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H Wedel

Publications and source records attributed to H Wedel.

At least 55 records · Page 3Linked to original sources
PubMed1999

Body weight and weight gain during adult life in men in relation to coronary heart disease and mortality. A prospective population study.

AIMS: To assess the risk of death from coronary disease, and all causes associated with body mass index and weight gain from age 20 to middle age. METHODS AND RESULTS: In this study, 6874 men aged 47 to 55 years at baseline and free of a history of myocardial infarction were followed with respect to mortality from coronary disease and from all causes over an average follow-up of 19.7 years, and with respect to non-fatal myocardial infarction for 11.8 years. High body mass index predicted death from coronary disease, but only at levels above 27.5 m.kg-2. Men with stable weight (defined as +/- 4% change from age 20) had the lowest death rate from coronary disease and the lowest risk of non-fatal myocardial infarction. Relative risk of coronary death increased with increasing weight gain, from 1.57 (1.14-2.15) (after adjustment for age, physical activity, and smoking) in the group who gained 4 to 10%, to 2.76 (1.97-3.85) in men with a weight gain of more than 35% (P for trend 0.0001), compared to men who remained stable. After further adjustment for serum cholesterol, systolic blood pressure, and diabetes, relative risks were reduced but still significantly elevated in all weight gain groups (P for trend 0.004). Data concerning non-fatal myocardial infarction were available for the first 11.8 years and showed a relative risk of 3.35 (2.05-5.47) after adjustment for age, physical activity, and smoking in men with a weight gain of more than 35%. CONCLUSION: Weight gain from age 20, even a very moderate increase, is strongly associated with an increased risk of coronary death and non-fatal myocardial infarction.

Adult↗
PubMed1998

Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.

BACKGROUND: Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension. METHODS: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo. FINDINGS: Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001). INTERPRETATION: Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.

Aged↗
PubMed1998

Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. METHODS AND RESULTS: The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients.

Adult↗
PubMed1998

[Is antihypertensive treatment a risk factor of coronary disease? Therapy-related triglyceride increase nor diabetes increase the risk].

In an observational study designed to determine whether metabolic changes during long-term antihypertensive drug treatment are associated with an increased risk of coronary heart disease (CHD), 686 middle-aged hypertensive men recruited from a random population screening sample were followed up for 15 years. Antihypertensive treatment predominantly consisted of beta-adrenoceptor blockers and/or thiazide diuretics. CHD and diabetes mellitus were checked for at annual examinations. Time-dependent Cox regression analysis was used to determine correlation between the incidence of CHD and entry characteristics, the monitored serum levels of cholesterol and triglyceride concentrations and the development of diabetes mellitus. Univariate analysis showed the presence of diabetes mellitus a entry to the study and increased baseline serum concentrations of cholesterol and of triglycerides each to be a significant predictor of CHD, the respective relative risks (RR) being 2.12, 1.21 and 1.21. However, analysis of monitored levels of metabolic variables during follow-up showed only an increased serum cholesterol concentration to be significantly and independently associated with CHD (RR 1.07). Although serum triglyceride concentrations increased slightly during follow-up, they were unrelated to the incidence of CHD; nor was onset of diabetes mellitus during follow-up significantly associated with an increased risk of CHD (RR 1.48. Thus, the study showed the presence of metabolic disturbances such as diabetes mellitus and hyperlipidaemia before the start of antihypertensive treatment to be of positive predictive value in middle-aged hypertensive men, and an increase in the monitored serum cholesterol level to be an independent predictor of CHD, whereas neither drug-related diabetes nor an increase in the monitored serum triglyceride concentration seemed to be associated with the occurrence of CHD.

Adrenergic beta-Antagonists↗
PubMed1998

Hypertension and long-term cancer incidence and mortality among Swedish men.

OBJECTIVE: To examine incidence of cancer and cancer mortality in relation to high blood pressure. DESIGN: A longitudinal study of middle-aged men from a random population sample. SETTING: Göteborg, Sweden. SUBJECTS: We studied 7396 men aged 47-55 years without diagnosed cancer at baseline (1970-1973). MAIN OUTCOME MEASURES: Incidence of cancer and mortality from cancer. RESULTS: By the end of December 1992, 1401 men had been diagnosed with cancer at any site and 651 had died from cancer. Of the men in the highest fifth of the systolic blood pressure distribution (above 166 mmHg) 126 per 10000 observation years were diagnosed with cancer at any site, compared with 91 per 10000 in the lowest fifth [below 130 mmHg; relative risk after adjustment for age, smoking, body mass index, treatment for hypertension and leisure time physical activity 1.41 (95% confidence interval 1.19-1.68); P for trend 0.0001]. Of men in the highest fifth, 55 per 10000 observation years died from cancer, compared with 42 in the lowest [adjusted relative risk 1.41 (1.09-1.82); P for trend 0.01]. Several types of tumour tended to be more common among men with hypertension, but only genito-urinary cancers [age-adjusted relative risk 1.39 (1.04-1.85)] and non-melanoma skin cancer [age-adjusted relative risk 1.98 (1.12-3.51)] were significantly so. Findings were similar for diastolic blood pressure and if data for the first 5 years of follow-up were excluded. There was an increase in risk of cancer also during the first 5 years [adjusted relative risk 1.80 (1.10-2.92) for systolic blood pressure and 1.77 (1.05-2.99) for diastolic blood pressure]. CONCLUSIONS: We found an excess risk of cancer and of death from cancer for men with high blood pressure. Although the increase in risk was comparatively modest, the findings are of public health importance, insofar as both hypertension and cancer are common conditions.

Aged↗
PubMed1998

Natural history of myocardial infarction and angina pectoris in a general population sample of middle-aged men: a 16-year follow-up of the Primary Prevention Study, Göteborg, Sweden.

OBJECTIVES: Although many studies have described prognosis in patients with coronary heart disease (CHD), few have compared outcome in men with clinical evidence of CHD with healthy men from the general population over an extended follow-up. This study aimed to compare long-term prognosis in men with a history of myocardial infarction (MI) and in men with angina pectoris (AP) without MI, with men without clinical signs of CHD. DESIGN: Longitudinal general population study. SETTING: City of Göteborg, Sweden. SUBJECTS: From a general population sample, 195 men who had survived an MI for 0-19 years (median 3 years) and 314 men with AP but no MI (uncomplicated AP) at baseline in 1974-77 were identified and compared with 6591 men without clinical coronary disease. All were aged 51-59 years. Incident non-fatal and fatal cases occurring until the beginning of 1983 were also followed (n = 317). MAIN OUTCOME MEASURES: Death from CHD, from other causes and from all causes during a follow-up of at least 16 years. RESULTS: Overall survival was 72% amongst men without coronary disease, 53% amongst men with uncomplicated AP and 34% amongst men with past MI at baseline. In survivors of MI the risk-factor-adjusted relative risk (RR) of coronary death during follow-up was 6.67 (95% confidence interval (CI) 5.29-8.39), of dying from non-cardiovascular causes 1.35 (0.96-1.91), and of dying from any cause 3.20 (2.67-3.83). During the first 4 years after the baseline examination, the adjusted RR of CHD death was 15.96 (10. 29-24.74), and of dying from any cause 5.22 (3.68-7.41). During the last 4 years of follow-up, relative risk was still 5.87 (3.44-10.01) for CHD death and 2.93 (2.05-4.18) for death from any cause. In men with uncomplicated AP, the adjusted relative risk of CHD death during the first 4 years was 4.05 (2.27-7.22) and 3.23 (2.10-4.96) during the last 4-year period. After the first year, the incident MI cases had the same average annual mortality (about 5%) as the prevalent cases. CONCLUSIONS: In survivors of MI, mortality risk remained high even after an extended follow-up. Men with angina had a better prognosis, but still a compromised survival compared with the general population.

Angina Pectoris↗
PubMed1998

Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint Reduction in Hypertension.

-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.

Aged↗
PubMed1998

Changes in estimated coronary risk in the 1980s: data from 38 populations in the WHO MONICA Project. World Health Organization. Monitoring trends and determinants in cardiovascular diseases.

The World Health Organization (WHO) MONICA Project is a 10-year study monitoring trends and determinants of cardiovascular disease in geographically defined populations. Data were collected from over 100,000 randomly selected participants in two risk factor surveys conducted approximately 5 years apart in 38 populations using standardized protocols. The net effects of changes in the risk factor levels were estimated using risk scores derived from longitudinal studies in the Nordic countries. The prevalence of cigarette smoking decreased among men in most populations, but the trends for women varied. The prevalence of hypertension declined in two-thirds of the populations. Changes in the prevalence of raised total cholesterol were small but highly correlated between the genders (r = 0.8). The prevalence of obesity increased in three-quarters of the populations for men and in more than half of the populations for women. In almost half of the populations there were statistically significant declines in the estimated coronary risk for both men and women, although for Beijing the risk score increased significantly for both genders. The net effect of the changes in the risk factor levels in the 1980s in most of the study populations of the WHO MONICA Project is that the rates of coronary disease are predicted to decline in the 1990s.

Adult↗
PubMed1997

Cost effectiveness of simvastatin treatment to lower cholesterol levels in patients with coronary heart disease. Scandinavian Simvastatin Survival Study Group.

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) showed that lowering cholesterol levels with simvastatin reduces mortality and morbidity in patients with angina pectoris or previous acute myocardial infarction. Before the widespread use of cholesterol-lowering drugs in such patients is recommended, its cost effectiveness should be demonstrated. We estimated the cost effectiveness of simvastatin treatment to lower cholesterol levels in relation to the age, sex, and cholesterol level before treatment of patients with coronary heart disease. METHODS: We estimated the cost per year of life gained with simvastatin therapy. To model the increased life expectancy, hazard functions from 4S were used. The costs studied included those of the intervention and the direct and indirect costs associated with morbidity from coronary causes. We prepared separate estimates for men and women at various ages (from 35 to 70 years) and total cholesterol levels before treatment (213 to 309 mg per deciliter). RESULTS: In the analysis limited to direct costs, the cost of each year of life gained ranged from $3,800 for 70-year-old men with 309 mg of cholesterol per deciliter to $27,400 for 35-year-old women with 213 mg of cholesterol per deciliter. When we included indirect costs, the results ranged from a savings in the youngest patients to a cost of $13,300 per year of life gained in 70-year-old women with 213 mg of cholesterol per deciliter. CONCLUSIONS: In patients with coronary heart disease, simvastatin therapy is cost effective among both men and women at the ages and cholesterol levels studied.

Adult↗
PubMed1997

Mortality prediction in diabetic patients with myocardial infarction: experiences from the DIGAMI study.

OBJECTIVES: We analysed predictors of 1-year mortality following acute myocardial infarction in patients with diabetes mellitus by applying uni- and multivariate statistics on the DIGAMI cohort. BACKGROUND: Diabetic patients with acute myocardial infarction have a poor prognosis. This may depend on a poor metabolic control, a hypothesis that was tested in DIGAMI, a prospective randomised study. In this trial institution of immediate intensive insulin treatment reduced 1-year mortality by 30%. METHODS: We recruited 620 diabetic patients with acute myocardial infarction, 314 of whom served as controls, while the remaining 306 patients were treated with an acute insulin-glucose infusion followed by multidose subcutaneous insulin. RESULTS: Age, previous myocardial damage, duration of the diabetes and previous insulin therapy were significantly related to 1-year mortality, while conventional risk factors lacked independent prognostic weight. Female sex was not linked to mortality when controlling for the confounding effects of other predictors. One of the strongest predictors of a fatal outcome, in particular during the hospital phase, was blood glucose at hospital admission. Beta-blockade appeared to exert a striking, independent secondary-preventive effect. CONCLUSIONS: It seems that good metabolic control and not conventional risk factors is of major importance for diabetic patients sustaining acute myocardial infarction. Also treatment with beta-blockade seems to be of special importance in this category of patients.

Adrenergic beta-Antagonists↗
PubMed1997

Perinatal outcome after leave of absence from work for twin-pregnant women.

AIM: To evaluate the association between the incidence of leave of absence from work and perinatal outcome for the twin-pregnant woman. MATERIAL AND METHODS: A 20.2% sample of all twin-pregnant women between 1982 and 1988 (1,331/6,602) was taken at random from the entire material of twin deliveries in Sweden, archived at the Medical Birth Registry (MBR), National Board of Health and Welfare. For each woman in the sample, information on period(s) and reasons for leave of absence from work during pregnancy was obtained by inquiry to all Regional Health Insurance Offices throughout Sweden. A comparison of perinatal outcome was also made with information from the Danish Fertility Database and the Norwegian Medical Birth Registry. RESULTS: Duration of leave from work increased from 58 days in 1982 to 97 days in 1988 (trend analysis; t = 7.9, p < 0.001). No association was seen between perinatal mortality for twins weighing < 1,500 g and changes in the incidence of leave of absence. The incidence of twins with a birthweight < 1,500 g varied among the three countries, increasing significantly only in Sweden (trend analysis chi 2 = 20.3, p < 0.0001). CONCLUSION: Although the number of days of leave of absence increased by 60%, there was no obvious association with perinatal mortality for twins weighing < 1,500 g. The incidence of Swedish twins with a birthweight < 1,500 g increased significantly, indicating that the effect of leave of absence from work on perinatal outcome may be less effective than previously thought.

Female↗
PubMed1997

Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency.

BACKGROUND: Chronic renal insufficiency is accompanied by specific alterations of the lipoprotein metabolism. It has been suggested that the renal dyslipoproteinaemia of renal insufficiency contributes to the progression of glomerular and tubular lesions, with subsequent deterioration of renal function. The objective of this prospective study was to investigate whether the specific lipoprotein abnormalities of renal insufficiency are associated with the rate of decline of renal function in patients with moderately advanced chronic renal failure. METHODS: A patient population of 73 adult non-diabetic patients with primary chronic renal disease were followed with repeated measurements of the glomerular filtration rate (GFR) for an average of 3.2 (SD 0.7) years. Forty-three of these patients had chronic glomerulonephritis as the underlying renal disease. Patient characteristics including plasma levels of lipids and apolipoproteins were determined at entry and were prospectively related, using linear regression, to the rate of progression. RESULTS: The mean GFR at entry was 41.3 (SD 15.3) ml/min x 1.73 m2 BSA. The average rate of progression was a decline in GFR of -2.8 (SD 3.7) ml/min x 1.73 m2 BSA per year. In the whole patient study group total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B (apoB) were all significantly associated with a more rapid decline in renal function, whereas triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein A (apoA) were not. In the more homogeneous subgroup of patients with chronic glomerulonephritis the association between dyslipidaemia and the rate of progression was even more pronounced. In this subgroup of patients also serum triglycerides and apoE were significantly associated with a higher rate of progression. Both the initial blood pressure and proteinuria were also significantly associated with a more rapid decline in renal function in the whole study group as well as in patients with chronic glomerulonephritis. The associations between these variables with the rate of progression were all independent of the entry GFR values. CONCLUSIONS: These results indicate that the lipoprotein abnormalities of renal insufficiency contribute to the progression of renal failure in human chronic renal disease.

Adult↗
PubMed1997

Serum cholesterol and long-term prognosis in middle-aged men with myocardial infarction and angina pectoris. A 16-year follow-up of the Primary Prevention Study in Göteborg, Sweden.

OBJECTIVE: To compare the role of serum cholesterol in the long-term prognosis of men with a history of myocardial infarction, in men with clinical angina without myocardial infarction, and men without clinical coronary disease. METHODS: In the second screening of the Primary Prevention Study in Göteborg which comprised 7100 men aged 51 to 59 years at baseline in 1974-1977, 314 men with clinical angina but no myocardial infarction at baseline were identified and 195 men who had survived a myocardial infarction for 0 to 19 years (median 3 years). RESULTS: Of the men without clinical coronary disease at baseline and cholesterol at or below 5.2 mmol.l-1, 2.7 per 1000 observation years died from coronary disease compared to 8.5 per 1000 of the men with serum cholesterol of 7.2 mmol.l-1 or more. Corresponding figures for men with angina was 5.5 and 31.0 per 1000 observation years, and for men with prior myocardial infarction 19.8 and 58.3, respectively, per 1000. After adjustment for age, smoking, systolic blood pressure, body mass index and diabetes the risk of coronary death in men with serum cholesterol above 7.2 mmol.l-1 compared to below 5.2 mmol.l-1 was 2.42 (1.66-3.51) in healthy men, 4.82 (1.44-16.09) in men with angina, 2.70 (0.95-7.67) in survivors of myocardial infarction, and 4.07 (1.86-8.91) in the combined group of men with either angina or prior infarction. The strongest effect was seen during the first half of the follow-up, with an adjusted relative risk for high in relation to low serum cholesterol of 8.08 (1.95-33.55) in men with preexisting coronary disease. Non-coronary deaths varied little by serum cholesterol or coronary disease status at baseline. After 16 years, 76% of the healthy men with low cholesterol and 65% of healthy men with cholesterol above 7.2 mmol.l-1 were still alive. Of the men with prior myocardial infarction, 50% in the group with low cholesterol were alive after 16 years, as compared to 21% of those with high cholesterol. CONCLUSION: The long-term absolute risk of death in men with coronary disease and elevated serum cholesterol is very high. Implementation of lipid-lowering strategies shown to be efficacious is important in this high-risk group.

Angina Pectoris↗
PubMed1997

The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group.

The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity, largely due to a decreased incidence of stroke, whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies. Furthermore, treated hypertensive patients still have a higher cardiovascular complication rate, compared with matched normotensives. This is particularly evident in patients with left ventricular hypertrophy (LVH), a major independent risk indicator for cardiovascular disease. In addition to elevating blood pressure, angiotensin II (A-II) exerts an important influence on cardiac structure and function, stimulating cell proliferation and growth. Thus, to further reduce morbidity and mortality when treating hypertensive patients, it may be important to effectively block the effects of A-II. This can be achieved directly at the A-II receptor level by losartan, the first of a new class of antihypertensive agents. It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy, and thus improves prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients (initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg) with electrocardiographically documented LVH. The study, which will continue for at least 4 years and until 1,040 patients experience one primary endpoint, has been designed with a statistical power that will detect a difference of at least 15% between groups in the incidence of combined cardiovascular morbidity and mortality. It is also the first prospective study with adequate power to link reversal of LVH to reduction in major cardiovascular events. The rationale of the study, which will involve more than 800 clinical centers in Scandinavia, the United Kingdom, and the United States, is discussed, and the major features of its design and general organization are described. On April 30, 1997, when inclusion was stopped, 9,218 patients had been randomized.

Adrenergic beta-Antagonists↗
PubMed1996

Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study.

BACKGROUND: Long-term safety is an important consideration in the selection and use of drugs, such as lipid-lowering agents, that are prescribed to reduce the risk of clinical events during long periods. METHODS: The Scandinavian Simvastatin Survival Study was designed to evaluate the effects of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with angina pectoris or previous myocardial infarction and serum cholesterol levels of 5.5 to 8.0 mmol/L (213-310 mg/dL) receiving a lipid-lowering diet were randomly assigned to take double-blind treatment with simvastatin, 20 to 40 mg once daily, or placebo. In addition to previously reported end-point events, detailed clinical and laboratory safety data were collected during a median follow-up period of 5.4 years (range in survivors, 4.9-6.2 years). RESULTS: The only clearly drug-related serious adverse event during the 5.4-year median follow-up period was a single reversible case of myopathy. The frequencies of persistent elevations of hepatic aminotransferase levels above 3 times the upper limit of normal and of nonviral hepatitis in the simvastatin and placebo treatment groups were not significantly different. Examination of the lens showed no between-group differences, and no previously unrecognized adverse effects of the drug were observed. There were no significant between-group differences in adverse events in any body system. In particular, the frequency of adverse events related to the central nervous system was similar in both groups. CONCLUSION: The safety profile of simvastatin, 20 to 40 mg daily, over 5 years was excellent.

Adult↗
PubMed1996

Diabetes mellitus and raised serum triglyceride concentration in treated hypertension--are they of prognostic importance? Observational study.

OBJECTIVE: To analyse whether metabolic changes during long term treatment with antihypertensive drugs are associated with an increased risk of coronary heart disease. DESIGN: Observational study. SETTING: Gothenburg, Sweden. SUBJECTS: 686 middle aged hypertensive men, recruited after screening of a random population sample, and followed for 15 years during treatment with predominantly beta adrenoceptor blockers or thiazide diuretics, or both. Coronary heart disease and diabetes mellitus were registered at yearly patient examinations. Entry characteristics, as well as within study serum concentrations of cholesterol and triglycerides and the development of diabetes mellitus, were related to the incidence of coronary heart disease in a time dependent Cox's regression analysis. MAIN OUTCOME VARIABLE: Coronary heart disease morbidity. RESULTS: Diabetes mellitus, raised serum cholesterol and triglyceride concentrations present at the beginning of the study were all significantly predictive of coronary heart disease in univariate analysis. The relative risk of diabetes mellitus and of a 1 mmol/l increase in the cholesterol and triglyceride concentrations was 2.12 (95% confidence interval 1.11 to 4.07), 1.21 (1.05 to 1.39), and 1.21 (1.03 to 1.43) respectively. However, when the within study metabolic variables were analysed, only the serum cholesterol concentration was significantly and independently associated with coronary heart disease (relative risk 1.07 (1.02 to 1.13)). Although the triglyceride concentrations increased slightly during the follow up, the within study serum triglyceride concentrations were not associated with the incidence of coronary heart disease (1.04 (0.96 to 1.10)). New diabetes mellitus-that is, onset during follow up-was not significantly associated with an increased risk for coronary heart disease (1.48 (0.37 to 6.00)). CONCLUSIONS: Metabolic disturbances such as diabetes mellitus and hyperlipidaemia presenting before the start of antihypertensive treatment have a prognostic impact in middle aged, treated hypertensive men. Moreover, while within study cholesterol concentration was an independent predictor of coronary heart disease, drug related diabetes mellitus and raised serum triglyceride concentrations that are associated with treatment do not seem to have any major impact on the coronary heart disease prognosis in this category of patients.

Adrenergic beta-Agonists↗