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J G Wang

Publications and source records attributed to J G Wang.

At least 37 records · Page 2Linked to original sources
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

Experience in the United States with intact abdominal aortic aneurysm repair.

OBJECTIVES: The purpose of this study was to determine the current outcome in the United States and to identify predictors of mortality and "bad outcome" after open, intact abdominal aortic aneurysm (AAA) repair. METHODS: In a retrospective analysis, data were obtained from the Nationwide Inpatient Sample during 1994-1996. The Nationwide Inpatient Sample is a 20% all-payer stratified sample of nonfederal United States hospitals. Patients older than 49 years were identified by the presence of primary diagnostic (441.4-intact AAA) and procedure (38.44-resection of abdominal aorta with replacement) codes of the International Classification of Diseases, Ninth Revision (ICD-9 ). In-hospital mortality rate, discharge disposition, bad outcome (death or discharge to an institution), complications (ICD-9 postoperative codes), length of stay, and charges were determined. The mortality rate and bad outcome were analyzed by the use of patient demographics (age, sex, race), patient comorbidities (ICD-9 diagnostic codes), calendar year, and hospital characteristics (size, location, teaching status) with univariate and multivariate analyses. RESULTS: We identified 16,450 intact AAAs repairs during the study years. The mean patient age was 72 +/- 7 (+/- SD) years, and most patients were male (79.7%) and white (94.6%). Most repairs were performed at large (67.3%), urban (92.5%), and nonteaching (66.7%) institutions. The in-hospital mortality rate was 4.2%, the overall complication rate was 32.4%, and 91.2% of patients were discharged home, whereas the bad outcome rate was 12.6%. The median length of stay was 8 days (mean, 10.0 +/- 8.1), and median hospital charges were $28,052 (mean, $35,681 +/- $33,006) in 1996 dollars. Multivariate analysis showed that the mortality rate (P <.05) increased with age (70-79 years, 1.8 odds ratio [OR] [95% CI, 1.4-2.3], > 79 years, 3.8 OR [95% CI, 2.9-4.9]), sex (female, 1.6 OR [95% CI, 1.3-1.9]), cerebral vascular occlusive disease (1.8 OR [95% CI, 1.3-2.5]), preoperative renal insufficiency (9.5 OR [95% CI, 7.7-11.7]), and more than three comorbidities (11.2 OR [95% CI, 3.6-35.4]). Multivariate analysis also showed that bad outcome was associated with the same variables in addition to hospital size (small/medium), year of procedure (1996), chronic obstructive pulmonary disease, and two to three comorbidities. CONCLUSIONS: Outcome after open repair of intact AAA across the United States is quite good. Older, sicker patients may benefit from nonoperative treatment or the potentially lower risk endovascular approaches.

Aged↗
PubMed2001

Risks of smoking in treated and untreated older Chinese patients with isolated systolic hypertension.

OBJECTIVES: To examine the health risks associated with smoking and blood pressure in Chinese hypertensive patients and to compare the benefit of antihypertensive drug treatment with the risk attributable to smoking. METHODS: We used multiple Cox regression to correlate outcome with blood pressure and smoking status in 2284 older (aged > or = 60 years) patients enrolled in the Systolic Hypertension in China (Syst-China) Trial (systolic/diastolic blood pressure > or = 160/< 95 mmHg). RESULTS: Median follow-up was 3.0 years. After adjustment for sex, age, active antihypertensive treatment and various entry characteristics, the relative hazard rates associated with smoking more than 20 cigarettes per day were 2.04 (P = 0.04), 4.66 (P < 0.001) and 4.74 (P = 0.002) for all-cause, noncardiovascular and cancer mortality, respectively. With similar adjustments applied, the relative hazard rates for total (fatal and non-fatal) stroke associated with smoking 10-20 and more than 20 cigarettes per day were 1.78 (P = 0.04) and 2.23 (P = 0.03), respectively. Furthermore, both smoking and systolic blood pressure were associated with higher risk of stroke. Compared with the overall risk in the whole group, treating 1,000 patients for 5 years prevented 40 [95% confidence interval (CI), 5-75] strokes in smokers as well as never smokers. Prognosis in never smokers and past smokers was similar. Quitting smoking had the potential to prevent 51 (95% CI, -21 to 122) strokes in untreated hypertensive patients and to prevent 45 (95% CI, - 14 to 104) additional strokes in treated patients, over and above the effects of antihypertensive treatment. If, in addition to stroke, non-cardiovascular mortality was also accounted for, the estimated absolute benefit of quitting smoking increased to 69 (95% CI, -18 to 155) and 97 (95% CI, 23-171) events in the untreated and the treated group, respectively. CONCLUSIONS: In elderly Chinese patients, smoking was a risk factor for all-cause, non-cardiovascular and cancer mortality, as well as fatal and non-fatal stroke. The potential benefits of antihypertensive treatment and quitting smoking were approximately similar. In our view, these findings are important in terms of public health policies and health economics.

Aged↗
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

Antihypertensive drug therapy in older patients.

Elevated pulse pressure is an important cardiovascular risk factor in the elderly, and it remains to be determined whether this can be reversed. Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mmHg or higher on repeated measurement. Absolute benefit is greater in men, in patients aged 70 years or more, and in those with previous cardiovascular complications or greater pulse pressure. In the recently published comparative trials blood pressure gradients largely accounted for most, if not all, of the differences in outcome. In hypertensive patients, calcium-channel blockers may offer greater protection against stroke than against myocardial infarction, resulting in an overall cardiovascular benefit similar to that provided by older drug classes. The hypothesis that angiotensin-converting enzyme inhibitors or alpha-blockers might influence outcome over and beyond that expected on the basis of their blood pressure lowering effects still remains to be proved.

Aged↗
PubMed2001

Role of alpha/beta interferon in Venezuelan equine encephalitis virus pathogenesis: effect of an attenuating mutation in the 5' untranslated region.

Venezuelan equine encephalitis virus (VEE) is an important equine and human pathogen of the Americas. In the adult mouse model, cDNA-derived, virulent V3000 inoculated subcutaneously (s.c.) causes high-titer peripheral replication followed by neuroinvasion and lethal encephalitis. A single change (G to A) at nucleotide 3 (nt 3) of the 5' untranslated region (UTR) of the V3000 genome resulted in a virus (V3043) that was avirulent in mice. The mechanism of attenuation by the V3043 mutation was studied in vivo and in vitro. Kinetic studies of virus spread in adult mice following s.c. inoculation showed that V3043 replication was reduced in peripheral organs compared to that of V3000, titers in serum also were lower, and V3043 was cleared more rapidly from the periphery than V3000. Because clearance of V3043 from serum began 1 to 2 days prior to clearance of V3000, we examined the involvement of alpha/beta interferon (IFN-alpha/beta) activity in VEE pathogenesis. In IFN-alpha/betaR(-/-) mice, the course of the wild-type disease was extremely rapid, with all animals dying within 48 h (average survival time of 30 h compared to 7.7 days in the wild-type mice). The mutant V3043 was as virulent as the wild type (100% mortality, average survival time of 30 h). Virus titers in serum, peripheral organs, and the brain were similar in V3000- and V3043-infected IFN-alpha/betaR(-/-) mice at all time points up until the death of the animals. Consistent with the in vivo data, the mutant virus exhibited reduced growth in vitro in several cell types except in cells that lacked a functional IFN-alpha/beta pathway. In cells derived from IFN-alpha/betaR(-/-) mice, the mutant virus showed no growth disadvantage compared to the wild-type virus, suggesting that IFN-alpha/beta plays a major role in the attenuation of V3043 compared to V3000. There were no differences in the induction of IFN-alpha/beta between V3000 and V3043, but the mutant virus was more sensitive than V3000 to the antiviral actions of IFN-alpha/beta in two separate in vitro assays, suggesting that the increased sensitivity to IFN-alpha/beta plays a major role in the in vivo attenuation of V3043.

5' Untranslated Regions↗
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↗
PubMed2001

Carotid and femoral artery stiffness in relation to three candidate genes in a white population.

Different genetic polymorphisms influence cardiovascular disease. We recently discovered a relationship between the intima-media thickness of the muscular femoral artery, but not the elastic common carotid artery, and the combined ACE (ACE, I/D), alpha-adducin (Gly460Trp),and aldosterone synthase (AS, C-344T) gene polymorphisms. To investigate the relationship between these polymorphisms and functional properties of the carotid artery and femoral artery, a sample of 756 subjects enrolled in a population study were genotyped for the presence of the ACE D, alpha-adducin 460Trp, and aldosterone synthase -344T alleles. Vessel wall properties were assessed using a vessel wall movement detector system in combination with applanation tonometry. Statistical analysis allowed for confounders and interaction among genes. Cross-sectional compliance of the common carotid artery was negatively associated with the ACE D allele. ACE II versus ACE DD homozygotes differed, expressed as a percentage of the population mean (7.0%; 95% confidence interval [CI], 1.6% to 12.4%; P=0.02). In multigene analysis, ACE DD subjects also deviated significantly from the population mean for the distensibility coefficient of the common carotid artery when carrying the AS/T allele (-5.5%; 95% CI, -9.3% to -1.7%; P<0.01), without a change in cross-sectional compliance. ACE DD subjects, when homozygote for alpha-adducin Gly460, had a lower femoral cross-sectional compliance (-10.4%; 95% CI, -1.9% to -18.9%; P<0.03) and a lower distensibility (-9.7%; 95% CI, -2.1% to -17.3%; P<0.02) compared with the population mean. These data show that functional large artery properties are influenced by the ACE I/D polymorphism. Cross-sectional compliance and distensibility coefficients are influenced by the ACE I/D genotype, but this influence depends on the vascular territory and genetic background.

Adolescent↗
PubMed2001

Improved outcomes with antihypertensive medication in the elderly with isolated systolic hypertension.

Isolated systolic hypertension affects over 15% of all individuals aged >60 years. In the elderly, systolic hypertension is a major modifiable cardiovascular risk factor. Systolic blood pressure (SBP) is associated with higher risk of an adverse outcome, whereas diastolic blood pressure (DBP) is inversely correlated with total mortality, independent of SBP, highlighting the role of pulse pressure as a risk factor. Three placebo-controlled outcome trials on antihypertensive drug treatment in older patients with isolated systolic hypertension have been published: the Systolic Hypertension in the Elderly Program (SHEP), the Systolic Hypertension in Europe (Syst-Eur) Trial and the Systolic Hypertension in China (Syst-China) Trial. These 3 trials demonstrated the benefit of antihypertensive drug treatment. A meta-analysis was performed by pooling the patients from these 3 trials with a subset of patients with isolated systolic hypertension from 5 other trials in the elderly. The pooled results of 15,693 older patients with isolated systolic hypertension prove that antihypertensive drug treatment isjustified if on repeated clinic measurements SBP is 160 mm Hg or higher.

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

Genetic polymorphisms in the renin-angiotensin system: relevance for susceptibility to cardiovascular disease.

The renin-angiotensin system plays an important role in the pathogenesis of cardiovascular disease. Cloning of the human genes coding for the angiotensin-converting enzyme, angiotensinogen, and angiotensin II type 1 receptor has led to the discovery of several polymorphisms, which may be implicated in the pathogenesis of cardiovascular disease. The deletion/insertion (D/I) polymorphism of the angiotensin-converting enzyme gene is associated with hypertension in men, left ventricular hypertrophy in untreated hypertensive patients, various atherosclerotic cardiovascular complications, and microvascular disorders. The M235T polymorphism of the angiotensinogen gene may be associated with a higher risk of hypertension. The A1166C polymorphism of the angiotensin II type 1 receptor gene is probably correlated with hypertension and through an epistatic interaction with the D/I polymorphism of the angiotensin-converting enzyme gene possibly also with coronary heart disease. Several other gene polymorphisms, in particular those in the promoter area of the angiotensinogen gene, have been studied in relation to cardiovascular disease. Based on the insights gained from the reports summarized in this review article, population-based genetic studies of nuclear families are currently being conducted in Belgium and in the People's Republic of China with blood pressure and hypertension as the main outcome variables.

Animals↗
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

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↗
PubMed2000

Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group.

BACKGROUND: In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group initiated the placebo-controlled Syst-China trial to investigate whether antihypertensive drug treatment could reduce the incidence of fatal and nonfatal stroke in older Chinese patients with isolated systolic hypertension. OBJECTIVES: To explore (1) whether the benefits of active treatment were evenly distributed across 4 strata, prospectively defined according to sex and previous cardiovascular complications, and (2) whether the morbidity and mortality results were influenced by age, level of systolic or diastolic blood pressure (BP), smoking or drinking habits, or diabetes mellitus at enrollment. METHODS: Eligible patients had to be 60 years or older with a sitting systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg. After stratification for center, sex, and previous cardiovascular complications, 1253 patients were assigned to active treatment starting with nitrendipine (10-40 mg/d), with the possible addition of captopril (12.5-50.0 mg/d), and/or hydrochlorothiazide (12.5-50 mg/d). In the 1141 control patients, matching placebos were used similarly. RESULTS: Male sex, previous cardiovascular complications, older age, higher systolic BP or lower diastolic BP, living in northern China, smoking, and diabetes mellitus significantly and independently increased the risk of 1 or more of the following end points: total or cardiovascular mortality, all fatal and nonfatal cardiovascular end points, all strokes, and all cardiac end points. In the placebo-control group diabetes raised the risk of all end points 2- to 3-fold (P< or =.05). However, active treatment reduced the excess risk associated with diabetes to a nonsignificant level (P values ranging from .12-.86) except for cardiovascular mortality (P = .04). Cox regression with adjustments applied for significant covariates suggested that active treatment may reduce total mortality more (P = .06) in women and stroke more (P = .07) in men and that it may provide better protection against cardiac end points in nonsmokers than smokers (P = .04). Otherwise, the benefits of active treatment were equally manifest, regardless of the enrollment characteristics of the patients, and regardless of whether active treatment consisted of only nitrendipine or of nitrendipine associated with other active drugs. CONCLUSIONS: In elderly Chinese patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improved prognosis. The benefit was particularly evident in diabetic patients; for cardiac end points it tended to be larger in nonsmokers. Otherwise, the benefit of active treatment was not significantly influenced by the characteristics of the patients at enrollment in the trial.

Aged↗
PubMed2000

Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis.

This meta-analysis attempted to derive pooled estimates for the putative association between echocardiographic or electrocardiographic left ventricular hypertrophy and the deletion/insertion (D/I) polymorphism of the angiotensin-I converting enzyme. Case-control studies were combined, using the Mantel and Haenszel approach. Joint P-values for continuous variables were calculated by Stouffer's method. Continuous measurements of left ventricular mass, which were reported in different units, were expressed on a percentage scale using the within-study mean of the II genotype as the denominator. The computerised database used for this analysis, included 28 reports with an overall sample size of 6638 subjects. The prevalence of the D allele was significantly lower in Japanese (37.2%) than in Caucasians (56.2%). A funnel plot including 12 case-control studies (4094 subjects) suggested that no publication bias was present. Overall, left ventricular hypertrophy was not associated with the D allele. Compared with the II genotype, the excess risks of left ventricular hypertrophy associated with DD and DI genotypes were only 14% (95% CI: 0.92-1.42; P = 0.23) and 5% (95% CI: 0.87-1.28; P = 0.61), respectively. However, the sensitivity analysis showed that in untreated hypertensive patients the DD genotype, compared with II homozygozity, was associated with a 192% (P = 0.002) higher risk of left ventricular hypertrophy. If left ventricular mass was analysed as a continuous trait across 23 studies (5438 subjects), overall no association with the D/I polymorphism was present. However, if untreated hypertensive patients were analysed separately, echocardiographic left ventricular mass was on average 10.1% (95% CI: 4.8-15.5%; P = 0.001) higher in DDhomozygotes than in the II reference group. Thus, in untreated hypertensive patients, in case-control studies as well as association studies, the D allele behaved as a marker for left ventricular hypertrophy. These findings support the hypothesis that the enhanced ACE activity associated with the D allele may promote left ventricular hypertrophy if a pathophysiologic process causing this disorder, remains unopposed by treatment.

Alleles↗