Lennart Welin

Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913.

In a prospective study of risk factors for ischaemic heart disease 792 54 year old men selected by year of birth (1913) and residence in Gothenburg agreed to attend for questioning and a battery of anthropometric and other measurements in 1967. Thirteen years later these baseline findings were reviewed in relation to the numbers of men who had subsequently suffered a stroke, ischaemic heart disease, or death from all causes. Neither quintiles nor deciles of initial indices of obesity (body mass index, sum of three skinfold thickness measurements, waist or hip circumference) showed a significant correlation with any of the three end points studied. Statistically significant associations were, however, found between the waist to hip circumference ratio and the occurrence of stroke (p = 0.002) and ischaemic heart disease (p = 0.04). When the confounding effect of body mass index or the sum of three skinfold thicknesses was accounted for the waist to hip circumference ratio was significantly associated with all three end points. This ratio, however, was not an independent long term predictor of these end points when smoking, systolic blood pressure, and serum cholesterol concentration were taken into account. These results indicate that in middle aged men the distribution of fat deposits may be a better predictor of cardiovascular disease and death than the degree of adiposity.

Fibrinogen as a Risk Factor for Stroke and Myocardial Infarction

To study the possible risk factors for cardiovascular disease, we collected data on plasma levels of coagulation factors, blood pressure, serum cholesterol, and smoking in a random sample of 792 men 54 years of age. During 13.5 years of follow-up, myocardial infarction occurred in 92 men, stroke in 37, and death from causes other than myocardial infarction or stroke in 60. The blood pressure, degree of smoking, serum cholesterol, and fibrinogen level measured at the base-line examination proved to be significant risk factors for infarction by univariate analyses during follow-up, and blood pressure and fibrinogen were risk factors for stroke. Fibrinogen and smoking were strongly related to each other. The relation between fibrinogen and infarction, and between fibrinogen and stroke, became weaker when blood pressure, serum cholesterol, and smoking habits were taken into account, but was still significant for stroke. Although causality cannot be inferred from these data, it is possible that the fibrinogen level plays an important part in the development of stroke and myocardial infarction.

Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): Effects on mortality at 1 year

OBJECTIVES We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. BACKGROUND Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. METHODS A total of 620 patients were studied: 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy. RESULTS The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6 +/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the 1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046]; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). CONCLUSIONS Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.

Analysis of Risk Factors for Stroke in a Cohort of Men Born in 1913

We analyzed parental death from stroke and other potential risk factors in relation to the incidence of stroke among 789 men, all 54 years old at the base-line examination. During 18.5 years of follow-up, 57 men (7.2 percent) had strokes. In univariate analyses, the following characteristics correlated significantly with the incidence of stroke: increased systolic (P = 0.004) and diastolic blood pressure (P = 0.0001), larger waist circumference (P = 0.007), higher waist:hip ratio (P = 0.0004), increased plasma fibrinogen level (P = 0.01), and lower vital capacity (P = 0.03). In addition, men whose mothers had died of stroke had a threefold increase in their incidence of stroke as compared with men without such a maternal history (P = 0.0005). Potential risk factors for stroke that were not confirmed were body-mass index, serum cholesterol level, hematocrit, blood glucose level, smoking, coronary heart disease, electrocardiographic signs of left ventricular hypertrophy, and a paternal history of death from stroke. In multivariate analyses, increased blood pressure, abdominal obesity, increased plasma fibrinogen level, and maternal history still correlated significantly with the risk of stroke. A maternal history of stroke should probably be added to the list of risk factors for stroke among middle-aged men.

Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study.

OBJECTIVE--To investigate the effect of cardiovascular risk factors on coronary heart disease and all cause mortality in middle aged diabetic men. DESIGN--Prospective population study based on data collected from second screening (from 1974 to 1977) in the multifactor primary prevention trial and follow up until March 1983. SETTING--Gothenburg, Sweden. SUBJECTS--6897 Men aged 51 to 59, of whom 232 were self reported diabetics and 6665 were non-diabetic; none had a history of myocardial infarction. MAIN OUTCOME MEASURES--Incidences of coronary heart disease and mortality from all causes. RESULTS--Diabetic men with a serum cholesterol concentration greater than 7.3 mmol/l had a significantly higher incidence of coronary heart disease during follow up than those with a concentration less than or equal to 5.5 mmol/l (28.3% v 5.4%; p = 0.020); corresponding figures for non-diabetic men were 9.4% and 2.4% respectively. In multivariate logistic regression analyses serum cholesterol concentration and smoking habit were independent predictors of coronary heart disease (odds ratio serum cholesterol concentration 6.1 (95% confidence interval 2.1 to 17.6) current smoking 2.9 (1.1 to 7.5)) and of all cause mortality (3.2 (1.3 to 7.9), 3.0 (1.4 to 6.7) respectively) in diabetic men whereas systolic blood pressure, body mass index, family history, marital state, and alcohol abuse were not. Low occupational class was an independent predictor of mortality (2.4 (1.01 to 5.5)), but not of coronary heart disease, in diabetic men. CONCLUSIONS--Middle aged diabetic men with hypercholesterolaemia are at very high risk of developing coronary heart disease and of dying prematurely. Lowering serum cholesterol concentration in such subjects seems to be warranted.

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Social influences and cardiovascular risk factors as determinants of plasma fibrinogen concentration in a general population sample of middle aged men.

OBJECTIVE--To analyse the relation between fibrinogen concentration and social class and other social factors found to be related to mortality. The results regarding cardiovascular disease are unpublished, as yet. DESIGN--Cross sectional population study. SETTING--City of Gothenburg, Sweden. SUBJECTS--639 Men from a population sample of 1016 men aged 50 in 1983. They were all employed and had no history of myocardial infarction or stroke. Fibrinogen values were available for all of them. MAIN OUTCOME MEASURE--Fibrinogen concentration in relation to socioeconomic state according to occupation, and other social influences determined as number of people in the household and scores of social activities and activities in and outside the house. RESULTS--Men with low scores for activities at home had a mean plasma fibrinogen concentration of 3.34 g/l (95% confidence interval 3.21 to 3.47), whereas those with an intermediate score had a mean concentration of 3.16 (3.00 to 3.32) g/l and those with a high score 3.02 (2.95 to 3.10) g/l. Similar inverse relations were noted for the two other activity scores and for occupational class (class 1 being unskilled and semiskilled workers and class 5 professionals and executives) and the number of people in the household. Smoking exerted a strong influence on fibrinogen concentration, the relations between fibrinogen concentration and social factors being evident only in non-smokers. The mean difference in fibrinogen value between the non-smokers with the lowest activity scores at home and those with the highest scores was 0.36 (0.19 to 0.54) g/l, and similar differences were seen for the two other activity scores. Multiple regression analyses showed smoking, body mass index, the sum of all activities (inverse relation), and diabetes to be independently associated with fibrinogen value, whereas occupational class (p = 0.81) and the number of people in the household (p = 0.09) were not. CONCLUSIONS--Psychosocial influences seem to influence the coagulation system in the body in a way that is associated with cardiovascular disease and premature death.

Association of Cardiometabolic Multimorbidity With Mortality The Emerging Risk Factors Collaboration

IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Obesity, adipose tissue distribution and health in men—The study of men born in 1913

Recent studies suggest that cardiovascular disease is associated with abdominal distribution of adipose tissue rather than obesity in terms of total body fat. A number of other variables, known to be associated with obesity, were therefore examined in a cohort of randomly selected middle-aged men in relation to abdominal distribution of adipose tissue, measured as the ratio of the circumferences of the waist and hips (WHR), as well as to degree of obesity, measured as body mass index (BMI). These variables included anthropometric variables, cardiovascular risk factors as well as socioeconomic factors and physical health. Increased WHR, independent of BMI, was negatively associated with height, and hip circumference. Positive associations were found with blood pressure, cholesterol, triglycerides, fibrinogen and smoking. In addition positive associations were found with low social class and social group, illness in terms of sick leave, frequent use of health facilities such as X-rays, as well as diseases such as peptic ulcer. In sharp contrast to this, BMI, independent of WHR, was not associated with physical health variables or social class. Generalized obesity seemed to be associated with good health in the variables measured. There were positive associations to various anthropometric variables, including lean body mass. High BMI was also associated with elevated blood pressure and triglycerides. Several of the indicators of poor health traditionally associated with obesity thus do not seem to be characteristic for obesity in middle-aged men selected at random from the population but rather for an abdominal fat distribution, independent of obesity.

Metabolic disturbances in hypertension: results from the population study ‘ Men born in 1913’

A clustering of metabolic disturbances has been indicated in hypertension. The distribution of such factors was assessed among hypertensives and normotensives in a general population sample of 644 men aged 67 years. Fasting serum insulin, glucose and triglyceride levels were measured. In this study hypertension was defined as DBP ≥ 95 mmHg or present use of antihypertensives. Impaired glucose tolerance (IGT) or diabetes mellitus, hyperinsulinaemia (≥ 20 mU l−1) and hypertriglyceridaemia (≥ 2.3 mmol l−1) were defined as metabolic disturbances. When all these disturbances were present simultaneously a complete ‘metabolic syndrome’ was considered to be present. Hypertension was found in 185 (29%) men, IGT in 15%, diabetes mellitus in 11%, hyperinsulinaemia in 18% and hypertriglyceridaemia in 19%. Among hypertensives, 11 (6%) men had a ‘metabolic syndrome’, compared to 12 (3%) men in the normotensive group (P = 0.039). At least one metabolic disturbance was present in 109 (59%) of the hypertensive men, and in 173 (38%) of the normotensive men (P < 0.001). The prevalence rates of metabolic disturbances did not differ significantly between lean (BMI < 26 kg m−2) and obese (BMI ≥ 26 kg m−2) hypertensives. Only hypertriglyceridaemia was more frequent in obese than in lean hypertensives (20% vs. 37%, P = 0.015). The ‘metabolic syndrome’ was found in 6% of all hypertensives, which was twice as common as in the normotensive population. The ‘metabolic syndrome’ was uncommon in both lean and obese hypertensives (5% vs. 7%, NS). These findings indicate that hypertension and metabolic disturbances may have a common underlying cause, at least in some individuals.