Hypertension in the elderly: new and old evidence that treatment may benefit the old.

Hypertension is prevalent and remains an important risk factor in elderly and very elderly. Randomized controlled outcome trials have shown benefit of antihypertensive treatment in patients with systolic diastolic hypertension and in patients with isolated systolic hypertension, aged 60 years and over. More recently benefit has also been shown in octogenerians with hypertension. Overall there is no strong evidence that protection against major cardiovascular events afforded by different drug classes varies substantially with age. Finally, blood pressure lowering therapy also improves prognosis in hypertensive patients with type 2 diabetes.

Left ventricular strain and strain rate in a general population.

AIMS: Strain and strain rate (SR) are measures of deformation that reflect left ventricular (LV) function. To our knowledge, no previous study described these indexes in a general population. We therefore described peak-systolic strain and SR of the LV in the general population and derived diagnostic thresholds for these measurements in a healthy subgroup. METHODS AND RESULTS: In 480 subjects enrolled in a family-based population study (50.5% women; mean age, 50.5 years; 37.2% hypertensive), we measured: (i) end-systolic longitudinal strain and peak-systolic SR from the basal portion of the LV inferior and inferolateral free walls; (ii) radial deformation of the LV inferolateral wall. Longitudinal (mean, 22.9%) and radial (59.2%) strain and longitudinal (1.31 s(-1)) and radial (3.40 s(-1)) SR decreased with age (P

Effects of genetic variation in adducin on left ventricular diastolic function as assessed by tissue Doppler imaging in a Flemish population.

BACKGROUND: We investigated the possible association between left ventricular diastolic function and the ADD1 Gly460Trp and ADD3 IVS11 +386A>G polymorphisms alone and in combination. METHODS: In a family-based population study (473 subjects; 50.5% women; mean age 50.5 years), we measured early (Ea) and late (Aa) diastolic peak velocities of the mitral annulus by tissue Doppler imaging. In multivariate-adjusted analyses, we investigated phenotype-genotype associations, while accounting for confounders and family structure. RESULTS: Lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.51 vs. 1.40; P = 0.005) and was lower in ADD3 A allele carriers than in GG homozygotes (1.42 vs. 1.55; P = 0.005). The effects of ADD1 on the lateral Ea and Ea/Aa weakened with older age (P < 0.05). The best fitting model for lateral Ea and Ea/Aa included ADD1, ADD3, and the three-way interaction term of both genes with age. Below the age of 50 years, the lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.91 vs. 1.73; P = 0.006), particularly in the presence of ADD3 GG homozygosity (2.46 vs. 1.80; P = 0.0008). In older subjects, these phenotype-genotype associations were not significant (P > 0.20). Transmission of the ADD1 Trp allele to offspring was associated with higher lateral Ea (+0.91; P = 0.026) and Ea/Aa ratio (+0.23; P = 0.0008). CONCLUSION: Our population-based study demonstrated that left ventricular diastolic relaxation is modulated by genetic variation in ADD1 and ADD3. This association was more prominent in younger subjects in whom longstanding environmental factors and ageing are less likely to mask genetic effects.

On-treatment diastolic blood pressure and prognosis in systolic hypertension.

BACKGROUND: It has been suggested that low diastolic blood pressure (BP) while receiving antihypertensive treatment (hereinafter called on-treatment BP) is harmful in older patients with systolic hypertension. We examined the association between on-treatment diastolic BP, mortality, and cardiovascular events in the prospective placebo-controlled Systolic Hypertension in Europe Trial. METHODS: Elderly patients with systolic hypertension were randomized into the double-blind first phase of the trial, after which all patients received active study drugs (phase 2). We assessed the relationship between outcome and on-treatment diastolic BP by use of multivariate Cox regression analysis during receipt of placebo (phase 1) and during active treatment (phases 1 and 2). RESULTS: Rates of noncardiovascular mortality, cardiovascular mortality, and cardiovascular events were 11.1, 12.0, and 29.4, respectively, per 1000 patient-years with active treatment (n = 2358) and 11.9, 12.6, and 39.0, respectively, with placebo (n = 2225). Noncardiovascular mortality, but not cardiovascular mortality, increased with low diastolic BP with active treatment (P < .005) and with placebo (P < .05); for example, hazard ratios for lower diastolic BP, that is, 65 to 60 mm Hg, were, respectively, 1.15 (95% confidence interval, 1.00-1.31) and 1.28 (95% confidence interval, 1.03-1.59). Low diastolic BP with active treatment was associated with increased risk of cardiovascular events, but only in patients with coronary heart disease at baseline (P < .02; hazard ratio for BP 65-60 mm Hg, 1.17; 95% confidence interval, 0.98-1.38). CONCLUSIONS: These findings support the hypothesis that antihypertensive treatment can be intensified to prevent cardiovascular events when systolic BP is not under control in older patients with systolic hypertension, at least until diastolic BP reaches 55 mm Hg. However, a prudent approach is warranted in patients with concomitant coronary heart disease, in whom diastolic BP should probably not be lowered to less than 70 mm Hg.

Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension.

BACKGROUND: It is uncertain whether ambulatory blood-pressure measurements recorded for 24 hours in patients with treated hypertension predict cardiovascular events independently of blood-pressure measurements obtained in the physician's office and other cardiovascular risk factors. METHODS: We assessed the association between base-line ambulatory blood pressures in treated patients and subsequent cardiovascular events among 1963 patients with a median follow-up of 5 years (range, 1 to 66 months). RESULTS: We documented new cardiovascular events in 157 patients. In a Cox proportional-hazards model with adjustment for age, sex, smoking status, presence or absence of diabetes mellitus, serum cholesterol concentration, body-mass index, use or nonuse of lipid-lowering drugs, and presence or absence of a history of cardiovascular events, as well as blood pressure measured at the physician's office, higher mean values for 24-hour ambulatory systolic and diastolic blood pressure were independent risk factors for new cardiovascular events. The adjusted relative risk of cardiovascular events associated with a 1-SD increment in blood pressure was 1.34 (95 percent confidence interval, 1.11 to 1.62) for 24-hour ambulatory systolic blood pressure, 1.30 (95 percent confidence interval, 1.08 to 1.58) for ambulatory systolic blood pressure during the daytime, and 1.27 (95 percent confidence interval, 1.07 to 1.57) for ambulatory systolic blood pressure during the nighttime. For ambulatory diastolic blood pressure, the corresponding relative risks of cardiovascular events associated with a 1-SD increment were 1.21 (95 percent confidence interval, 1.01 to 1.46), 1.24 (95 percent confidence interval, 1.03 to 1.49), and 1.18 (95 percent confidence interval, 0.98 to 1.40). CONCLUSIONS: In patients with treated hypertension, a higher ambulatory systolic or diastolic blood pressure predicts cardiovascular events even after adjustment for classic risk factors including office measurements of blood pressure.

Incidence of cardiovascular events in white-coat, masked and sustained hypertension versus true normotension: a meta-analysis.

OBJECTIVE: To perform a meta-analysis on the incidence of cardiovascular events in white-coat hypertension (WCHT), masked and sustained hypertension in comparison with true normotension. METHODS: We searched for individual studies, in which the adjusted relative risk of incident cardiovascular events was assessed in patients with WCHT, masked and sustained hypertension versus normotension in the same study population. For each type of hypertension, the weighted overall hazard ratio (HR) and 95% confidence intervals (CI) were calculated. RESULTS: Seven studies were identified, involving a total of 11 502 participants. Four studies were performed in the population, two in primary care and one in specialist care. Two studies were exclusively on treated hypertensive patients; individuals on antihypertensive treatment were included in all the other studies except one. Cut-off blood pressure was 140/90 mmHg for office blood pressure in all studies and 135/85 mmHg (83 in one study) for out-of-office blood pressure. The average age of the study populations was 63 years; 53% were men. The endpoint consisted of cardiovascular death in one study and of various aggregates of fatal and non-fatal cardiovascular events in the others. During an average follow-up of 8.0 years, there were 912 first cardiovascular events. The overall adjusted HR versus normotension was 1.12 (95% CI 0.84-1.50) for WCHT (P = 0.59), 2.00 (1.58-2.52) for masked hypertension (P < 0.001), and 2.28 (1.87-2.78) for sustained hypertension (P < 0.001). CONCLUSION: The meta-analysis indicates that the incidence of cardiovascular events is not significantly different between WCHT and true normotension, whereas the outcome is worse in patients with masked or sustained hypertension.

Sympathetic activity, assessed by power spectral analysis of heart rate variability, in white-coat, masked and sustained hypertension versus true normotension.

OBJECTIVE: To assess, in a population-based approach, sympathetic nervous system activity by the use of power spectral analysis of heart rate variability, in normotension, white-coat hypertension, masked hypertension and sustained hypertension. METHODS: The electrocardiographic RR interval was registered in the supine and standing positions and the low-frequency and high-frequency components of its variability were quantified. Cut-off values of 140/90 mmHg for conventional blood pressure and 135/85 mmHg for daytime ambulatory blood pressure were used to define the four blood pressure groups. RESULTS: After exclusion of patients with diabetes, myocardial infarction or treated hypertension, 1485 subjects with complete data remained for the analysis in the supine position. Age averaged 39 +/- 14 years; 54% were women. Conventional and ambulatory blood pressure averaged, respectively, 122 +/- 16/79 +/- 11 mmHg and 124 +/- 12/77 +/- 8 mmHg. After adjusting for demographic, anthropometric and lifestyle characteristics, the low-frequency to high-frequency ratio (geometric mean) averaged 0.81 in normotension and was significantly higher in white-coat hypertension (1.11; P < 0.001), based on a higher low-frequency component and a lower high-frequency component (P < 0.01). This ratio was not significantly different between normotension, masked hypertension (0.97) and sustained hypertension (0.93). The adjusted standing-to-supine ratio of the high-frequency component (geometric mean) was significantly higher in sustained hypertension (0.50) than in normotension (0.39; P < 0.01), but not in white-coat (0.40) and masked hypertension (0.45). CONCLUSION: The findings at rest are compatible with increased sympathetic activity and decreased parasympathetic modulation in white-coat hypertension, with normal autonomic cardiac regulation in masked and sustained hypertension. In addition, sustained hypertension is characterized by a blunted decrease of the high-frequency component on standing.

Athletes with systemic hypertension.

Hypertension is rare in the young, but its prevalence increases with aging. Currently, about 25% of the population has hypertension and this is expected to increase to up to about 29% in 2025. The overall risk of the hypertensive patient depends not only on blood pressure but also on the presence of other cardiovascular risk factors, target organ damage, and associated clinical conditions. The recommendations for preparticipation screening, sports participation, and follow-up depend on the cardiovascular risk profile of the individual athlete. When antihypertensive treatment is required, calcium channel blockers and blockers of the renin-angiotensin system are currently the drugs of choice.

Progression to hypertension in the non-hypertensive participants in the Flemish Study on Environment, Genes and Health Outcomes.

OBJECTIVE: To evaluate the consistency between a randomly recruited Western European population and the participants of the Framingham Heart Study, with respect to the rates and determinants of progression to hypertension. METHODS: Among the non-hypertensive individuals enrolled in the Flemish Study on Environment, Genes and Health Outcomes, we assessed progression from optimal (< 120/80 mmHg), normal (120-129/80-84 mmHg) and high-normal (130-139/85-89 mmHg) blood pressure to hypertension (> or = 140/90 mmHg). Our analysis included 781 women and 675 men (age range 10-77 years) who were followed up for a median of 4.6 years (interquartile range 2.4-8.1 years). Our statistical methods included Kaplan-Meier survival function estimates, the log-rank test and multiple Cox regression. RESULTS: In individuals younger than 50 years, 4-year progression rates associated with optimal, normal and high-normal blood pressure were 7.4% [95% confidence interval (CI) 5.5-9.3], 17.9% (95% CI 14.3-21.6) and 24.5% (95% CI 18.7-30.2), respectively. Corresponding 4-year rates of progression for individuals aged 50 years or older were 16.4% (95% CI 11.2-22.5), 26.3% (95% CI 19.8-32.9) and 54.0% (95% CI 45.7-62.3), respectively. In multivariate Cox regression, blood pressure category and body mass index at baseline were strong predictors of hypertension. Before the age of 50 years, male sex and a fast heart rate were also forerunners of hypertension. CONCLUSIONS: The stepwise increase in incidence of hypertension across the three non-hypertensive blood pressure categories in our cohort was similar to that observed in the Framingham Heart Study. The Framingham findings, which have informed several guidelines, can be extrapolated to a Western European population.

Left ventricular hypertrophy is a predictor of cardiovascular events in elderly hypertensive patients: Hypertension in the Very Elderly Trial.

OBJECTIVE: We assessed the prognostic value of ECG left ventricular hypertrophy (LVH) using Sokolow-Lyon (SL-LVH), Cornell voltage (CV-LVH) or Cornell product (CP-LVH) criteria in 3043 hypertensive people aged 80 years and over enrolled in the Hypertension in the Very Elderly Trial. METHODS: Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals (CIs) for all-cause mortality, cardiovascular diseases, stroke and heart failure in participants with and without LVH at baseline. The mean follow-up was 2.1 years. RESULTS: LVH identified by CV-LVH or CP-LVH criteria was associated with a 1.6-1.9-fold risk of cardiovascular disease and stroke. The presence of CP-LVH was associated with an increased risk of heart failure (hazard ratio 2.38, 95% CI 1.16-4.86). In sex-specific analyses, CV-LVH (hazard ratio 1.94, 95% CI 1.06-3.55) and CP-LVH (hazard ratio 2.36, 95% CI 1.25-4.45) were associated with an increased risk of stroke in women and of heart failure in men, CV-LVH (hazard ratio 6.47, 95% CI 1.41-29.79) and CP-LVH (10.63, 95% CI 3.58-31.57), respectively. There was no significant increase in the risk of any outcomes associated with Sokolow-Lyon-LVH. LVH identified by these three methods was not a significant predictor of all-cause mortality. CONCLUSION: Use of Cornell voltage and Cornell product criteria for LVH predicted the risk of cardiovascular disease and stroke. Only Cornell product was associated with an increased risk of heart failure. This was particularly the case in men. The identification of ECG LVH proved to be important in very elderly hypertensive people.

Prognostic Effect of the Nocturnal Blood Pressure Fall in Hypertensive Patients: The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) Meta-Analysis.

The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day ratio and for different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. ABC-H investigators provided multivariate adjusted hazard ratios (HRs), with and without adjustment for 24-hour SBP, for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Average 24-hour SBP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93. There were 1769 total CVEs, 916 coronary events, 698 strokes, 450 cardiovascular deaths, and 903 total deaths. After adjustment for 24-hour SBP, the systolic night-to-day ratio predicted all outcomes: from a 1-SD increase, summary HRs were 1.12 to 1.23. Reverse dipping also predicted all end points: HRs were 1.57 to 1.89. Reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Risks for extreme dippers were significantly influenced by antihypertensive treatment (P<0.001): untreated patients had increased risk of total CVEs (HR, 1.92), whereas treated patients had borderline lower risk (HR, 0.72) than normal dippers. For CVEs, heterogeneity was low for systolic night-to-day ratio and reverse/reduced dipping and moderate for extreme dippers. Quality of included studies was moderate to high, and publication bias was undetectable. In conclusion, in this largest meta-analysis of hypertensive patients, the nocturnal BP fall provided substantial prognostic information, independent of 24-hour SBP levels.

Effect of resistance training on resting blood pressure: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the influence of resistance training on resting blood pressure in healthy sedentary adults. METHODS: A comprehensive literature search with the MEDLINE computerized database was conducted and reference lists of published articles and reviews on the topic were checked. Inclusion criteria were as follows: the study involved a randomized, controlled trial; resistance training was the sole intervention; participants were sedentary normotensive and/or hypertensive adults with no other concomitant disease; the article was published in a peer-reviewed journal up to December 2003. We identified nine randomized controlled trials, involving 12 study groups and 341 participants. A standard protocol was used to extract information on sample size, participant characteristics, study design, training method and duration, and study outcomes. Pooled blood pressure estimates were obtained, weighted by either the number of participants in the training group or the inverse of the variance for blood pressure change. RESULTS: The weighted net changes of blood pressure, after adjustment for control observations, averaged -3.2 [95% confidence limits (CL) -7.1 to +0.7]/-3.5 (95% CL -6.1 to -0.9) mmHg when weighted for the number of trained participants, and -6.0 (95% CL -10.4 to -1.6)/ -4.7 (95% CL -8.1 to -1.4) mmHg, when weighted by the reciprocal of the variance for the blood pressure change. CONCLUSIONS: Our results suggest that moderate intensity resistance training is not contraindicated and could become part of the non-pharmacological intervention strategy to prevent and combat high blood pressure. However, additional studies are needed, especially in the hypertensive population.

Influence of the endothelial nitric oxide synthase gene on conventional and ambulatory blood pressure: sib-pair analysis and haplotype study.

BACKGROUND: Nitric oxide is involved in the regulation of vascular basal tone and blood pressure. Polymorphisms of NOS3, the gene that codes for endothelial nitric oxide synthase, have been associated with essential hypertension. OBJECTIVE: To look for linkage and association of three di-allelic polymorphisms (Glu298Asp, intron 4 VNTR and T-786C) and the intron 13 CA-repeat of NOS3 with blood pressure as a continuous trait. METHODS: Genotyping was performed in 110 dizygotic white twin pairs from Flanders, Belgium. The influence of NOS3 polymorphisms on conventional and ambulatory blood pressure was assessed by sib-pair analysis and haplotype association analysis. RESULTS: Genotype frequencies were similar to those previously reported in white populations. Sib-pair analysis did not show a significant influence of either polymorphism on blood pressure. Haplotype analysis disclosed a significant association between NOS3 haplotypes and daytime ambulatory diastolic (P = 0.02) and systolic (P < 0.0001) blood pressure, the latter remaining significant after multiple testing was taken into account (P = 0.032). The association between daytime ambulatory systolic blood pressure and NOS3 haplotypes was mainly attributable to four haplotypes accounting for 11.9% of all represented haplotypes. CONCLUSION: We show for the first time a highly significant association of ambulatory blood pressure with NOS3 haplotypes in well-characterized white individuals from Flanders. These results pave the way for studies looking for the influence of NOS3 on blood pressure in high-risk subsets such as diabetic or hypertensive patients. They indicate the importance of ambulatory blood pressure and haplotype analysis in revealing the moderate effect of polymorphisms on blood pressure.

Collagen production in cardiac fibroblasts during inhibition of aminopeptidase B.

OBJECTIVE: To determine whether the aminopeptidase B inhibitor, arphamenine A, could affect collagen production and expression in control and TGF-ss1-treated cardiac fibroblasts. DESIGN AND METHODS: Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency and incubated with and without 600 pmol/l TGF-ss1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with 100 mol/l arphamenine A for 1 day in this medium with added ascorbic acid, ss-aminopropionitrile and titriated proline. Soluble collagen was measured in the conditioned medium and non-soluble collagen in the cell layer. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine- or arginine-p-nitroanilide. Matrix metalloproteinase (MMP) and lysyl oxidase activity were assayed in the conditioned medium. A semi-quantitative reverse transcriptase- polymerase chain reaction was used to examine the expression of lysyl oxidase and collagen type I and III. RESULTS: Arphamenine A dose-dependently inhibited basal and TGF-ss1-stimulated aminopeptidase activity. Arphamenine A reduced soluble and non-soluble collagen production in control and TGF-ss1-treated cardiac fibroblasts, while it decreased collagen type I and III expression only in TGF-ss1-treated fibroblasts. Lysyl oxidase, MMP-1 and MMP-2 activity were inhibited by arphamenine A in the conditioned media of control and TGF-ss1-treated cardiac fibroblasts. CONCLUSIONS: Our data show that the specific aminopeptidase B inhibitor, arphamenine A, reduces collagen production in cardiac fibroblasts and that this reduction is accompanied by a pronounced inhibition of lysyl oxidase.

Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension.

OBJECTIVE: To examine the association of clinic and ambulatory heart rate with total, cardiovascular, and noncardiovascular death in a cohort of elderly subjects with isolated systolic hypertension from the Systolic Hypertension in Europe Trial. METHODS: A total of 4682 patients participated, whose untreated blood pressure on conventional measurement at baseline was 160 to 219 mm Hg systolic and lower than 95 mm Hg diastolic. Clinic heart rate was the mean of 6 readings during 3 visits. Ambulatory heart rate was recorded with a portable intermittent technique in 807 subjects. RESULTS: Raised baseline clinic heart rate was positively associated with a worse prognosis for total, cardiovascular, and noncardiovascular mortality among the 2293 men and women taking placebo. Subjects with heart rates higher than 79 beats/min (bpm) (top quintile) had a 1.89 times greater risk of mortality than subjects with heart rate lower than or equal to 79 bpm (95% confidence interval, 1.33-2.68 bpm). In a Cox regression analysis, predictors of time to death were heart rate (P<.001), age (P<.001), serum creatinine level (P =.001), presence of diabetes (P =.002), previous cardiovascular disease (P =.01), triglyceride readings (P =.02), smoking (P =.04), and elevated systolic blood pressure (P =.05), while total cholesterol level was found to be nonsignificant in the model. In the ambulatory monitoring subgroup, clinic and ambulatory heart rates predicted noncardiovascular but not cardiovascular mortality. However, in a Cox regression analysis in which clinic and ambulatory heart rates were included, a significant association with noncardiovascular mortality was found only for clinic heart rate (P =.004). In the active treatment group, the weak predictive power of clinic heart rate for mortality disappeared after adjustment for confounders. CONCLUSIONS: In untreated older patients with isolated systolic hypertension, a clinic heart rate greater than 79 bpm was a significant predictor of all-cause, cardiovascular, and noncardiovascular mortality. Ambulatory heart rate did not add prognostic information to that provided by clinic heart rate.

Prognostic impact of sex-ambulatory blood pressure interactions in 10 cohorts of 17 312 patients diagnosed with hypertension: systematic review and meta-analysis.

BACKGROUND: Whether ambulatory blood pressure (BP) among hypertensive patients better predicts cardiovascular events (CVEs) in women relative to men is unclear. METHODS: We searched PUBMED and OVID databases. Cohorts were required to have hypertension, 1+ years of follow-up, with stroke and coronary artery disease as outcomes. Lead investigators for these cohorts provided ad hoc analyses. Random-effect meta-analyses gave hazard ratios for CVEs from a 1 standard deviation (SD) mmHg increase and a 10 mmHg increase in SBP. Subgroup and meta-regression analyses quantified the relative increase in risk in women versus men. RESULTS: Patients were from Europe, Brazil, and Japan (10 cohorts, n = 17 312, CVEs = 1892). One cohort lacked sex-specific hazard ratios from 24 h and clinic SBP. Compared with men, women tended to have greater SDs and coefficients of variation of SBP. Subgroup analyses showed higher hazard ratios in women than in men from increases in ambulatory but not clinic SBPs. For women relative to men, a 1 SD increase in night-time, daytime, 24 h, and clinic SBP gave hazard ratios (95% confidence limits) of 1.17 (1.06-1.30), 1.24 (1.10-1.39), 1.21 (1.08-1.36), and 0.94 (0.84-1.05), respectively, whereas a 10 mmHg increase in SBP, gave hazard ratios of 1.06 (0.99-1.14), 1.13 (1.03-1.23), 1.10 (1.01-1.21), and 0.96 (0.89-1.03), respectively. CONCLUSION: In patients with hypertension, increases in ambulatory, but not clinic, SBP predict higher risks for CVEs in women than in men. Although women tended to have greater variability in SBP, this did not entirely explain the sex-ambulatory BP interactions.

Collagen production in cardiac fibroblasts during inhibition of angiotensin-converting enzyme and aminopeptidases.

OBJECTIVE: To determine whether lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, and bestatin, an aminopeptidase inhibitor with broad specificity, could affect collagen production in control and transforming growth factor (TGF)-beta1-treated cardiac fibroblasts. DESIGN AND METHODS: Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency, incubated with or without 600 pmol/l TGF-beta1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with the test products (lisinopril or bestatin) for 1 day in this medium with added ascorbic acid, beta-aminoproprionitrile and tritiated proline. Soluble collagen was measured in the conditioned medium and non-soluble collagen in the cell layer. ACE activity was measured fluorimetrically with hippuryl-histidyl-leucine as substrate, and DNA with the bisbenzimide dye, Hoechst 33,258. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine-p-nitroanilide. RESULTS: Lisinopril dose-dependently reduced ACE activity in control and TGF-beta1-treated cardiac fibroblasts. Bestatin inhibited the basal and TGF-beta1-stimulated aminopeptidase activity in a concentration-dependent manner. Lisinopril (10 micromol/l) decreased (P < 0.05) the production of soluble and non-soluble collagen in control cardiac fibroblasts. TGF-beta1 (600 pmol/l) increased (P < 0.05) the production of soluble and non-soluble collagen, and this effect was decreased (P < 0.05) by lisinopril. Bestatin (100 micromol/l) reduced (P < 0.01) the production of soluble collagen in control and TGF-beta1-treated cardiac fibroblasts, but did not affect the production of non-soluble collagen in these cells. CONCLUSIONS: Our data suggest that ACE and aminopeptidases are involved in the basal and TGF-beta1-stimulated production of collagen in adult rat cardiac fibroblasts in culture.

Survey on treatment of hypertension and implementation of World Health Organization/International Society of Hypertension risk stratification in primary care in Belgium.

OBJECTIVE: To gain insight into the prevalence, treatment and control of hypertension and into the implementation of the 1999 World Health Organization/International Society of Hypertension guidelines for the management of hypertension in general practice in Belgium. DESIGN: A prospective cross-sectional survey. SETTING: Primary care. METHODS: Participating physicians enrolled the first 15 men, at least 55 years old, who visited the surgery, measured their blood pressure with a validated automatic device and recorded data on age, medical history, drug utilization, cardiovascular risk factors and target organ damage. Patients were considered to have hypertension when systolic blood pressure was >or= 140 mmHg, diastolic blood pressure was >or= 90 mmHg or when they were under antihypertensive therapy. RESULTS: Among 3761 evaluable patients, 74% were considered to be hypertensive, 80% of whom were treated with antihypertensive drugs. Blood pressure was under control in 38% of the treated patients and in 31% of all hypertensives. Among the 1316 hypertensive patients in whom risk stratification was possible, 47, 56 and 86% of the patients in, respectively, the medium, high and very high risk groups were treated with antihypertensive drugs. Among the treated patients, 46, 37 and 31%, respectively, had reached goal pressure. Within each risk category, patients were treated more frequently when baseline blood pressure was higher. Logistic regression analysis revealed that hypertension grade and level of risk contributed independently to the odds of being treated. CONCLUSIONS: The results indicate that a large number of older hypertensive men are treated with antihypertensive drugs in primary care, but that the goal blood pressure is not reached in a substantial number of patients due to undertreatment. Furthermore, whereas patients at higher risk are treated more frequently than patients at lower risk, blood pressure itself remains an important factor for the initiation of antihypertensive drug therapy within each risk category.

Influence of chorionicity on the heritability estimates of blood pressure: a study in twins.

BACKGROUND: A basic assumption of the twin design is that environmental influences including prenatal experiences are equal across twin types. However, the intra-uterine environment may differ according to the chorionicity of the monozygotic twins, which may have biased previous heritability estimates of blood pressure. OBJECTIVE: The aim of the present study was to assess whether the heritability of blood pressure, derived from measurements in monozygotic and dizygotic twins, differs according to the chorionicity of the monozygotic twins. METHODS: Conventional and 24-h ambulatory blood pressures were measured in 125 dizygotic twin pairs and in 97 dichorionic and 128 monochorionic monozygotic twin pairs at the age of 18-34 years. The twin sample was drawn from the East Flanders Prospective Twin Survey, in which perinatal data were collected at birth. Intra-pair correlation coefficients were calculated and compared between both types of monozygotic twin pairs. Heritability was estimated from model-fitting and path analysis, based on the dizygotic twins and, respectively, all monozygotic twins and the two subtypes. RESULTS: Intra-pair correlation coefficients for the various blood pressures, after adjustment for body mass index, ranged from 0.45 to 0.71 in the monozygotic twin pairs and did not differ significantly according to chorionicity. Heritability estimates of blood pressure were between 52 and 64%, and were similar when calculated from dizygotic twins and, respectively, dichorionic and monochorionic monozygotic twins. CONCLUSIONS: Heritability estimates of conventional and ambulatory blood pressure do not differ significantly according to the chorionicity of the monozygotic twins.

Host and environmental determinants of heart rate and heart rate variability in four European populations.

OBJECTIVE: In a population-based sample of nuclear families recruited in the framework of the European Project on Genes in Hypertension (EPOGH), we investigated the association between heart rate (HR) and its variability (HRV), and gender, age, posture, breathing frequency, body mass index, systolic blood pressure, family history of hypertension and various lifestyle factors, such as smoking, alcohol and coffee consumption and physical activity. METHODS: RR interval and respiration were registered in the supine and standing positions (15 min each) in 1208 subjects in Bucharest (Romania, n= 267), Cracow (Poland, n= 323), Mirano (Italy, n= 323) and Novosibirsk (Russian Federation, n= 295). After exclusion of 199 participants on antihypertensive treatment and/or patients with diabetes mellitus (n= 40) or myocardial infarction (n= 4), 993 subjects were eligible for analysis. We evaluated 858 participants with high-quality recordings. Using fast Fourier transform, we decomposed HRV into low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: 0.15-0.40 Hz) components, which were expressed in normalized units. RESULTS: Mean values were 35.3 years for age, 24.3 kg/m for body mass index (BMI) and 121.0/77.2 mmHg for blood pressure. The group included 462 (53.8%) women. Across four centres, HR and HRV were similarly and independently associated with gender, age and postural position (P <0.001). In the supine position, HR was higher in women than men (67.2 versus 63.7 bpm). Men had higher normalized LF power than women (48.8 versus 41.5), but lower HF power (40.6 versus 47.4). The normalized HF power decreased with age (r = -0.43), whereas LF power increased (r = 0.32). On standing, HR increased (83.3 versus 65.6 bpm), normalized HF power declined (19.2 versus 44.3) and LF power increased (67.4 versus 44.9). The independent effects of respiration frequency, systolic blood pressure, family history of hypertension, body mass index and lifestyle factors on HRV differed between populations, and explained no more than 8% of the total variance. CONCLUSIONS: Across four European populations, gender, age and posture were consistent and independent correlates of HR and HRV. Lifestyle seems to have small but varying influences on HR and/or HRV, probably depending on the environmental and cultural background of the population under study.