaluate and compare the longer term effects of the angiotensin II type 1 receptor antagonist losartan and the converting enzyme inhibitor enalapril on 24-h ambulatory blood pressure (BP). After a 4-week placebo run-in period, nine patients with essential hypertension entered the double-blind phase of the study, which consisted of three 6-week periods during which patients were treated with placebo, enalapril 20 mg o.d. or losartan 50 mg o.d. Losartan and enalapril, taken between 07.00 and 08.00, reduced ambulatory BP throughout the 24-h period. Average night time BP was reduced from 133/85 mm Hg on placebo to 124/78 mm Hg on enalapril and to 126/77 mm Hg on losartan. Daytime BP averaged 157/101 mm Hg on placebo, and was significantly lower during enalapril (142/91 mm Hg) than during losartan treatment (147/95 mm Hg). Clinic BP, measured 2 to 4 hours after drug intake, was reduced to the same extent by both drugs. The losartan-induced BP changes were significantly related to those obtained with enalapril (0.63 < r < 0.93). Ambulatory BP monitoring was repeated after 4 weeks of combined therapy in six patients. The BP lowering effect of the combination was not significantly better than that achieved with enalapril alone. In conclusion, losartan 50 mg o.d. and enalapril 20 mg o.d. lower BP to approximately the same extent, except for a more pronounced effect of enalapril on daytime ambulatory BP. The current study does not provide convincing evidence that addition of losartan to enalapril in the doses used further reduces BP.

Adult↗
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.

Aged↗
PubMed2001

Risk and benefit of treatment of isolated systolic hypertension in the elderly: evidence from the Systolic Hypertension in Europe Trial.

The Syst-Eur trial investigated whether active treatment starting with the dihydropyridine calcium channel blocker (CCB) nitrendipine, could reduce the cardiovascular complications of isolated systolic hypertension (ISH) in the elderly. The intention-to-treat analysis showed that active treatment improved outcome. The per-protocol analysis largely confirmed these results. The effect of treatment on total and cardiovascular mortality might be attenuated in very old patients. Further analysis also suggested benefit in those patients who remained on nitrendipine monotherapy. Active treatment was more beneficial in patients with diabetes as compared with those without diabetes at entry and reduced the incidence of dementia by 50%. Analyses of data from the Ambulatory Blood Pressure Monitoring (ABPM) Side Project suggested that most of the benefit of treatment was seen in patients with a daytime systolic BP > or = 160 mm Hg. Finally, a meta-analysis partly based on Syst-Eur data showed that in older hypertensive patients pulse pressure and not mean pressure is the major determinant of cardiovascular risk.

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

Dihydropyridine calcium-channel blockers for antihypertensive treatment in older patients--evidence from the Systolic Hypertension in Europe Trial.

OBJECTIVE: The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension. DESIGN: Randomised, placebo-controlled, double-blind outcome trial. SETTING: Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries. SUBJECTS: Patients aged > or = 60 years with sitting systolic blood pressure (BP) 160-219 mmHg and sitting diastolic BP < 95 mmHg during run-in phase. METHODS AND RESULTS: Four thousand, six hundred and ninety-five patients were randomly assigned to active treatment (N = 2,398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or to matching placebos (N = 2,297). In the intention-to-treat analysis, the between-group difference in blood pressure (BP) amounted to 10.1/4.5 mmHg (P < 0.001). Active treatment reduced the incidence of fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.003). On active treatment all cardiac endpoints decreased by 26% (P = 0.03) and all cardiovascular endpoints by 31% (P < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, P = 0.07), but all-cause mortality was not influenced (-14%, P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic BP at entry (P = 0.05). The benefits of active treatment were not independently related to sex or to the presence of cardiovascular complications at entry. The antihypertensive regimen was more effective in patients with diabetes than in those without diabetes at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. Active treatment reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05) and all cardiovascular endpoints by 32% (P < 0.001). Total mortality was reduced by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not reach statistical significance in this analysis. Compared with placebo, active treatment also reduced the incidence of dementia by 50%. CONCLUSION: Stepwise antihypertensive drug treatment, starting with the dihydropiridine calcium-channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.

Aged↗
PubMed2000

Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. METHODS AND RESULTS: Patients who were >/=60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (>/=160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P<0.001) and, during follow-up, a lower incidence of stroke (P<0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P<0.001). The influence of active treatment on ECG voltages (P<0.05) and on the incidence of stroke (P<0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. CONCLUSIONS: Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.

Aged↗
PubMed2000

Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients.

BACKGROUND: Current guidelines for the management of hypertension rest almost completely on the measurement of systolic and diastolic blood pressure. However, the arterial blood pressure wave is more correctly described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. OBJECTIVE: To explore the independent roles of pulse pressure and mean pressure as determinants of cardiovascular prognosis in older hypertensive patients. METHODS: This meta-analysis, based on individual patient data, pooled the results of the European Working Party on High Blood Pressure in the Elderly trial (n = 840), the Systolic Hypertension in Europe Trial (n = 4695), and the Systolic Hypertension in China Trial (n = 2394). The relative hazard rates associated with pulse pressure and mean pressure were calculated using Cox regression analysis, with stratification for the 3 trials and with adjustments for sex, age, previous cardiovascular complications, smoking, and treatment group. RESULTS: A 10-mm Hg wider pulse pressure increased the risk of major cardiovascular complications; after controlling for mean pressure and the other covariates, the increase in risk ranged from approximately 13% for all coronary end points (P = .02) to nearly 20% for cardiovascular mortality (P = .001). In a similar analysis, mean pressure predicted the incidence of cardiovascular complications but only after removal of pulse pressure as an explanatory variable from the model. Furthermore, the probability of a major cardiovascular end point increased with higher systolic blood pressure; at any given level of systolic blood pressure, it also increased with lower diastolic blood pressure, suggesting that the wider pulse pressure was driving the risk of major complications. CONCLUSIONS: In older hypertensive patients, pulse pressure not mean pressure is the major determinant of cardiovascular risk. The implications of these findings for the management of hypertensive patients should be further investigated in randomized controlled outcome trials in which the pulsatile component of blood pressure is differently affected by antihypertensive drug treatment.

Aged↗
PubMed2000

Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials.

BACKGROUND: Previous meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertension METHODS: Patients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 x 2 contingency tables after application of Zelen's test of heterogeneity. FINDINGS: In eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor. Active treatment reduced total mortality by 13% (95% CI 2-22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18 vs 38), at or above age 70 (19 vs 39), and in patients with previous cardiovascular complications (16 vs 37). INTERPRETATION: Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.

Aged↗