Leif Lapidus

Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenburg, Sweden.

A longitudinal population study of 1462 women aged 38-60 was carried out in Gothenburg, Sweden, in 1968-9. In univariate analysis the ratio of waist to hip circumference showed a significant positive association with the 12 year incidence of myocardial infarction, angina pectoris, stroke, and death. The association with incidence of myocardial infarction remained in multivariate analysis and was independent of age, body mass index, smoking habit, serum cholesterol concentration, serum triglyceride concentration, and systolic blood pressure. The relation between the ratio of waist to hip circumference and the end points of myocardial infarction, angina pectoris, stroke, and death was stronger than for any other anthropometric variable studied.

Polycystic ovary syndrome and risk for myocardial infarction: Evaluated from a risk factor model based on a prospective population study of women

In order to estimate whether women with polycystic ovary syndrome (PCOS) have an increased risk of developing myocardial infdrction, a risk factor model was applied on 33 women with PCOS and 132 age matched referents.

Low Sex-Hormone-Binding Globulin Concentration as Independent Risk Factor for Development of NIDDM: 12-Yr Follow-Up of Population Study of Women in Gothenburg, Sweden

Serum sex-hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were evaluated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM), myocardial infarction, stroke, and premature death in a prospective study of 1462 randomly selected women, aged 38–60 yr, over 12 yr of observation. In multivariate analysis, taking only age into consideration as a confounding factor, low initial concentration of SHBG was significantly correlated to the incidence of NIDDM and stroke, and high initial concentration of CBG was correlated to the incidence of NIDDM. There were also significant correlations between SHBG and CBG concentrations on one hand and possible risk factors for the end points studied, such as serum triglycerides, serum cholesterol, fasting blood glucose, body mass, body mass index, waist/hip ratio, smoking habits, and systolic blood pressure, on the other. When these possible confounders, in addition to age, were taken into consideration in multivariate analyses, only the inverse significant correlation between SHBG and NIDDM remained. The increased incidence of diabetes was confined to the lowest quintile of SHBG values, where it was 5-fold higher than in the remaining group. This incidence was further increased to 8- and 11-fold in the lowest 10 and 5% of the values, respectively. We conclude that SHBG is a uniquely strong independent risk factor for the development of NIDDM in women.

Symptoms by Age and Sex: The Population Studies of Men and Women in Gothenburg, Sweden

Symptoms by age and sex were studied in two population studies from Gothenburg, Sweden. In general, men and women showed the same age-related pattern. The prevalence of the following symptoms increased with age--sleeping disturbances, pain in the joints, pain in the legs, breathlessness, and impaired hearing. Six symptoms decreased with age--general fatigue, abdominal pain, nausea, diarrhoea, cough, and headache. A group of symptoms showed a curvilinear shape with a peak at the age of 50. In general, women presented more symptoms than men. This was especially true for symptoms of depression and tension. A possible explanation is that women are more attentive to their internal state. A more probable explanation, supported by our study, is that the mental symptoms are related to the womans situation in life with double work (responsible for both work and family).

Screening for iron deficiency: an analysis based on bone‐marrow examinations and serum ferritin determinations in a population sample of women

Summary Efficacy of different methods in screening for iron deficiency was re‐examined in a randomly selected sample of 38‐year‐old women (n= 203) with known iron status based on absence/presence of stainable iron in bone‐marrow smears. The study was made in 1968–69. Serum ferritin (SF) was determined in 1978 in frozen sera using the Kamco IRMA and, in 1992, samples were re‐analysed using a RIA calibrated with the International Standard 80/602 for SF determination. The effect of storage on SF was calculated from a previously established relationship (courtesy of Dr Mark Worwood. Cardiff) between the results obtained with the Ramco assay and assays calibrated with IS 80/602. The distributions in iron replete and iron deficient women showed less overlap (diagnostic efficiency 91%) for SF than for other haematological parameters. The best discrimination was obtained at SF<16 μg/l (specificity 98%: sensitivity 75%). Absence of iron stores was associated with signs of an iron deficient erythropoiesis. starting already at SF 25–40 μg/l. Use of multiple criteria to diagnose iron deficiency falsely reduces prevalence figures for iron deficiency.

Associations of serum lipid concentrations and obesity with mortality in women: 20 year follow up of participants in prospective population study in Gothenburg, Sweden.

OBJECTIVE--To examine association of different measures of serum lipid concentration and obesity with mortality in women. DESIGN--Prospective observational study initiated in 1968-9, follow up examination after 12 years, and follow up study based on death certificates after 20 years. SETTING--Gothenburg, Sweden. SUBJECTS--1462 randomly selected women aged 38-60 at start of study. MAIN OUTCOME MEASURES--Total mortality and death from myocardial infarction as predicted by serum cholesterol and triglyceride concentrations, body mass index, and ratio of circumference of waist to circumference of hips. RESULTS--170 women died during follow up, 26 from myocardial infarction. Serum triglyceride concentration and waist:hip ratio were significantly associated with both end points (relative risk of total mortality for highest quarter of triglyceride concentration v lower three quarters 1.86 (95% confidence interval 1.30 to 2.67); relative risk for waist:hip ratio 1.67 (1.18 to 2.36)). These associations remained after adjustment for background variables. Serum cholesterol concentration and body mass index were initially associated with death from myocardial infarction, but association was lost after adjustment for background variables. Serum triglyceride concentration and waist:hip ratio were independently predictive of both end points (logistic regression coefficient for total mortality for triglyceride 0.514 (SE 0.150), p = 0.0006; coefficient for waist:hip ratio 7.130 (1.92), p = 0.0002) whereas the other two risk factors were not (coefficient for total mortality for cholesterol concentration -0.102 (0.079), p = 0.20; coefficient for body mass index -0.051 (0.027), p = 0.05). CONCLUSIONS--Lipid risk profile appears to be different in men and women given that serum triglyceride concentration was an independent risk factor for mortality while serum cholesterol concentration was not. Consistent with previous observations in men, localisation of adipose tissue was more important than obesity per se as risk factor in women.

Obesity, adipose tissue distribution and health in women--results from a population study in Gothenburg, Sweden.

The associations between generalized obesity measured as body mass index (BMI), or adipose tissue distribution, measured as the waist/hip circumference ratio (WHR), on one hand, and a number of socioeconomic, somatic as well as psychologic and mental health variables on the other, were analysed in a population study of women (1462 participants, aged 38-60 years, participation rate 90.1%). The anthropometric measurements were adjusted for their influence on each other. BMI, but not WHR, was negatively associated with socioeconomic status and education. Increased WHR correlated to a number of somatic diseases from different organ systems, including diabetes mellitus, infectious respiratory and abdominal diseases. Even more striking were strong correlations to a number of variables indicating accident proneness as well as mental disorder, and increased use of antidepressants and tranquilizers. BMI and WHR were also associated to different personality profiles. Furthermore, the use of alcohol and smoking were positively correlated to the WHR. In contrast, most of these associations were not seen with the BMI--sometimes even negative correlations were found. Exceptions were, however, varicose veins, joint problems and surgery for gall bladder disease, which were positively correlated to BMI only. Blood pressure, plasma triglycerides and uric acid were positively correlated to both BMI and the WHR, plasma cholesterol, however, only to the WHR. Obesity (high BMI) and abdominal adipose tissue distribution (high WHR) clearly show differences in their associations to various health variables. It is hypothesized that an arousal syndrome might be a contributing factor to cause symptoms of psychological maladjustment, including psychosomatic disease. Hypothetically, in parallel, an accumulation of depot fat in the abdominal depot, might follow as a consequence of neuroendocrine dysregulation of endocrine secretions.

Fasting insulin in relation to subsequent blood pressure changes and hypertension in women.

The role of hyperinsulinemia in the development of hypertension is not well understood, particularly insofar as both conditions relate to obesity. The present analysis examines the hypothesis that hyperinsulinemia, independent of obesity, precedes hypertension and natural blood pressure increases in women. The subjects were 50-year-old women from a prospective population study in Gothenburg, Sweden. Fasting insulin levels were determined at baseline (1968-1969) and were evaluated in relation to subsequent hypertension. Blood pressures were measured at the initial physical examination and at the 6- and 12-year follow-up examinations. The first analysis presented here (n = 278) identified incident cases of hypertension during the 12-year follow-up period, whereas the second analysis (n = 219) examined continuous changes in blood pressure. In both analyses, degree, type, and changes in obesity were considered as possible confounding factors. High fasting insulin values were predictive of subsequent incidence of hypertension over the 12-year follow-up period. Subjects with insulin values above the 75th percentile experienced three times more hypertension than did those below the 25th percentile. There was also a significant association between insulin at baseline and increases in diastolic (but not systolic) blood pressure. The positive relations between fasting insulin, on one hand, and diastolic blood pressure changes and hypertension, on the other, could not be explained by confounding effects of body mass index, waist/hip ratio, or weight gain. These findings are consistent with the hypothesis that fasting insulin levels may be one predisposing factor in the etiology of hypertension.

Fasting Serum Insulin Concentration and Early Insulin Response as Risk Determinants for Developing Diabetes

Among a cohort of 348 women aged 50 on entering a 12‐year prospective study, the incidence of diabetes was increased (17.1%) during follow‐up in those who initially had fasting glucose concentration above the upper quintile, a fasting serum insulin concentration above the upper quintile (14.9%), a disappearance rate of glucose below the lowest quintile in an IV glucose tolerance test (12.7%), or early insulin response below the lowest quintile (17.1%). The incidence in all women was 4.9%. By multivariate analysis, the highest risk was for high fasting serum insulin concentration. Obesity and treatment with antihypertensive drugs further increased the risk. An initial low early insulin response was not however a prerequisite for the development of manifest diabetes. Determination of fasting insulin concentration, especially in overweight hypertensive subjects, is of value in order to find out which subjects are at high risk of developing diabetes.

Hemostatic and metabolic variables in women with polycystic ovary syndrome

OBJECTIVE To study whether a previously demonstrated increased morbidity in cardiovascular disease (CVD) and diabetes mellitus in women with polycystic ovary syndrome (PCOS) is associated with certain hemostatic variables that are known to be markers for CVD. DESIGN The study was a trans-sectional follow-up study from a cohort of women with PCOS. SETTING The women with PCOS were recruited from hospital clinics and referents were randomized from a population study of women from the same area. PARTICIPANTS The investigation involved 28 women aged 43 to 62 years diagnosed to have PCOS on ovarian histopathology at wedge resection 25 to 34 years previously and 56 referents who were matched by age and body mass index. MAIN OUTCOME MEASURES In connection with a clinical investigation, the hemostatic variables fibrinogen, von Willebrand factor antigen, factor VII procoagulant activity, factor VII antigen, and plasminogen activator inhibitor as well as the metabolic variables serum insulin and serum triglycerides were assayed. RESULTS There was a strong positive correlation between serum concentrations of triglyceride, basal insulin, and abdominal obesity on the one hand, and plasminogen activator inhibitor, fibrinogen, and von Willebrand factor on the other, among women with PCOS as well as among referents. There were significantly higher mean concentrations of fibrinogen and factor VII:Ag among referents, but the mean values of most hemostatic variables studied showed no differences between the groups. CONCLUSION Women with an altered metabolic profile were also found to have affected hemostatic factors, but PCOS in itself did not seem to influence them.