L. Hansson

STOP-Hypertension 2: a prospective intervention trial of "newer" versus "older" treatment alternatives in old patients with hypertension. Swedish Trial in Old Patients with Hypertension.

It is well established that hypertensive patients benefit from drug treatment of their disorder. In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits, i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity. In all these studies beta-blockers and/or diuretics were used in comparison with placebo. Newer therapeutic alternatives have, however, at least theoretically, many advantages which could result in further improvements in prognosis. The initial Swedish Trial in Old Patients with Hypertension (STOP-Hypertension 1) was conducted in men and women aged 70-84 years. STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors (enalapril and lisinopril) or on calcium antagonists (isradipine and felodipine), using the PROBE design (Prospective, Randomised, Open, Blinded Endpoint evaluation). The primary aim will be to assess the effect on cardiovascular mortality. Statistical calculations indicate that 6,600 patients, followed for four years will be needed (2p < 0.05, power 90%) to obtain significance if there is a 25% difference between the new and the established therapy. Patients in primary health care (300 centres) will be included if their supine blood pressure is > or = 180/105 mmHg (and/or). Recruitment of patients started in September 1992 and so far more than 100 patients/week have been included.

The cost‐effectiveness of treating hypertension in elderly people—an analysis of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension)

Abstract. Objectives. The aim of this study was to estimate the cost‐effectiveness of antihypertensive treatment in elderly people based on the results of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension).

Cystatin C—A marker of peripheral atherosclerotic disease?

UNLABELLED It has been suggested that Cystatin C, besides its function as a marker of glomerular filtration, could be an independent marker of cardiovascular disease. However, studies on this topic are few and results have been indecisive. Our aim was to further investigate the subject of Cystatin C as an independent marker of peripheral atherosclerotic disease. METHOD Blood samples were analysed for serum Cystatin C, IL6, CRP and creatinine in 103 males with peripheral arterial disease (PAD) and 96 controls matched for age and sex. Creatinine clearance (CCr) was calculated according to Cockcrofts formula and estimated glomerular filtration rate (eGFR) was calculated according to MDRD formula. RESULTS Cystatin C-concentration was higher in PAD-patients compared to controls; 1.09+/-0.40 vs. 0.95+/-0.17 mg/L (p<0.01). There was no difference in CCr; 81+/-27 vs. 82+/-22 mL/min or eGFR; 76+/-21 vs. 79+/-14 mL/min. Cystatin C correlated to CCr, logIL-6 and logCRP in both patients (r=-0.60, p<0.001), (r=0.35, p<0.001) and (r=0.30, p<0.01) and controls (-0.44, p<0.001), (0.38, p<0.001) and (r=0.32, p<0.01), respectively. In an analysis of covariance, corrected for difference in eGFR, Cystatin C remained higher in PAD-patients compared to controls; 1.09 (C.I. 1.04-1.14) vs. 0.96 (C.I. 0.90-1.01). CONCLUSION Cystatin C-concentration, corrected for differences in eGFR, IL-6 and CRP values, is higher in PAD-patients compared to controls. Our finding suggests that Cystatin C may be an independent marker of atherosclerotic disease apart from its relation to kidney function.

Health economics in the Hypertension Optimal Treatment (HOT) study: costs and cost‐effectiveness of intensive blood pressure lowering and low‐dose aspirin in patients with hypertension

Abstract.  Jönsson B, Hansson L, Stålhammar N‐O (Stockholm School of Economics, Stockholm; University of Uppsala, Uppsala, Sweden; and AstraZeneca Pharmaceuticals, DE, USA). Health economics in the Hypertension Optimal Treatment (HOT) study costs and cost‐effectiveness of intensive blood pressure lowering and low‐dose aspirin in patients with hypertension. J Intern Med 2003; 253: 472–480.

A 5-year prospective, observational study of the withdrawal of antihypertensive treatment in elderly people

Abstract. Objectives. To observe blood pressure, cardiovascular events, and total mortality after withdrawing antihypertensive treatment for elderly patients.

Influence of age, sex and blood pressure on the principal endpoints of the Nordic Diltiazem (NORDIL) Study

Background The aim of the Nordic Diltiazem (NORDIL) Study was to compare patients with essential hypertension receiving calcium-antagonist-based treatment with diltiazem and similar patients receiving conventional diuretic/β-blocker-based treatment, with respect to cardiovascular morbidity and mortality. Objective To assess the influence of age, sex, severity of hypertension and heart rate on treatment effects, in a sub-analysis. Methods The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled, at health centres in Norway and Sweden, 10 881 patients aged 50–74 years who had diastolic blood pressure (DBP) of 100 mmHg or more. Systolic blood pressure (SBP) and DBP were decreased by 20.3/18.7 mmHg in the diltiazem group and by 23.3/18.7 mmHg in the diuretic/β-blocker group – a significant difference in SBP (P < 0.001). Results The incidence of the primary endpoint – a composite of cardiovascular death, cerebral stroke and myocardial infarction – was similar for the two treatments. Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 patients in the conventional treatment group [relative risk (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99;P = 0.040], whereas there was a non-significant inverse tendency with respect to all myocardial infarction. There were significantly fewer cerebral strokes in patients receiving diltiazem in the subgroups with baseline SBP > 170 mmHg (n = 5420, RR 0.75, 95% CI 0.58 to 0.98;P = 0.032), DBP ⩾ 105 mmHg (n = 5881, RR 0.74, 95% CI 0.57 to 0.97;P = 0.030) and pulse pressure ⩾ 66 mmHg (n = 5461, RR 0.76, 95% CI 0.58 to 0.99, P = 0.041), and more myocardial infarctions in those with heart rate less than 74 beats/min (n = 5303, RR 1.13, 95% CI 1.01 to 1.87;P = 0.040). However, the tendencies for fewer strokes and greater incidence of myocardial infarction were present across subgroups when results were analysed for age, sex, severity of hypertension and heart rate, and treatment–subgroup interaction analyses were not statistically significant. Conclusions Compared with a conventional diuretic/β-blocker-based antihypertensive regimen, there were additional 25% reductions in stroke in the diltiazem-treated patients with blood pressure or pulse pressure greater than the medians, and an increase in myocardial infarction in those with heart rate less than the median. Such findings may be attributable to chance, but the consistency of, in particular, the stroke findings may also suggest an ability of diltiazem, beyond conventional treatment, to prevent cerebral stroke in hypertensive patients with the greatest cardiovascular risk.

Plasma NT‐proBNP concentration is related to ambulatory pulse pressure in peripheral arterial disease

Background. Increased levels of N‐terminal prohormone brain natriuretic peptide (NT‐proBNP) are associated with left ventricular dysfunction (LVD) and left ventricular hypertrophy (LVH), but the relation of NT‐proBNP to ambulatory blood pressure (ABP) and hypertensive target organ damage in high‐risk patients with peripheral arterial disease (PAD) has not been studied. We hypothesized that NT‐proBNP levels were increased in patients with PAD in comparison to a matched control group and that levels of NT‐proBNP were related to ABP. Methods. Blood samples were analysed for NT‐proBNP in 103 males with PAD and 96 age‐ and sex‐matched controls. Ninety‐eight PAD patients performed ABP monitoring and 99 underwent Tc‐99m Sestamibi myocardial perfusion SPECT. Results. NT‐proBNP was significantly increased in PAD patients compared with controls [median (interquartiles)] 167(76, 418) vs 68(38, 142) pg/ml, p<0.001. Plasma levels of NT‐proBNP correlated positively to systolic blood pressure (SBP), pulse pressure (PP), night–day ratio of SBP and showed the strongest correlation to average night PP (r = 0.42, p<0.001). In multiple regression analysis, night PP remained independently related to NT‐proBNP. Conclusion. NT‐proBNP levels are markedly increased in PAD patients compared to age‐matched controls. Night PP is related to NT‐proBNP levels independently of other variables highlighting the importance of ambulatory PP as a cardiovascular risk factor. Measurement of NT‐proBNP could be indicated in PAD patients for further risk stratification.

Measurement of C-reactive protein and the erythrocyte sedimentation rate in general practice.

OBJECTIVE To evaluate the NycoCard:::CRP test (Nycomed A/S, Oslo, Norway) in relation to ESR in consecutive patients in general practice. NycoCard:::CRP test was also compared with a reference method for CRP quantitation. DESIGN C-reactive protein and ESR were simultaneously measured in 607 consecutive patients at four community health centres. SETTING Four community health centres in southern Sweden. RESULTS We obtained consistent results in 71% of the cases. In 20% CRP was increased more than ESR, while ESR was increased more than CRP in 9%. CRP was increased in 16% while ESR was below the upper reference limit for age and sex. On the other hand ESR was increased while CRP was below 10 mg/l in five % of the patients. In most of the cases where there was a discrepancy- for example, in infectious diseases-the CRP results were more clear-cut. Using the NycoCard test the CRP concentration can be measured directly in a whole blood sample with the result available within minutes. Comparison of the NycoCard:::CRP test with the reference method for CRP quantitation showed good agreement. CONCLUSION In clinical situations with suspected inflammatory diseases, the CRP test appears often to yield more useful results than the ESR. The NycoCard:::CRP test is suitable for use in general practice.

Study on COgnition and Prognosis in the Elderly (SCOPE): Design and Objectives

Hypertension is a major risk factor for cardiovascular events, including stroke, as well as for white matter lesions of the brain. There is also evidence to link cognitive impairment and dementia to hypertension. However, it has not been established whether antihypertensive treatment of elderly patients with a diastolic blood pressure (DBP) in the range 90-99 mmHg provides protection against major cardiovascular events and cognitive impairment. The Study on COgnition and Prognosis in the Elderly (SCOPE) is the first study designed to assess the effects of antihypertensive drug treatment on major cardiovascular events and cognitive function in elderly patients with mild hypertension. SCOPE is a prospective, randomized, double-blind, parallel comparison of the effects of the angiotensin II type 1 (AT 1 ) receptor blocker candesartan cilexetil and placebo on major cardiovascular events (myocardial infarction [MI], stroke and cardiovascular death), cognitive function as measured by the Mini-Mental State Examination (MMSE), quality of life (QoL) and health economics. The study has included both men and women, aged 70-89 years of age, with systolic blood pressure (SBP) of 160-179 mmHg and/or DBP of 90-99 mmHg and an MMSE score of 24 or above. Nearly 5000 patients have been recruited and will be followed for a mean period of 2.5 years. After a run-in period of 1-3 months, patients were randomized to receive placebo or candesartan cilexetil, 8 mg once daily, which has been shown to provide effective and long-lasting blood pressure reductions, while maintaining placebo-like tolerability, in elderly patients. All previous antihypertensive treatment was standardized to hydrochlorothiazide (HCTZ), 12.5 mg, at enrolment. At any time during the study, the dose of study drug will be doubled if SBP rises above 160 mmHg or DBP rises above 85 mmHg. If an SBP above 160 mmHg or a DBP above 90 mmHg is observed despite the increase in study medication, additional antihypertensive medication with HCTZ is recommended. Assessments to be made during the study will include blood pressure, heart rate, ECG, MMSE, health economics and QoL. Data on adverse events and clinical events will also be collected throughout the study. SCOPE is organized and co-ordinated by an Executive Committee, a Steering Committee, an Independent Safety Committee, an Independent Event Committee and a Co-ordinating Centre. Countries participating in the Study include Belgium, Canada, Finland, France, Germany, UK, Hungary, Israel, Norway, Poland, Portugal, Spain, Sweden, The Netherlands and the USA. Inclusion of patients was completed in January 1999 and at that time 4964 patients were randomized. The baseline characteristics of these patients are shown in the Table.