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.

Prediction of cardiovascular and all-cause mortality at 10 years in the hypertensive aged population.

BACKGROUND: We have previously developed a score for predicting cardiovascular events in the intermediate term in an elderly hypertensive population. In this study, we aimed to extend this work to predict 10-year cardiovascular and all-cause mortality in the hypertensive aged population. METHODS: Ten-year follow-up data of 5,378 hypertensive participants in the Second Australian National Blood Pressure study who were aged 65-84 years at baseline (1995-2001) and without prior cardiovascular events were analyzed. By using bootstrap resampling variable selection methods and comparing the Akaike and Bayesian information criterion and C-indices of the potential models, optimal and parsimonious multivariable Cox proportional hazards models were developed to predict 10-year cardiovascular and all-cause mortality. The models were validated using bootstrap validation method internally and using the Dubbo Study dataset externally. RESULTS: The final model for cardiovascular mortality included detrimental (age, smoking, diabetes, waist-hip ratio, and disadvantaged socioeconomic status) and protective factors (female sex, alcohol consumption, and physical activity). The final model for all-cause mortality also included detrimental (age, smoking, random blood glucose, and disadvantaged socioeconomic status) and protective factors (female sex, alcohol consumption, body mass index, and statin use). Blood pressure did not appear in either model in this patient group. The C-statistics for internal validation were 0.707 (cardiovascular mortality) and 0.678 (all-cause mortality), and for external validation were 0.729 (cardiovascular mortality) and 0.772 (all-cause mortality). CONCLUSIONS: These algorithms allow reliable estimation of 10-year risk of cardiovascular and all-cause mortality for hypertensive aged individuals.

Systolic blood pressure variability is an important predictor of cardiovascular outcomes in elderly hypertensive patients.

OBJECTIVES: In hypertensive persons aged 60 years or below, visit-to-visit SBP variability is directly associated with cardiovascular events, especially stroke. It is unclear whether such a relationship exists for older persons. We investigated whether there is a relationship between visit-to-visit SBP variability and cardiovascular events in an elderly population, and identified the factors associated with increased SBP variability. METHODS: Information from 49771 visits of 5880 patients aged at least 65 years being treated for hypertension in the Second Australian National Blood Pressure study was used. Patients were followed for 4.1 (median) years and had eight (median) doctor visits during the study. SBP variability was defined as within-individual SD of SBP across study follow-up visits. RESULTS: Increased visit-to-visit SBP variability was found to be a strong predictor for future cardiovascular events in this elderly population. The hazard ratio (95% confidence interval) for any first fatal/nonfatal cardiovascular event for highest decile compared with lowest decile of SBP variability was 2.18 (1.52-3.13) after adjusting for sex, age, treatment including other baseline variables, and average on-treatment SBP. A similar effect was observed for stroke (hazard ratio 2.78, 1.28-6.05), myocardial infarction (hazard ratio 4.11, 1.87-9.06), and heart failure (hazard ratio 4.79, 1.82-12.62). Highest SBP variability was also a predictor of post-trial fatal cardiovascular events. Increased visit-to-visit SBP variability was related to age, pulse pressure, changing physicians, smoking, treatment allocation, and the use of multiple BP-lowering drugs. CONCLUSION: These findings suggest that reducing visit-to-visit SBP variability might be an important objective in addition to conventional blood pressure-lowering in elderly hypertensive patients.

Who's really hypertensive?--Quality control issues in the assessment of blood pressure for randomized trials.

The characterization of blood pressure in treatment trials assessing the benefits of blood pressure lowering regimens is a critical factor for the appropriate interpretation of study results. With numerous operators involved in the measurement of blood pressure in many thousands of patients being screened for entry into clinical trials, it is essential that operators follow pre-defined measurement protocols involving multiple measurements and standardized techniques. Blood pressure measurement protocols have been developed by international societies and emphasize the importance of appropriate choice of cuff size, identification of Korotkoff sounds, and digit preference. Training of operators and auditing of blood pressure measurement may assist in reducing the operator-related errors in measurement. This paper describes the quality control activities adopted for the screening stage of the 2nd Australian National Blood Pressure Study (ANBP2). ANBP2 is cardiovascular outcome trial of the treatment of hypertension in the elderly that was conducted entirely in general practices in Australia. A total of 54 288 subjects were screened; 3688 previously untreated subjects were identified as having blood pressure >140/90 mmHg at the initial screening visit, 898 (24%) were not eligible for study entry after two further visits due to the elevated reading not being sustained. For both systolic and diastolic blood pressure recording, observed digit preference fell within 7 percentage points of the expected frequency. Protocol adherence, in terms of the required minimum blood pressure difference between the last two successive recordings, was 99.8%. These data suggest that adherence to blood pressure recording protocols and elimination of digit preferences can be achieved through appropriate training programs and quality control activities in large multi-centre community-based trials in general practice. Repeated blood pressure measurement prior to initial diagnosis and study entry is essential to appropriately characterize hypertension in these elderly patients.

'Reverse white-coat hypertension' in older hypertensives.

OBJECTIVES: The role of ambulatory blood pressure monitoring (ABPM) in the elderly is unclear. This study has examined differences between clinic and ambulatory blood pressure (BP) in a large cohort of older hypertensives, with particular respect to the factors influencing the direction and magnitude of this difference. DESIGN: The Second Australian National Blood Pressure Study (ANBP2) is a general practice-based randomized-outcome trial in 6083 older hypertensives treated with an angiotensin-converting enzyme (ACE) inhibitor or diuretic-based regimen. Before starting treatment a subset of 713 patients (age range 65-83 years) had a 'successful' 26-hour ambulatory blood pressure recording with a SpaceLabs 90207 recorder. RESULTS: Average clinic BP (+/- SD) was 167 +/- 12/90 +/- 8 mmHg. Average daytime ambulatory BP was 157 +/- 15*/89 +/- 10* mmHg and night ambulatory BP was 137 +/- 16+/74 +/- 10+ mmHg (different from clinic BP: *P < 0.01;from daytime ambulatory BP: +P < 0.001). Twenty-one to 45% of all patients had higher daytime systolic or diastolic ambulatory BP than clinic readings, with smoking, previous treatment for hypertension and lower clinic BP being the main predictors of this 'reverse white-coat effect'. CONCLUSIONS: Although mean daytime ambulatory blood pressures were lower than clinic readings in this large cohort of untreated older hypertensives, a substantial proportion showed the reverse of the so-called 'white-coat effect'. These findings identify the important role for ABPM in the elderly, not only for avoiding overtreatment in those with typical 'white-coat hypertension' but also for ensuring adequate treatment is given to those with the reverse of this phenomenon.