Incidence of Type 2 diabetes among occupational classes in Sweden: a 35-year follow-up cohort study in middle-aged men.

AIMS: To assess if low occupational class was an independent predictor of Type 2 diabetes in men in Sweden over a 35-year follow-up, after adjustment for both conventional risk factors and psychological stress. METHODS: A random population-based sample of 6874 men aged 47-56 years without a history of diabetes was divided into five occupational classes and the men were followed from 1970 to 2008. Diabetes cases were identified through the Swedish inpatient and death registers. Subdistribution hazard ratios (SHRs) and 95% CIs from competing risk regressions, cumulative incidence and conditional probabilities were calculated, after accounting for the risk of death attributed to other causes. RESULTS: A total of 907 (13%) men with diabetes were identified over 35 years with a median follow-up of 27.9 years. The cumulative incidence of diabetes, when taking into account death as a competing event, was 11% in high officials, 12% in intermediate non-manual employees, 14% in assistant non-manual employees, 14% in skilled workers, and 16% in unskilled and semi-skilled workers. Men with unskilled and semi-skilled manual occupations had a significantly higher risk of diabetes than high officials (reference) after adjustment for age, BMI, hypertension, smoking and physical activity (SHR 1.39, 95% CI 1.08-1.78). Additional adjustment for self-reported psychological stress did not attenuate the results. CONCLUSIONS: A low occupational class suggests a greater risk of Type 2 diabetes, independently of conventional risk factors and psychological stress.

Perceived stress and incidence of Type 2 diabetes: a 35-year follow-up study of middle-aged Swedish men.

AIM: To explore incident cases of diagnosed diabetes over 35 years of follow-up in relation to self-perceived stress at baseline. METHODS: This was a population-based random sample of 7251 men derived from the Primary Prevention Trial Study, aged 47-56 years at baseline and without prior history of diabetes, coronary heart disease and stroke. Incident diabetes was identified from hospital discharge and death registries as principal or secondary diagnosis. Cox proportional hazards regression was used to evaluate the potential association between stress and diabetes. RESULTS: During a 35-year follow-up, a total of 899 men were identified with diabetes. The crude incidence was 5.2 per 1000 persons-years. At baseline, 15.5% men reported permanent stress related to conditions at work or home. After adjusting for age and competing risk of death, the estimated 35-year conditional probability of diabetes in men with permanent stress was 42.6%, compared with 31.0% for those with periodic stress and 31.2% with no stress. In age-adjusted Cox regression analysis, men with permanent stress had a higher risk of diabetes [hazard ratio 1.52 (95% CI 1.26-1.82)] compared with men with no (referent) or periodic stress [hazard ratio 1.09 (95% CI 0.94-1.27)]. The association between stress and diabetes was slightly attenuated but remained significant after adjustment for age, socio-economic status, physical inactivity, BMI, systolic blood pressure and use of anti-hypertensive medication [hazard ratio 1.45 (95% CI 1.20-1.75)]. When examining principal diagnosis of diabetes cases separately from secondary diagnoses cases, the excess risk of diabetes associated with permanent stress remained significant both in age (only) and multivariable adjusted models. CONCLUSION: Self-perceived permanent stress is an important long-term predictor of diagnosed diabetes, independently of socio-economic status, BMI and other conventional Type 2 diabetes risk factors.

Factors associated with reaching 90 years of age: a study of men born in 1913 in Gothenburg, Sweden.

OBJECTIVES: Increasing numbers of people reach old age. We wanted to identify variables of importance for reaching 90 years old and determine how the predictive ability of these variables might change over time. SETTING AND SUBJECTS: All men in the city of Gothenburg born in 1913 on dates divisible by 3, which is on the 3rd, 6th, 9th etc., were included in the study. Thus, 973 men were invited, and 855 were examined in 1963 at age 50. Further examinations were made at age 54, 60 and 67. Anthropometric data, lifestyle and parental factors, blood pressure, lung function, X-ray of heart and lungs and maximum work performance were recorded. The area under the receiver operating characteristic curve was used to analyse the predictive capacity of a variable. RESULTS: A total of 111 men (13%) reached 90 years of age, men who reached 90 years were more likely at age 50 to be nonsmokers, consume less coffee, have higher socio-economic status and have low serum cholesterol levels than those who did not reach this age; however, at age 50 or 62, parents' survival was of no prognostic importance. Variables of greatest importance at higher ages were low blood pressure and measures related to good cardiorespiratory function. In multivariable analysis, including all examinations, being a nonsmoker, consuming small amounts of coffee, having high housing costs at age 50, good maximum working capacity and low serum cholesterol were related to a better chance of survival to age 90. CONCLUSIONS: Low levels of cardiovascular risk factors, high socio-economic status and good functional capacity, irrespective of parents' survival, characterize men destined to reach the age of 90.

High serum total cholesterol is a long-term cause of osteoporotic fracture.

SUMMARY: Risk factors for osteoporotic fractures were evaluated in 1,396 men and women for a period of 20 years. Serum total cholesterol was found to be an independent osteoporotic fracture risk factor whose predictive power improves with time. INTRODUCTION: The purpose of this study was to evaluate long-term risk factors for osteoporotic fracture. METHODS: A population random sample of men and women aged 25-64 years (the Gothenburg WHO MONICA project, N = 1,396, 53% women) was studied prospectively. The 1985 baseline examination recorded physical activity at work and during leisure time, psychological stress, smoking habits, coffee consumption, BMI, waist/hip ratio, blood pressure, total, HDL and LDL cholesterol, triglycerides, and fibrinogen. Osteoporotic fractures over a period of 20 years were retrieved from the Gothenburg hospital registers. Poisson regression was used to analyze the predictive power for osteoporotic fracture of each risk factor. RESULTS: A total number of 258 osteoporotic fractures occurred in 143 participants (10.2%). As expected, we found that previous fracture, smoking, coffee consumption, and lower BMI each increase the risk for osteoporotic fracture independently of age and sex. More unexpectedly, we found that the gradient of risk of serum total cholesterol to predict osteoporotic fracture significantly increases over time (p = 0.0377). CONCLUSIONS: Serum total cholesterol is an independent osteoporotic fracture risk factor whose predictive power improves with time. High serum total cholesterol is a long-term cause of osteoporotic fracture.

Obesity, smoking and secular trends in cardiovascular risk factors in middle-aged women: data from population studies in Göteborg from 1980 to 2003.

BACKGROUND: To study the trends in cardiovascular risk factors in middle-aged city-dwelling Swedish women from 1980 to 2003. METHODS: Using cross-sectional population-based surveys, five random population samples of a total of 1915 women aged between 45 and 54 years, participating in the BEDA study in 1980, WHO MONICA studies in 1985, 1990 and 1995, and a study of 50-year-old women in 2003 were measured for the following parameters: anthropometry, serum cholesterol and triglyceride levels, smoking habits, blood pressure, physical activity and stress. RESULTS: Over almost 25 years, middle-aged women gained on average 4.4 kg in weight, with a net increase in body mass index (BMI) from 24.7 to 25.6 kg m⁻². The proportion of participants classified as obese (≥30 kg m⁻²) increased by 50% from 10.4% to 15.1%. Women who were smokers in 2003 did not have lower BMI values than nonsmokers. Mean serum cholesterol concentrations decreased markedly, whereas smoking habits did not significantly change. The prevalence of hypertension decreased by 8%, whereas that of diabetes remained stable at around 2%. Optimal risk factor status - no smoking, normotension and serum cholesterol <5 mmol l⁻¹ - was present in less than one in six women in 2003, and similar across BMI categories. CONCLUSION: The favourable decline in cholesterol levels and hypertension and the increase in leisure time physical activity were offset by an increase in obesity, triglyceride levels and experience of stress, with only a minority of participants (less than one in six) having an optimal level of risk factors with respect to smoking, serum cholesterol and hypertension in 2003. This applied also to overweight and obese women. In earlier cohorts, subjects with low BMI values were more often smokers, whereas the opposite is observed in recent cohorts. Thus, women who smoke no longer have the advantage of lower weight.

Male risk factors for hip fracture-a 30-year follow-up study in 7,495 men.

SUMMARY: Risk factors for hip fracture were studied in 7,495 randomly selected men during 30 years; 451 men had a hip fracture. High degree of leisure-time, but not work-related, physical activity, high occupational class, and high body mass index (BMI) protected against hip fracture. Smoking, tall stature, interim stroke, and dementia increased the risk. PURPOSE: The purpose was to prospectively study risk factors for hip fracture in men. METHODS: We studied midlife determinants of future hip fractures in 7,495 randomly selected men aged 46-56 years in Gothenburg, Sweden. The subjects were investigated in 1970-1973 and followed for over 30 years. Questionnaires were used regarding lifestyle factors, psychological stress, occupational class, and previous myocardial infarction, stroke, and diabetes mellitus. Alcohol problems were assessed with the aid of registers. Using the Swedish hospital discharge register, data were collected on intercurrent stroke and dementia diagnoses and on first hip fractures (X-ray-verified). RESULTS: Four hundred fifty-one men (6%) had a hip fracture. Age, tall stature, low occupational class, tobacco smoking, alcoholic intemperance, and interim stroke or dementia were independently associated with the risk of hip fracture. There were inverse associations with leisure-time physical activity, BMI, and coffee consumption. The gradient of risk for one standard deviation of multivariable risk decreased with time since measurement yet was a good alternative to dual energy X-ray absorptiometry measurements. CONCLUSIONS: High degree of leisure-time physical activity, high occupational class, and high BMI protected against hip fracture. However, work-related physical activity was not protective. Smoking, tall stature, and interim stroke or dementia increased the risk.

Obesity and trends in cardiovascular risk factors over 40 years in Swedish men aged 50.

OBJECTIVE: To study trends over 40 years in cardiovascular risk factors in normal weight, overweight and obese men, all aged 50 when examined. Design. Cross-sectional studies of five successive cohorts of men aged 50. SETTING: City of Göteborg, Sweden. SUBJECTS: Random population samples of altogether 3251 urban Swedish men born in 1913, 1923, 1933, 1943 and 1953. MAIN OUTCOME MEASURES: Anthropometry, cardiovascular risk factors, rates of nonsmoking, normotension and serum cholesterol <5 mmol L(-1) over four decades. RESULTS: Over 40 years, there was a net increase in body mass index (BMI) from 24.8 (SD = 3.2) to 26.4 (3.7) kg m(-2) (P < 0.0001), with an increase in the prevalence of obesity (BMI >or= 30 kg m(-2)) from 6.0% in 1963 to 13.8% in 2003. Favourable trends with respect to smoking, blood pressure and serum cholesterol were observed similarly amongst normal weight, overweight and obese men. In 1963, 24% of obese men were normotensive compared to 45% in 2003, and 6% had serum cholesterol <5 mmol L(-1) compared to 34% in 2003. Compared with obese men in 1963, men who were obese in 2003 had an odds ratio (OR) of 3.39 being a nonsmoker [95% confidence interval (CI): 1.56 to 7.36], 2.67 of being normotensive (1.23 to 5.83) and having serum cholesterol <5 mmol L(-1) of 8.30 (2.37 to 29.0). However, optimal risk factor status - no smoking, normotension and total serum cholesterol <5 mmol L(-1)- was still present in less than one in six men in 2003, similar across BMI categories. CONCLUSIONS: Obese Swedish men who are now in their fifties have much lower levels of other risk factors compared with obese men 40 years ago. This could contribute to explain why coronary heart disease death rates still are falling despite increasing rates of obesity.

Secular changes in cardiovascular risk factors and attack rate of myocardial infarction among men aged 50 in Gothenburg, Sweden. Accurate prediction using risk models.

AIMS: Coronary risk factor changes were related to attack rate of acute myocardial infarction (AMI). METHODS AND RESULTS: Cross-sectional population samples of 50-year-old men were examined every 10th year from 1963 to 2003. Attack rates of AMI were recorded from 1975 to 2004. Prevalence of smoking decreased from 56% in 1963 to 22% in 2003. Leisure time physical activity decreased (n.s.), while psychological stress remained the same. Diabetes prevalence increased from 3.6% to 6.6%. Body mass index (BMI) increased from 24.8 to 26.4 kg m(-2). Blood pressures decreased from 138.2/90.6 to 134.7/84.9 mmHg (P = 0.00001). Serum total cholesterol decreased from 6.42 to 5.50 mmol L(-1) (P = 0.0001), but serum triglycerides increased from 1.26 to 1.71 mmol L(-1) (P = 0.0001). The multivariable risk according to total cholesterol, blood pressure and smoking for AMI decreased from the set value 1.0 in 1963 to 0.418. From 1975-1979 to 2000-2004 attack rates for AMI for the age groups 35-44, 45-54 and 55-64 declined to 45%, 46% and 45%, respectively. The 28-day case fatality declined from 30%, 38% and 46% to 12%, 16% and 20%. CONCLUSION: The more than 50% decline in attack rate of AMI during 30 years was comparable with the decline in risk factors.

The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913.

In a prospective study of risk factors for ischemic heart disease, 792 54-yr-old men selected by year of birth (1913) and residence in Göteborg, Sweden, agreed to attend for questioning and a number of anthropometric and other measurements in 1967. Thirteen and one-half years later, these baseline findings were reviewed in relation to the number of men who had subsequently developed diabetes mellitus. This analysis focused on the importance of abdominal adipose tissue distribution, measured as the waist-to-hip circumference ratio, as a predictor for development of diabetes. Even when the confounding effect of body mass index, as a measure of the total body fat mass, was accounted for, the waist-to-hip ratio was positively and significantly associated with the risk for diabetes. These results from a prospective study strongly support previous cross-sectional findings indicating that not only the degree of obesity but also the localization of fat is a risk factor for diabetes.

Long-term prognosis after myocardial infarction in men with diabetes.

Men (1306) who survived a first myocardial infarction (MI) were studied. The mean follow-up time was 6.5 yr, and at the end of the follow-up period survival status was known for all patients. By the time of the MI the prevalence of diabetes was 5.6%. Patients with and without diabetes were compared. There were no differences in the estimated primary or secondary risk. The cumulative survival rate 1, 2, and 5 yr after the MI was 82, 78, and 58% among the diabetic subjects compared with 94, 92, and 82% among the nondiabetic subjects (P less than 0.001). The difference remained even after allowance for age and estimated secondary risk in a multivariate regression analysis. There were no differences in mortality rates among patients with type I diabetes compared with type II diabetes, nor among patients treated with diet alone, sulfonylurea, or insulin, but the numbers were small. The cumulative rate of reinfarctions after 1, 2, and 5 yr was 18, 28, and 46% in diabetic subjects and 12, 17, and 27% in nondiabetic subjects (P = 0.004). A history of diabetes was an independent secondary risk factor among male survivors of a first MI with respect to deaths and reinfarctions.

Smoking cessation and arrhythmic death: the CAST experience. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators.

OBJECTIVES: This study was performed to assess the effect of cigarette smoking cessation on overall mortality and the incidence of arrhythmic death in the population of the Cardiac Arrhythmia Suppression Trial (CAST). BACKGROUND: Cigarette smoking is a known risk factor for sudden cardiac death. Some of the adverse effects of smoking have been shown to dissipate with smoking cessation, but the time frame over which these changes occur and the population that stands to benefit have not been well delineated. CAST was a multicenter double-blind placebo-controlled study to determine whether suppression of ventricular ectopic activity by means of antiarrhythmic drugs in patients with left ventricular dysfunction after acute myocardial infarction would reduce the incidence of arrhythmic death. METHODS: Of 2,752 patients randomized to blinded therapy, 1,026 were smoking at the time of their baseline examination and completed a 4-month follow-up visit. Of these, 517 stopped smoking by the time of this visit ("quitters") and 509 continued to smoke ("smokers"). RESULTS: Over a mean follow-up period of slightly < 16 months, there were 17 arrhythmic deaths and 32 total deaths among the quitters versus 30 and 45, respectively, among the smokers; these differences were of marginal statistical significance. Most of the fatal events occurred in a group at high risk of ongoing ischemia: the 558 patients who did not have thrombolysis or undergo revascularization after their qualifying myocardial infarction. In this high risk cohort, smoking cessation greatly reduced the incidence of arrhythmic death and was associated with a statistically significant benefit in survival. CONCLUSIONS: Smoking cessation was accompanied by a marked reduction in arrhythmic death and overall mortality that achieved statistical significance in a high risk cohort. These data imply that smoking cessation is important in risk factor reduction in patients with advanced ischemic heart disease.

Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: "the study of men born in 1913".

BACKGROUND: Risk factors for deep vein thrombosis and pulmonary embolism are mostly derived from case-control studies of hospitalized patients, and there are few long-term population-based studies. OBJECTIVE: To study the long-term risk factors for deep vein thrombosis and pulmonary embolism among middle-aged men. DESIGN: A prospective cohort study. SETTING: General community, "The Study of Men Born in 1913." SUBJECTS: A random population sample of 855 men, all aged 50 years at baseline. MAIN OUTCOME MEASURES: Eight-hundred fifty-five men participated in a screening examination in 1963 at the age of 50 years, and 792 of these men were reexamined in 1967 at the age of 54. All the men were followed up with periodic examinations until the age of 80. Objective methods were used to ascertain a diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Waist circumference (P=.004) and smoking (P = .02) predicted a venous thromboembolic event in multivariate survival analysis. Men in the highest decile of waist circumference (> or =100 cm) had an adjusted relative risk of 3.92 (95% confidence interval, 2.10-7.29; P<.001) compared with men with a waist circumference of less than 100 cm. For men who smoked 15 g of tobacco (15 cigarettes) a day or more, the adjusted relative risk was 2.82 (95% confidence interval, 1.30-6.13; P= .009) compared with nonsmokers. CONCLUSIONS: Smoking and abdominal obesity were independent risk factors for venous thromboembolic events during follow-up. In addition to the prevention of smoking and obesity, a more aggressive strategy regarding the use of prophylactic agents among smokers and obese patients, in various risk situations, may be justified.

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.

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Diabetes and long-term risk of mortality from coronary and other causes in middle-aged Swedish men. A general population study.

OBJECTIVE: To assess the relation between cardiovascular risk factors and long-term cause-specific mortality risk in middle-aged diabetic men, compared with men without diabetes. RESEARCH DESIGN AND METHODS: This prospective study analyzes a large random population sample of men over a follow-up of 16 years. At baseline in 1974-1977, 249 men with diabetes and 6,851 men without diabetes, all aged 51-59 years, were identified. There were 2,126 deaths, 724 of which were due to coronary heart disease (CHD) and 1,001 deaths were due to any cardiovascular disease (CVD) cause. RESULTS: After adjustment for age, serum cholesterol, systolic blood pressure, smoking, BMI, and coronary disease at baseline, the relative risk of dying from any cause was 2.50 (95% CI, 2.11-2.95) in men with diabetes, compared with nondiabetic men, and 2.87 (2.31-3.57) for cardiovascular death. Men with diabetes had no significant excessive risk of dying from cancer or violent causes, but the relative risk of dying from any other noncardiovascular cause was 3.69 (2.55-5.34). Most of these deaths were due to diabetes and its complications. Hypercholesterolemia, smoking, and elevated systolic blood pressure predicted both coronary and all-cause mortality in diabetic as well as in nondiabetic men. Men with diabetes and serum cholesterol > 7.2 mmol/l had a risk of dying from coronary disease of 45.3 and from any cause of 76.1 per 1,000 observation-years. In men with diabetes, the relative risk of dying associated with serum cholesterol > 7.2 mmol/l, as compared with < 5.2 mmol/l, was 1.78 (95% CI, 1.05-3.02). The corresponding risk for nondiabetic men was 1.23 (1.04-1.46), and there was a statistically significant interaction between serum cholesterol and diabetes (P = 0.004). CONCLUSIONS: In men with diabetes, hypercholesterolemia, smoking, and hypertension predict coronary mortality risk, as well as mortality risk from all causes. Men with both diabetes and hypercholesterolemia have severely compromised survival and should be targeted for intervention aimed at lowering their lipid levels.

Risks of untreated hypertension. A discussion.

There is a strong and graded association between blood pressure and the incidence of major coronary heart disease manifestations, congestive heart failure, stroke, and total mortality. The risk of any of these manifestations is also modified by other risk factors. Tobacco smoking affects the risk for all of the previously mentioned end points. Generally, lipid disturbances are only important predictors of coronary heart disease and total mortality. Several facts indicate that elevated blood pressure is causally related to the end points. There are, however, positive relations between blood pressure levels and heart rate, serum cholesterol level, body mass index, and, according to some studies, glucose intolerance. Some more basic abnormality may be responsible for the blood pressure increase and the increases in these other factors. Hypothetically, this abnormality may be more fundamentally related to some of the end points than is hypertension itself. If that is the case, then the type of antihypertensive treatment may be of decisive importance. Different end points may be affected differently by antihypertensive drugs, a factor that may be essential in the choice of drug treatment. Proper management of other risk factors is also essential in the prevention of cardiovascular disease.

The main end points in human hypertension.

Prospective data from Western populations show a fairly steady increase in the incidence of total mortality as well as of myocardial infarction (MI) and sudden coronary death (SD) with increasing blood pressure levels. In the age groups up to 70 years, stroke is much less common than MI and SD at virtually all blood pressure levels, but for older men and also for somewhat younger women, stroke is as common as MI and SD at the highest blood pressure levels. The incidence of MI and SD is strongly dependent on serum lipid abnormalities and smoking habits, whereas stroke appears to depend very little on lipid levels and in only a few studies appears related to smoking habits. Thus, the effect of blood pressure is appreciably modified by the presence of some other abnormalities that are believed to enhance coronary arteriosclerosis. There are major differences between populations with respect to the incidence of MI, SD, and stroke. MI mortality and SD have, for example, been very high in the United States, whereas stroke mortality has been low. In Japan, on the other hand, stroke mortality has been high and MI mortality and SD have been low. Sweden has occupied an intermediate position with respect to MI mortality and SD, which have been increasing slightly while they have been decreasing in the United States, whereas stroke mortality in Sweden and in the other Scandinavian countries has been very low and is even showing a slight decrease. Both prospective epidemiologic studies and intervention trials indicate some influence of blood pressure on noncardiovascular mortality, such as that from cancer.

Cardiac malformations and hypertension, but not metabolic risk factors, are common in Turner syndrome.

Turner syndrome (TS) is caused by an X chromosome aberration and is characterized by endogenous estrogen deficiency secondary to ovarian dysgenesis and short stature. Our aim was to study the prevalence of cardiovascular malformations and cardiovascular risk factors (blood pressure, blood lipids and glucose, coagulation factors, social factors, smoking habits) in adults with Turner syndrome in comparison with a female random population sample. One hundred women with Turner syndrome (aged 16-71 yr) underwent physical examination, echocardiography, electrocardiography, and blood sampling. Seventy-one of them were matched for age [mean age, 33.7 +/- 11 yr (range, 25-64)] with a random population sample (n = 213) of women [mean age, 34.8 +/- 9 yr (range, 25-64)] from the World Health Organization's Monitoring of Trends and Determinants in Cardiovascular Diseases Project, Göteborg. Six percent of Turner syndrome women were smokers compared with 25% in the population (P < 0.001). Turner syndrome women were relatively heavier and had a lower degree of leisure time physical activity than controls (P < 0.001). Diabetes and treatment for hypertension were present in 3 and 22% among Turner syndrome women vs. 2% (not significant) and 3% (P < 0.001) in controls, respectively. Cardiovascular malformations were found among 17% in Turner syndrome women (45,X dominated) vs. 0.5% in controls (P < 0.001). Systolic but not diastolic blood pressure was higher in Turner syndrome women. No differences were seen in serum total cholesterol, high- or low-density lipoprotein cholesterol, triglycerides, lipoprotein (a), or plasma fibrinogen concentrations between patients and controls. Diabetes or hypertension was not related to karyotype. In conclusion, congenital cardiovascular malformations were frequent. Most cardiovascular risk factors (glucose and lipid levels, fibrinogen, smoking habits) were not increased, but hypertension was more common in Turner syndrome women.

Type of obesity and blood pressure.

To explore the relationship between blood pressure on the one hand and body composition variables and fat cell size and number on the other, these factors were determined in a population sample (n = 120) of 49-year-old men with blood pressure (BP) ranging from very low to very high. BP increased linearly with body weight throughout the entire BP range, while body fat and fat cell size increased with increasing BP in the nonhypertensive but not in the hypertensive BP range. Body cell mass and fat cell number were unrelated to BP. Fat cell size (but not fat cell number) was positively correlated with most variables of glucose metabolism. It can be concluded that in normal men: the previously well-established relationship between body weight and BP is explained by an association between body fat and BP; BP is positively correlated with increased fat cell size, indicating hypertrophic obesity, while BP is unrelated to fat cell number; and increased fat cell size is associated with impaired glucose tolerance and hyperinsulinemia. The results point to the possibility that hypertrophic obesity and essential hypertension may be related to each other via common pathogenetic mechanisms.

Diastolic function of the heart in untreated primary hypertension.

To study left ventricular (LV) diastolic function of the heart in relation to blood pressure (BP) and other signs of hypertensive cardiac and peripheral vascular changes, isovolumic relaxation time and early diastolic filling were determined in four BP groups of untreated 49-year-old men: normotensive subjects (n = 20), men with borderline hypertension (n = 30), mild hypertension (n = 45), and moderate to severe hypertension (n = 24). Isovolumic relaxation time, measured as the distance between aortic closure (A2, phonocardiography) and mitral valve opening (echocardiography), and early diastolic filling, measured as the distance between mitral valve opening and the O point of the apexcardiogram, tended to increase with BP level, and the total interval from aortic closure to the O point (A2O interval) was significantly prolonged in the two groups with mild and moderate to severe hypertension. A prolonged A2O interval (greater than or equal to 117% of expected value at observed heart rate) was seen in several hypertensives, who had no obvious increase in LV wall thickness on M mode echocardiography. This suggests that a prolonged LV relaxation time may be an early sign of cardiac involvement in primary hypertension. In the group with moderate to severe hypertension, an increase in LV wall thickness was seen together with an increase in resistance at maximal dilation in the calf. This supports the theory that when changes in cardiac structure develop they occur in parallel with structural changes also in the periphery.