Association of depression with mortality in an elderly treated hypertensive population.

ABSTRACTBackground:Both elevated blood pressure and/or depression increase the risk of cardiovascular disease and mortality. This study in treated elderly hypertensive patients explored the incidence of depression, its association (pre-existing and incident) with mortality and predictors of incident depression. METHODS: Data from 6,083 hypertensive patients aged ≥65 years enrolled in the Second Australian National Blood Pressure study were used. Participants were followed for a median of 10.8 years (including 4.1 years in-trial) and classified into: "no depression," "pre-existing" and "incident" depression groups based on either being "diagnosed with depressive disorders" and/or "treated with an anti-depressant drug" at baseline or during in-trial period. Further, we redefined "depression" restricted to presence of both conditions for sensitivity analyses. For the current study, end-points were all-cause and any cardiovascular mortality. RESULTS: 313 (5%) participants had pre-existing depression and a further 916 (15%) participants developed depression during the trial period (incidence 4% per annum). Increased (hazard-ratio, 95% confidence-interval) all-cause mortality was observed among those with either pre-existing (1.23, 1.01-1.50; p = 0.03) or incident (1.26, 1.12-1.41; p < 0.001) depression compared to those without. For cardiovascular mortality, a 24% increased risk (1.24, 1.05-1.47; p = 0.01) was observed among those with incident depression. The sensitivity analyses, using the restricted depression definition showed similar associations. Incident depression was associated with being female, aged ≥75 years, being an active smoker at study entry, and developing new diabetes during the study period. CONCLUSIONS: This elderly cohort had a high incidence of depression irrespective of their randomised antihypertensive regimen. Both pre-existing and incident depression were associated with increased mortality.

Leasing a medical curriculum: What's it worth?

Introduction: The early part of this century saw an unprecedented growth in number and size of Australian medical schools. There was some partnering of the new schools with existing programs. Griffith, Deakin and Curtin Universities leased an established curriculum from Flinders University. Nature and rationale for curriculum leasing: The new schools had short startup times and leasing a curriculum enabled them to appoint key staff, develop facilities and meet accreditation requirements in a timely way. However, the lease arrangements were costly and the curriculum was largely determined before the Dean and key staff appointments. Outcomes of leasing: There was differential adoption of the leased curriculum. The first two years of the courses at Flinders were transferred with little change. The final two years of predominantly clinical studies were developed differently. This is explained through Michael Fullan's work on context in educational change. The context of the clinical years of the courses involved negotiations with local health services and other schools using those health services. The advantage of the leasing arrangements was that the new schools could proceed through early development and accreditation, while having time and opportunity to negotiate a clinical curriculum that engaged local health services and fulfilled the new schools' missions.

Glomerular hyperfiltration is a predictor of adverse cardiovascular outcomes.

The association between glomerular hyperfiltration and cardiovascular events is not well known. To investigate whether glomerular hyperfiltration is independently associated with risk of adverse outcome we analyzed 8794 participants, average age 52 years enrolled in 8 prospective studies. Of these, 89% had hypertension. Using the 5th and 95th percentiles of the age- and sex-specific quintiles of CKD-EPI-calculated estimated glomerular filtration rate (eGFR), we identified three participant groups with low, high and normal eGFR. The ambulatory pulse pressure interval was wider and nighttime blood pressure fall was smaller in both the low and high than in the normal eGFR participants. During a mean follow-up of 6.2 years, there were 722 cardiovascular events. Crude event rates were significantly higher for both high (1.8 per 100-person-year) and low eGFR groups (2.1 per 100 person-year) as compared with group with normal eGFR (1.2 per 100 person-year). In multivariable Cox models including age, sex, average 24-hour blood pressure, smoking, diabetes, and cholesterol, both high eGFR (hazard ratio 1.5 (95% confidence interval 1.2-2.1) and low eGFR (2.0 [1.5-2.6]) participants had a significantly higher risk of cardiovascular events as compared to those with normal eGFR. Addition of body mass index to the multivariable survival model did not change the magnitude of hazard estimates. Thus, glomerular hyperfiltration is a strong and independent predictor of cardiovascular events in a large multiethnic population of predominantly hypertensive individuals. Our findings support a U-shaped relationship between eGFR and adverse outcome.

Association of Extreme Nocturnal Dipping With Cardiovascular Events Strongly Depends on Age.

Whether extreme dipping is associated with cardiovascular events (CVE) is unclear. The present study was conducted to test the hypothesis that the prognostic role of extreme dipping varies as a function of age. The analysis was performed in 10 868 participants (53% men) aged 53±15 (mean±SD) years enrolled in 8 prospective studies. Using the ambulatory systolic blood pressure nocturnal decline, we identified 4 groups: dippers (>10%-20%), nondippers (>0%-10%), reverse dippers (≤0%), and extreme dippers (>20%). The association between dipping category and CVE was estimated as a function of age using Cox models adjusted for sex, average 24-hour systolic blood pressure, and traditional risk factors. During a median follow-up of 5.7 years, there were a total of 829 CVE (168 fatal). For extreme dippers, no increase in risk of CVE was observed among the participants <70 years (hazard ratio, 0.99 [95% CI, 0.73-1.34]; P=0.93) compared with dippers. In contrast, among the participants ≥70 years, there was a significant increase in risk (hazard ratio, 1.88 [95% CI, 1.14-3.11]; P=0.013). Among the octogenarians, the hazard ratio (95% CI) for CVE were 2.34 (1.12-4.93) for nondippers (P=0.024), 3.91 (1.75-8.73) for reverse dippers (P=0.001), and 4.12 (1.64-10.37) for extreme dippers (P=0.003) compared with dippers. These data show that extreme dipping is not associated with poorer outcome in people younger than 70 years. A U-shaped relationship between nocturnal blood pressure dipping and adverse outcome is present in subjects older than 70 years. In the octogenarian extreme dippers, the risk of CVEs was 4× higher than in the dippers and similar to that in the reverse dippers.

Change in Blood Pressure Variability Among Treated Elderly Hypertensive Patients and Its Association With Mortality.

Background Information is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long-term mortality in an elderly hypertensive population. Methods and Results We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24-hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow-up). Weighted day-night systolic BPV was calculated for both baseline and follow-up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV, stable: high BPV, decline: high to low, and increase: low to high. We observed an annual decline (mean±SD: -0.37±1.95; 95% CI, -0.54 to -0.19; P<0.001) in weighted day-night systolic BPV between baseline and follow-up. Having constant stable: high BPV was associated with an increase in all-cause mortality (hazard ratio: 3.03; 95% CI, 1.67-5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62-8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow-up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Conclusions Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow-up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long-term mortality.

Short- and long-term association of lipid-lowering drug treatment and cardiovascular disease by estimated absolute risk in the Second Australian National Blood Pressure study.

BACKGROUND: There is currently insufficient evidence to support the use of lipid-lowering drug treatment (LLT) for primary prevention of cardiovascular disease (CVD) in the elderly. OBJECTIVES: We examined the relationship of early initiation of LLT with short- and long-term all-cause and CVD mortality in persons older than 65 years in this post hoc study from the Second Australian National Blood Pressure study (ANBP2). METHODS: This was an in- and post-trial observational study. About 4257 hypertensive participants aged 65 to 84 years within Australian family practices were randomized to an angiotensin-converting enzyme inhibitor or a diuretic treatment group. After excluding participants with a prior history of CVD, the cohort was stratified into "LLT" and "no LLT" subgroups based on LLT status at randomization. RESULTS: At randomization, the participants had a mean age of 72 years, average blood pressure of 168/91 mm Hg and estimated 5-year CVD risk of 18.7 ± 8.3%. In the overall study population, the association of LLT with long-term (11-years) all-cause and non-CVD mortality was significant (hazard ratio [HR] 0.78 [95% confidence interval {CI} 0.66-0.92, P = .003] and HR 0.70 [95% CI 0.54-0.90, P = .006], respectively). Magnitudes of the association of LLT with long-term mortality and the association with short-term mortality were similar; however, no statistically significant association with short-term mortality was observed. In the subgroup analysis by baseline 5-year CVD risk, LLT participants in the highest risk tertile had a substantially lower relative risk for short-term all-cause mortality (HR 0.31, 95% CI 0.13-0.71, P for interaction .02) compared to those with lower estimated CVD risk. All analyses were adjusted for baseline and in-trial characteristics. CONCLUSION: Our study showed a strong association between LLT and reduced long-term all-cause mortality. Thus, our findings support recommendations of the use of LLT in patients over 65 years, particularly those with high CVD risk who were more likely to obtain additional benefits in the short term. The findings also suggested that mortality benefits of LLT for the elderly may take longer to become evident.

Added predictive value of high uric acid for cardiovascular events in the Ambulatory Blood Pressure International Study.

The prognostic value of uric acid (UA) for cardiovascular events (CVE) is still debated. Our purpose was to investigate the association between UA and CVE in 5243 participants of the ABP-International study with the main aim of identifying optimal sex-specific cut-points. In multivariable Cox analyses, the relationship between CVE and UA as a continuous variable was modeled by including both linear and nonlinear terms. Survival models were also estimated with UA as a categorical variable. Optimal UA cut-points were determined using an outcome-oriented approach. During a median follow-up of 5.9 years, there were 423 CVE (93 fatal). In age- and sex-adjusted Cox models, UA as a continuous variable was a significant predictor of CVE in all individuals and in men and women considered separately. The relationship between UA and CVE was linear (P-value for nonlinearity 0.54 and 0.80 for men and women, respectively). For each 1 mg/dL increase in UA, the relative hazard increase was 16% in men and 19% in women. In fully adjusted models, UA remained a significant predictor of CVE in the whole study cohort. The optimal cut-point best separating patients at low and high risk of CVE was 6.3 mg/dL for men and 4.4 mg/dL for women. Subjects with high UA had a 38% greater risk of CVE. In a sex-specific analysis, the association remained significant only in men (hazard ratio, 1.47; P < 0.01). In conclusion, high UA is an independent predictor for subsequent CVE and significantly improves risk discrimination and reclassification over the baseline multivariable model.

Visit-to-visit (long-term) and ambulatory (short-term) blood pressure variability to predict mortality in an elderly hypertensive population.

OBJECTIVES: To explore the association of different types of blood pressure (BP) variability measures estimated from either short-term ambulatory reading-to-reading or long-term clinic visit-to-visit BP records with long-term survival in an elderly treated hypertensive population. METHODS: A subset of patients (n = 508) aged at least 65-years was studied from the Second Australian National Blood Pressure study. We estimated SBP and DBP BP variability as the SD of ambulatory (24-h, daytime, night-time) and clinic visit-to-visit BP directly from all corresponding on-treatment within-individual BP records. Ambulatory 'weighted day-night' variability was calculated as a weighted mean of daytime and night-time SD. Cox-proportional hazard models adjusted for baseline risk factors (Model 1) and corresponding on-treatment BP (Model 2) or average night-time SBP (best predictive BP measure for outcome) (Model 3) were used to determine the relationship between long-term outcome and BP variability. RESULTS: Over a median of 10.6 years, 101 patients died from any cause, of which 51 deaths were cardiovascular. We observed increase in 'daytime' and 'weighted day-night' SBP/DBP variability was significantly associated with increased all-cause mortality in all models. For cardiovascular mortality, only 'weighted day-night' SBP variability significantly predicted risk in all models (Model 3 hazard ratio: 1.09, 95% confidence interval: 1.00-1.19, P = 0.04). Long-term BP variability was not associated with any outcome. On direct comparison, both 'daytime' and 'weighted day-night' BP variability measures provided similar prognostic information. CONCLUSION: Short-term 'daytime' and 'weighted day-night' SBP variability from ambulatory BP recordings was a better predictor of mortality in elderly treated hypertensive patients than long-term BP variability from visit-to-visit BP recordings.

Night-time ambulatory blood pressure is the best pretreatment blood pressure predictor of 11-year mortality in treated older hypertensives.

BACKGROUND: Numerous studies have shown a stronger relationship between ambulatory blood pressure (ABP), particularly night ABP, and cardiovascular events/mortality than for office blood pressure (OBP). A previous clinical trial (Syst-Eur) showed that pretreatment ABP was only a better predictor of outcome than OBP in placebo-treated participants. The current study in treated elderly hypertensives from the Second Australian National Blood Pressure study (ANBP2) examined whether pretreatment ABP was a better predictor of mortality than OBP over long-term (∼11 years) follow-up. PARTICIPANTS AND METHODS: ANBP2 was a comparative outcome trial in 6083 off-treatment or previously untreated elderly hypertensives. In the ABP substudy, at study entry, participants had ABP and nurse-performed OBP measurements. Cox proportional hazards analysis assessed the relationships between both OBP and ABP at study entry and 11-year all-cause and cardiovascular mortality, with results pooled from both active treatment phases. RESULTS: In 702 participants, over a median of 10.8 years, including 6.7 years after the trial, 167 died (82 cardiovascular). Pretreatment 'night' systolic ABP and pulse pressure were the best predictors of '11-year' cardiovascular mortality (hazard ratios: 1.26; 95% confidence intervals: 1.10-1.45, P=0.001 and 1.18; 1.06-1.31, P=0.003, respectively) and all-cause mortality (hazard ratios: 1.15; 95% confidence intervals:1.05-1.28, P=0.005 and 1.09; 1.10-1.31, P=0.03, respectively). OBP was not a significant predictor of mortality. CONCLUSION: In actively treated elderly hypertensives participating in ANBP2, all-cause or cardiovascular deaths were significantly related to pretreatment ABP, particularly to night-time systolic ABP and pulse pressure, but not to OBP.

Relation of Alcohol Consumption to Risk of Heart Failure in Patients Aged 65 to 84 Years With Hypertension.

Although a high level of alcohol consumption is associated with cardiomyopathy, the benefit or risk of moderate alcohol consumption on incident heart failure (HF) is unknown. This study examined the association between alcohol consumption and risk for HF in older adults with hypertension. The study analyzed data from a cohort of 6,083 participants aged 65 to 84 years at baseline (1995 to 2001) followed for a median of 10.8 years during and after the Second Australian National Blood Pressure Study. Frequency and amount of alcohol consumption were self-reported at baseline and during the clinical trial. The percentages of current drinkers, former drinkers, and never-drinkers at baseline were 4,400 (72%), 394 (6%), and 1,289 (21%), respectively. Incident HF was diagnosed in 183 men and 136 women. After adjustment for multiple confounders, alcohol consumption was not significantly associated with HF. Compared with never-drinkers, the adjusted hazard ratios (95% confidence interval) for those who consume 1 to 7, 8 to 14, and >14 drinks/week at baseline were 0.87 (0.59 to 1.30), 0.96 (0.57 to 1.60), and 0.71 (0.25 to 2.02), respectively in women, and 0.81 (0.47 to 1.38), 0.77 (0.43 to 1.38), and 1.04 (0.59 to 1.84), respectively in men. The findings of lack of an association between alcohol consumption and risk of HF persisted in the analyses comparing the risk of HF across each level of drinking at baseline or at follow-up with never-drinkers. In the present study, there was no evidence for benefit or risk of alcohol consumption, reported at baseline or at follow-up, in relation to incident HF in both men and women.

A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly.

BACKGROUND: Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents. METHODS: We conducted a prospective, randomized, open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practices. Subjects were followed for a median of 4.1 years, and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models. RESULTS: At base line, the treatment groups were well matched in terms of age, sex, and blood pressure. By the end of the study, blood pressure had decreased to a similar extent in both groups (a decrease of 26/12 mm Hg). There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group (56.1 per 1000 patient-years) and 736 cardiovascular events or deaths from any cause in the diuretic group (59.8 per 1000 patient-years; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05). Among male subjects, the hazard ratio was 0.83 (95 percent confidence interval, 0.71 to 0.97; P=0.02); among female subjects, the hazard ratio was 1.00 (95 percent confidence interval, 0.83 to 1.21; P=0.98); the P value for the interaction between sex and treatment-group assignment was 0.15. The rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment, whereas a similar number of strokes occurred in each group (although there were more fatal strokes in the ACE-inhibitor group). CONCLUSIONS: Initiation of antihypertensive treatment involving ACE inhibitors in older subjects, particularly men, appears to lead to better outcomes than treatment with diuretic agents, despite similar reductions of blood pressure.

Prediction of strokes versus cardiac events by ambulatory monitoring of blood pressure: results from an international database.

We performed this study to elucidate the role of nighttime versus daytime ambulatory blood pressure in predicting stroke and cardiac events. The International Collaborative Study of the Prognostic Utility of ABPM, which includes prospective cohort studies of ambulatory blood pressure monitoring (ABPM) from seven sites, was analyzed in this study. The incidence of stroke and cardiac events were evaluated for an average of 5.8 years. A cox proportional hazards model of adjusting for site, age, sex, BMI, total cholesterol, smoking, and history of antihypertensive medications was used for the analysis. Dipping was defined as the percentage decline in nighttime systolic blood pressure (SBP) relative to daytime SBP. Three hundred and eleven cardiac events and 318 strokes were seen during the follow up periods. Awake and sleep SBP were both significantly associated with both cardiac and stroke events. When the awake and sleep SBP were entered together in the model, awake SBP was more strongly associated with cardiac events than sleep SBP (chi2=12.4, d.f.=1, P=0.0004); conversely, sleep SBP (chi2=13.5, d.f.=1, P<0.0002) was more predictive for stroke events than awake SBP, although awake SBP also remained a significant predictor (chi2=7.03, d.f.=1, P=0.008). The amount of dipping was a significant inverse predictor of stroke [hazards ratio (HR) 0.81 per 10% increase in dipping, confidence interval (CI) 0.70-0.94, chi2=7.70, d.f.=1, P=0.006] but not of cardiac events. It should not be assumed that one summary measure of ambulatory blood pressure would be the best predictor of different clinical outcomes.

Long-term survival following the development of heart failure in an elderly hypertensive population.

BACKGROUND: Available data on the prognosis of heart failure (HF) patients are predominantly limited to patients diagnosed at time of hospitalization. AIMS: To describe the long-term survival of incident HF patients and identify clinical characteristics associated with mortality. METHODS: The Second Australian National Blood Pressure Study (ANBP2) randomized 6083 hypertensive subjects aged 65-84 years to angiotensin-converting enzyme (ACE) inhibitor or thiazide diuretic-based therapy and followed them for a median of 4.1 years. One hundred forty-five participants who developed HF and 5938 who remained free from HF during the trial period were followed for a median of 6.7 years during a posttrial follow-up. RESULTS: Three quarters, 110 (76%) of HF patients had died at the end of the follow-up. The five- and ten-year survival rates following HF diagnosis during the trial period were 37% and 15%, respectively, in men, compared with 60% and 33%, respectively, in women. In non-heart failure participants, the five- and ten-year survival rates, following enrollment into the study, were 92% and 76%, respectively. Mortality following HF diagnosis increased with advancing age (HR = 1.09, 95% CI: 1.04-1.33). In addition, male gender and preexisting diabetes were predictive of mortality, while ACE inhibitor-based therapy for the initial trial was associated with 39% decrease (HR = 0.61, 95% CI: 0.41-0.91) in mortality compared with a thiazide diuretic-based regimen. CONCLUSIONS: Long-term survival in elderly HF patients is poor, especially in men. Mortality in HF patients increased progressively with advancing age, while allocation to the ACE inhibitor-based regimen for the initial trial significantly improved HF outcome.

Pet ownership and survival in the elderly hypertensive population.

OBJECTIVES: To assess the association of pet ownership and all-cause and cardiovascular mortality over a long-term follow-up among elderly treated hypertensive participants. METHODS: Pet-ownership data from a subcohort of the Second Australian National Blood Pressure study were used. Participants were aged 65-84 years at enrolment (1995-1997) and responded to a pet-ownership questionnaire during year 2000. Participants' survival information was determined over a median of 10.9 years that includes Second Australian National Blood Pressure in-trial period (median 4.2 years) together with posttrial follow-up period (median 6.9 years). For the current study, end points were any fatal cardiovascular event and all-cause fatal events. RESULTS: Of those who responded to a pet-ownership questionnaire (4039/6018 - 67%), 86% (3490/4039) owned at least one pet at any-time during their life (current or previous pet owner), with 36% (1456/4039) owning at least one pet at the time of the survey. During the follow-up period, 958 participants died including 499 deaths of cardiovascular origin. Using a Cox proportional hazard regression model adjusting for possible confounders, there was a 22 and 26% reduction in cardiovascular mortality observed among previous and current pet owners, respectively, compared with those who had never owned one. A similar nonsignificant trend was observed for all-cause mortality once adjusted for potential confounders. CONCLUSION: Pet ownership was associated with an improved cardiovascular disease survival in a treated elderly hypertensive population.

Masked tachycardia. A predictor of adverse outcome in hypertension.

OBJECTIVE: The relative role of office heart rate (HR) and ambulatory HR for predicting major adverse cardiovascular events (MACEs) and mortality is not well known. Aim of this study was to investigate the association of white-coat tachycardia and masked tachycardia with MACE and mortality in hypertensive patients. METHODS: We performed 24-h ambulatory blood pressure and HR monitoring in 7602 hypertensive patients (4165 men) aged 52 ±â€Š16 years enrolled in six prospective studies in Italy, Japan, and Australia. Participants were divided into four groups: normal office and normal night-time HRs (N = 5238), white-coat tachycardia (N = 998), masked tachycardia (N = 796), and sustained tachycardia (N = 570). Median follow-up was 5.0 years. RESULTS: In age-and-sex-adjusted Cox model, using the normal HRs group as a reference, white-coat tachycardia was not a significant predictor of excess MACEs or all-cause death. In contrast, both masked tachycardia [hazard ratio, 95% confidence interval (CI); 1.40, 1.11-1.77] and sustained tachycardia (1.86, 1.44-2.40) were associated with risk of excess MACE. In addition, masked tachycardia (hazard ratio, 95% CI; 1.62, 1.14-2.29) but not sustained tachycardia (1.35, 0.83-2.19) was a significant predictor of excess mortality. These relationships held true in multivariable parsimonious Cox models including major risk factors. In these models, masked tachycardia remained an independent predictor of excess MACE (hazard ratio, 95% CI; 1.34, 1.06-1.71) and all-cause mortality (1.68, 1.18-2.41). CONCLUSION: The current study confirms that measurement of HR adds to the risk stratification for MACE and mortality and shows that an elevated night-time HR confers an increased mortality risk to hypertensive patients who have normal office HR.

Prediction of 10-year Risk of Incident Heart Failure in Elderly Hypertensive Population: The ANBP2 Study.

BACKGROUND: Multivariable risk prediction models consisting of routinely collected measurements can facilitate early detection and slowing of disease progression through pharmacological and nonpharmacological risk factor modifications. This study aims to develop a multivariable risk prediction model for predicting 10-year risk of incident heart failure diagnosis in elderly hypertensive population. METHODS: The derivation cohort included 6083 participants aged 65 to 84 years at baseline (1995-2001) followed for a median of 10.8 years during and following the Second Australian National Blood Pressure Study (ANBP2). Cox proportional hazards models were used to develop the risk prediction models. Variables were selected using bootstrap resampling method, and Akaike and Bayesian Information Criterion and C-statistics were used to select the parsimonious model. The final model was internally validated using a bootstrapping, and its discrimination and calibration were assessed. RESULTS: Incident heart failure was diagnosed in 319 (5.2%) participants. The final multivariable model included age, male sex, obesity (body mass index > 30kg/m2), pre-existing cardiovascular disease, average visit-to-visit systolic blood pressure variation, current or past smoking. The model has C-statistics of 0.719 (95% CI: 0.705-0.748) in the derivation cohort, and 0.716 (95% CI: 0.701-0.731) after internal validation (optimism corrected). The goodness-of-fit test showed the model has good overall calibration (χ 2 = 1.78, P = 0.94). CONCLUSION: The risk equation, consisting of variables readily accessible in primary and community care settings, allows reliable prediction of 10-year incident heart failure in elderly hypertensive population. Its application for the prediction of heart failure needs to be studied in the community setting to determine its utility for improving patient management and disease prevention.

Predictive Performance of Echocardiographic Parameters for Cardiovascular Events Among Elderly Treated Hypertensive Patients.

BACKGROUND: Hypertension leads to cardiac structural and functional changes, commonly assessed by echocardiography. In this study, we assessed the predictive performance of different echocardiographic parameters including left ventricular hypertrophy (LVH) on future cardiovascular outcomes in elderly hypertensive patients without heart failure. METHODS: Data from LVH substudy of the Second Australian National Blood Pressure trial were used. Echocardiograms were performed at entry into the study. Cardiovascular outcomes were identified over short term (median 4.2 years) and long term (median 10.9 years). LVH was defined using threshold values of LV mass (LVM) indexed to either body surface area (BSA) or height(2.7): >115/95g/m(2) (LVH-BSA(115/95)) or ≥49/45g/m(2.7) (LVH-ht(49/45)) in males/females, respectively, and ≥125g/m(2) (LVH-BSA(125)) or ≥51g/m(2.7) (LVH-ht(51)) for both sexes. RESULTS: In the 666 participants aged ≥65 years in this analysis, LVH prevalence at baseline was 33%-70% depending on definition; and after adjusting for potential risk factors, only LVH-BSA(115/95) predicted both short- and long-term cardiovascular outcomes. Participants having LVH-BSA(115/95) (69%) at baseline had twice the risk of having any first cardiovascular event over the short term (hazard ratio, 95% confidence interval: 2.00, 1.12-3.57, P = 0.02) and any fatal cardiovascular events (2.11, 1.21-3.68, P = 0.01) over the longer term. Among other echocardiographic parameters, LVM and LVM indexed to either BSA or height(2.7) predicted cardiovascular events over both short and longer term. CONCLUSIONS: In elderly treated hypertensive patients without heart failure, determining LVH by echocardiography is highly dependent on the methodology adopted. LVH-BSA(115/95) is a reliable predictor of future cardiovascular outcomes in the elderly.

Prognostic Value of Ambulatory Blood Pressure in the Obese: The Ambulatory Blood Pressure-International Study.

The purpose of this study was to compare the predictive value of ambulatory blood pressure (BP) vs office BP for cardiovascular events during a 5.8-year follow-up period in the obese and nonobese participants of the Ambulatory Blood Pressure-International Study (n=10,817). Both ambulatory BP and office BP considered separately were predictive of cardiovascular events. However, in Cox models including both pressures, only ambulatory BP was associated with outcome. Among obese patients, the hazard ratios for a 10-mm Hg increase in 24-hour and office systolic BPs were 1.37 (95% confidence interval, 1.20-1.53) and 0.91 (95% confidence interval, 0.76-1.07), respectively. Among nonobese patients, the corresponding hazard ratios were 1.39 (95% confidence interval, 1.31-1.47) and 0.94 (95% confidence interval, 0.88-1.00) (P=not significant vs obese). Similar results were obtained for diastolic BP and for daytime and nighttime BPs. Ambulatory BP has similar predictive capacity in obese and nonobese patients, suggesting that ambulatory BP monitoring is a useful diagnostic tool for the assessment of obese individuals.

Predictors of failure to initiate randomized treatment in a large trial of antihypertensive drug therapy in the aged.

BACKGROUND: The identification of factors that contribute to noncompliance with trial drug initiation where virtually complete compliance might be expected, may help identify patients whose management is least likely to comply with clinical guidelines and study protocols. METHODS: Examination of cross-sectional and longitudinal data arising from the Second Australian National Blood Pressure Study. Prevalence rate ratios (RR) and 95% confidence intervals (CI) estimated from log-binomial models were used to assess associations between subject characteristics and whether the randomized drug was prescribed at trial randomization. The study population consisted of 6083 hypertensive Australians aged 65 to 84 years. RESULTS: After adjusting for each variable in a multivariate model the following were significant predictors of failure to prescribe RR (95% CI): not previously prescribed antihypertensive drugs 2.89 (2.52-3.32); lower systolic blood pressure (BP) 1.51 (1.59-1.43) or diastolic BP 1.18 (1.22-1.13); younger age 80 to 84 v 65 to 79 years 0.75 (0.59-0.95); total cholesterol >or=6.6 v

Ten-year legacy effects of baseline blood pressure 'treatment naivety' in the Second Australian National Blood Pressure study.

OBJECTIVES: Current blood pressure (BP) management guidelines recommend that treatment thresholds for BP be based on absolute cardiovascular disease (CVD) risk rather than on elevated BP levels alone. Clinicians are concerned that delayed pharmacotherapy in individuals with high BP, but low CVD risk, may increase long-term CVD events. To investigate this, we examined differences in CVD events within the Second Australian National BP study (ANBP2) for those previously on pharmacotherapy and those who were not, as well as fatal events in the 6-year post-trial period. METHODS: Population consisted of ANBP2 participants without a prior CVD event. Adjusted Cox-regression hazard models were used to assess the effects of prior BP pharmacotherapy use on cardiovascular endpoints within ANBP2. An extended 6-year follow-up analysis for cardiovascular and all-cause mortality was also conducted. RESULTS: We found a higher in-trial CVD and all-cause mortality rate and incidence of new-onset diabetes for those on previous treatment versus those who were treatment-naive. We investigated whether this was an effect of the in-trial protocol, but this did not explain the observed differences. No difference in CVD or all-cause mortality at 10 years was observed between 'treatment-naive' and 'previous treatment' groups. CONCLUSION: We found no long-term adverse mortality associated with treatment naivety of elevated BP in an elderly hypertensive cohort, but this finding is likely to be confounded as seen by the lower in-trial mortality in the 'treatment-naive' group. Legacy effects need to be explored in randomized trials of middle-aged populations where the clinical concern lies.