Effect of aging on the prognostic significance of ambulatory systolic, diastolic, and pulse pressure in essential hypertension.

BACKGROUND: This study compared the relative prognostic significance of 24 hour intra-arterial ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP) parameters in middle-aged versus elderly hypertensives. METHODS AND RESULTS: A total of 546 subjects aged <60 years and 142 subjects aged >/=60 years who had undergone baseline pretreatment 24-hour intra-arterial ambulatory blood pressure monitoring were followed for 9.2+/-4.1 years. Multivariate analysis showed that in younger subjects, 24-hour, daytime, and nighttime DBP, MAP, and SBP, when considered individually, were positively related to morbid events; DBP parameters provided the best predictive values. In the group >/=60 years (elderly group), 24-hour, daytime, and nighttime PP and SBP were the most predictive parameters, whereas ambulatory DBP and MAP measurements failed to provide any prognostic value. When 24-hour values of SBP and DBP were jointly included in the baseline model, DBP (z=2.02, P=0.04) but not SBP (z=-0.43, P=0.67) was related to outcome in younger subjects, whereas in the elderly group, SBP (z=3.33, P=0.001) was positively and DBP (z=-1.75, P=0.07) was negatively related to outcome. Clinic blood pressure measurements failed to provide any independent prognostic value in either age group. CONCLUSIONS: The relative prognostic significance of ambulatory blood pressure components depends on age; DBP parameters provided the best prognostic value in middle-aged individuals, whereas PP parameters were the most predictive in the elderly. This may reflect differing underlying hemodynamic mechanisms of hypertension in these age groups.

Racial variation in cardiovascular morbidity and mortality in essential hypertension.

OBJECTIVES: To perform a longitudinal comparison of morbidity and mortality among white, south Asian and Afro-Caribbean hypertensive patients in relation to baseline demographic characteristics and clinic and ambulatory blood pressure variables. DESIGN: Observational follow up study. SETTING: District general hospital and community setting in Harrow, England. PATIENTS: 528 white, 106 south Asian, and 54 Afro-Caribbean subjects with essential hypertension who had undergone 24 hour ambulatory intra-arterial blood pressure monitoring. INTERVENTIONS: Follow up for assessment of all cause morbidity and mortality over a mean (SD) of 9.2 (4.1) years. MAIN OUTCOME MEASURES: Non-cardiovascular death, coronary death, cerebrovascular death, peripheral vascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation. RESULTS: South Asians had the highest all cause event rate of 3.46, compared with 2.50 (NS) and 0.90 (p = 0.002) events/100 patient-years for whites and Afro-Caribbeans, respectively. This was because of an excess of coronary events (2.86 v 1.32 events/100 patient-years in south Asians v whites, respectively; p = 0.002). Age (p < 0.001), sex (p < 0.001), race (south Asians : whites, hazard ratio 1.79; p = 0.008), diabetes (p = 0.05), previous history of cardiovascular disease (p < 0.001), and 24 hour ambulatory systolic blood pressure (p = 0.006) were independent predictors of time to a first event. Clinic blood pressure did not provide additional prognostic information. CONCLUSIONS: South Asian origin was an independent predictor of all cause events, mainly because of an excess of coronary events in this group. Ambulatory but not clinic blood pressure was of additional value in predicting subsequent morbidity and mortality.

Evidence-based medicine and hypertension.

BACKGROUND: Evidence-based medicine (EBM) has been propagated as a revolutionary development which will improve the quality of clinical decision-making and guideline development Historically it follows an early 19th-century French attempt to introduce mathematical analysis into clinical practice. This met with resistance from both clinicians and scientists and was only accepted in more recent times with the development of clinical epidemiology and clinical trials. NATURE OF EBM: EMB claims to utilize the best available evidence to reach scientific conclusions, rejecting the appeal to expert authority. This involves a hierarchy of sources which places large controlled trials at the apex. Less value is attributed to arguments from clinical observation or pathophysiology. Systematic reviews and meta-analyses of trials therefore provide the strongest evidence for clinical decisions. THE CONCEPT OF EVIDENCE: The approach advocated in EBM is an over-simplification of the process of clinical thinking which involves interpretation and synthesis of relevant evidence from all sources and extrapolation to the clinical situation. In this process, there is no hierarchy of evidence. The relative value given to any particular evidence depends more upon its relevance and persuasiveness than the category to which it belongs. Discussion and debate amongst informed 'experts' is an integral feature of this process at each stage. IMPACT OF EBM: Although advocates of EBM acknowledge the contribution of all forms of evidence, the differential value attached to different sources has led to naïve and simplistic attempts to omit the traditional processes of interpretation, synthesis and extrapolation and to draw wide-ranging conclusions from trial data without adequate scientific discussion.

Current clinical practice in hypertension: the EISBERG (Evaluation and Interventions for Systolic Blood pressure Elevation-Regional and Global) project.

Hypertension is one of the major treatable factors contributing to the burden of disease worldwide. However, despite national programs to encourage detection and treatment, there are still shortcomings in hypertension management. A large proportion of these can be attributed to socioeconomic factors, professional shortcomings, and patient noncompliance with management regimens. The Evaluation and Interventions for Systolic Blood pressure Elevation-Regional and Global (EISBERG) project was conceived to examine the reasons for suboptimal management of hypertension in more detail. Emphasis was placed on control of elevated systolic blood pressure because this is often neglected despite evidence that it is more important than diastolic pressure in predicting cardiovascular risk. The goals of the project include analysis of the relative importance of systolic and diastolic blood pressure as cardiovascular risk factors, identification of any necessary changes in practice, and the development and implementation of programs to promote appropriate changes in practice or attitudes. The three components of the initiative are a formal collection of epidemiologic evidence to examine the relation between systolic blood pressure and outcome; a cross-sectional, quantitative database (CardioMonitor) providing information on the treatment of patients with cardiovascular diseases including hypertension in seven countries, and qualitative research into hypertension management to assess attitudes, awareness, and knowledge among primary care physicians, patients and their carers. The study showed more effort was directed toward control of diastolic than systolic blood pressure. Adequate control of systolic blood pressure was seldom achieved. Blood pressure targets tended to be raised in elderly patients in conflict with recommendations and evidence that there is greater benefit in treating hypertension more aggressively in this population. Despite awareness of guidelines for treating hypertension, doctors were unsuccessful in practice.

Prediction of coronary and cerebrovascular morbidity and mortality by direct continuous ambulatory blood pressure monitoring in essential hypertension.

BACKGROUND: The goal of this study was to assess the prognostic value of ambulatory versus clinic blood pressure measurement and to relate cardiovascular risk to ambulatory systolic and diastolic blood pressure levels. METHODS AND RESULTS: The study population consisted of 688 patients 51+/-11 years of age who had undergone pretreatment 24-hour intra-arterial ambulatory blood pressure monitoring on the basis of elevated clinic blood pressure. A total of 157 first events were recorded during a 9.2+/-4.1-year follow-up period. The predictive value of a regression model containing age, sex, race, body mass index, smoking, diabetes mellitus, fasting cholesterol level, and previous history of cardiovascular disease was significantly improved by the addition of any ambulatory systolic or diastolic blood pressure parameter (whether 24-hour, daytime, or nighttime mean) or pulse pressure, whereas inclusion of baseline clinic blood pressure variables did not enhance the prediction of events. The most predictive models contained the ambulatory systolic blood pressure parameters. In the model containing 24-hour mean ambulatory systolic blood pressure (P=0.001), age (P<0.001), male sex (P<0.001), South Asian origin (P=0.008), diabetes mellitus (P=0. 05), and previous cardiovascular disease (P<0.001) were additional independent predictors of events. Whereas 24-hour ambulatory systolic blood pressure was linearly related to the incidence of both coronary and cerebrovascular events, 24-hour ambulatory diastolic blood pressure exhibited a positive linear relationship with cerebrovascular events but a curvilinear relationship with coronary events. CONCLUSIONS: Ambulatory blood pressure is superior to clinic measurement for the assessment of cardiovascular risk; there is no reduction in coronary risk at lower levels of ambulatory diastolic blood pressure.

Current status of hypertensive disease treatment: results from the Evaluation and Interventions for Systolic Blood pressure Elevation: Regional and Global (EISBERG) project.

Conclusive evidence has shown the benefits of antihypertensive treatment The systematic review of end-point trials has indicated that for a reduction of 10-12 mmHg in systolic blood pressure or 5-6 mmHg in diastolic blood pressure, the incidence of stroke is reduced by 38% and ischaemic heart disease by 16%. Despite this, studies on the effectiveness of treatment - carried out both in specialist hypertension clinics and in the community - have all shown that patients receiving treatment for hypertension continue to be at increased risk of cardiovascular disease. Failure to control blood pressure to recommended guidelines contributes substantially to this excess risk. Some reasons for this failure are outlined below. Socioeconomic factors and lack of professional and patient compliance appear to be of considerable importance in the failure to control blood pressure. The Evaluation and Interventions for Systolic Blood pressure Elevation: Regional and Global (EISBERG) project investigated both the quantitative and qualitative aspects of the current treatment of hypertension internationally. The quantitative study indicated major shortcomings in blood pressure control, and in particular, poor control of elevated systolic pressure, which accounted for 90% of treatment failures. The qualitative research was based upon semi-structured interviews with professionals, patients and their care-givers. These interviews indicated that there were misconceptions among physicians regarding the relative importance of systolic and diastolic blood pressure, the need for more aggressive treatment in the elderly, and the need for improved physician-patient interactions. If the therapeutic advances emerging from medical research are to be translated into clinical benefits, both the understanding and communication of the need for effective blood pressure control must be improved.

Value of ambulatory intra-arterial blood pressure monitoring in the long-term prediction of left ventricular hypertrophy and carotid atherosclerosis in essential hypertension.

The aim of this study was to compare the abilities of clinic and ambulatory blood pressure (BP) to predict the long term occurrence of left ventricular hypertrophy and carotid atherosclerosis in uncomplicated hypertensive patients. Two hundred and ninety-five patients who had undergone 24-h ambulatory intra-arterial BP monitoring on the basis of an elevated clinic BP, attended follow-up at a mean of 10.2 (+/- 3.5) years later. This consisted of a history, physical examination, risk factor profile and serum cholesterol level. Echocardiography and carotid ultrasonography were also performed to determine left ventricular mass index and maximal intima-media thickness (IMTmax), a measure of carotid atherosclerosis severity. The factors most strongly correlated with both left ventricular mass index and IMTmax were age, 24-h mean pulse pressure and 24-h mean systolic BP. Age, 24-h mean systolic BP and body mass index were independent correlates of left ventricular hypertrophy (R2 = 17%), whereas age, 24-h mean pulse pressure and pack years were independent predictors of carotid atherosclerosis (R2 = 34%). Clinic BP did not feature in the final model for the long term prediction of cardiovascular end-organ damage. These findings promote a role for ambulatory BP monitoring in guiding aggressiveness of drug therapy in an attempt to limit potential target organ damage.

Alcohol, blood pressure and hypertension.

In the last 30 years a large number of cross-sectional studies, a smaller number of prospective cohort studies and several intervention studies have addressed the alcohol-blood pressure relationship. Although a number of questions--such as the validity of measurement of alcohol intake, shape of the alcohol-blood pressure relationship, threshold dose for hypertension, and plausible pathophysiological mechanisms--have not yet been answered satisfactorily, it is clear that a causal association exists between chronic intake of > or = 30-60 g alcohol per day and blood pressure elevation in men and women. To call the alcohol-blood pressure relationship causal is justified because chance and, to a large degree, bias and confounding, have been ruled out as plausible explanations in most observational studies. More importantly, the intervention studies support the observational studies and show a remarkable consistency in demonstrating a potentially valuable decrease in blood pressure when heavy drinkers abstain or restrict their alcohol intake. From the different studies a rule of thumb can be derived: above 30 g of alcohol intake per day an increment of 10 g of alcohol per day increases on average systolic blood pressure by 1-2 mmHg and diastolic blood pressure by 1 mmHg.

Endothelial function in subcutaneous resistance arteries from elderly hypertensive and normotensive subjects.

1. Previous studies have indicated that younger hypertensive subjects may have abnormal endothelium-dependent relaxation, which could contribute to the elevated peripheral resistance seen in established hypertension. This study was designed to examine the functional behaviour of the endothelium of small arteries from elderly hypertensive and normotensive subjects. 2. Resistance arteries were obtained from gluteal biopsies taken under local anaesthesia in 28 subjects of mean age 70 (range 60-76) years, and studied in an isometric myograph. Eighteen subjects had untreated essential hypertension, and 10 were normotensive. 3. After measurement of the contractile response to noradrenaline, relaxation responses to a variety of endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (iloprost and sodium nitroprusside) mechanisms were assessed in vessels precontracted with noradrenaline. Endothelium-dependent responses were also studied after incubation with NG-nitro-L-arginine to inhibit nitric oxide synthase. 4. There were no significant differences in the contraction or relaxation responses between elderly subjects with or without high blood pressure. Inhibition of nitric oxide synthase prevented any relaxation with acetylcholine and significantly attenuated the relaxation with bradykinin. Near-complete relaxation was however achieved with the endothelium-independent vasodilator sodium nitroprusside. 5. Hypertension in elderly subjects is not associated with a reduction in endothelial vasodilating function in the subcutaneous vessels of the gluteal region compared with age-matched normotensive controls. The results of this study do not support the hypothesis of a defect of resistance artery endothelium-dependent relaxation in the pathophysiology of hypertension in the elderly.

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index.

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.

Clinical trials: what more is needed? A critical view.

TRADITIONAL DIVISIONS OF MEDICAL RESEARCH: Medical research has been traditionally classified as "basic' and "applied'. The latter category has tended to emphasize the value of randomized controlled trials. These, however, cannot be applied to routine clinical care without considerable extrapolation. There is a further need for research into optimal methods of health care delivery directed at improving the standards of treatment and taking account of such factors as socio-economic need and barriers to access. REQUIREMENT FOR AN INTEGRATED PROGRAMME OF RESEARCH: If the full opportunities offered by scientific research are to be exploited, an integrated programme of research is required which extends from the basic to the applied and which recognizes the traditional, end-point, controlled trial as only one component in a spectrum of scientific activity.