Age and sex differences in the distribution and ultrasound morphology of carotid atherosclerosis: the Tromsø Study

Atherosclerosis begins early in life and is the major underlying cause of cardiovascular morbidity and death. Yet, population-based information on age and sex differences in the extent and morphology of atherosclerosis throughout life is scarce. Carotid atherosclerosis can be visualized with B-mode ultrasound and is a marker of atherosclerosis elsewhere in the circulation. We assessed both the prevalence and the morphology of carotid atherosclerosis by B-mode ultrasound in 3016 men and 3404 women, 25 to 84 years old, who participated in a population health survey. The participation rate was 88%. Plaque morphology was graded according to whether a plaque was predominantly soft (echolucent) or hard (echogenic). Atherosclerotic plaques were found in 55.4% of the men and 45.8% of the women. In men, there was a linear increase with age in the prevalence of carotid atherosclerosis, whereas in women, there was a curvilinear age trend, with an inflection in the prevalence rate of women at approximately 50 years of age. The male predominance in atherosclerosis declined after the age of 50 years, the plaque prevalence being similar in elderly men and women. Men had softer plaques than women; this sex difference in plaque morphology increased significantly (P=0.005) with age. The sex difference in the prevalence of atherosclerosis and the female age trend in atherosclerosis show significant changes at the age of approximately 50 years, suggesting an adverse effect of menopause on atherosclerosis. The higher proportion of soft plaques in men compared with women increases with age and may partly account for the prevailing male excess risk of coronary heart disease in the elderly despite a similar prevalence of atherosclerosis in elderly men and women.     

Haemoglobin and anaemia in a gender perspective: the Tromsø Study

Abstract: Objectives: To examine the gender‐specific distribution of haemoglobin (Hb) and the World Health Organization (WHO) criteria for anaemia compared with the 2.5 percentile for Hb. Methods: A population‐based study from Tromsø, Northern Norway. All inhabitants above 24 yr were invited. In total, 26 530 (75%) had their Hb analysed. Results: The 2.5–97.5 percentile of Hb was 129–166 and 114–152 g/L for all men and women, respectively. In men, mean Hb decreased from 148 to 137 g/L between 55–64 and 85+ yr. In women, mean Hb increased from 132 to 137 g/L between 35–44 and 65–74 yr and then decreased to 131 g/L among the oldest. Using the WHO criteria for anaemia (Hb: <130 and <120 g/L, men and women respectively), the prevalence of anaemia in men increased with age from 0.6% aged 25–34 to 29.6% aged 85+. For women, the prevalence of anaemia varied from 9.1%, 2.2% and 16.5% in the age groups of 35–44, 55–64 and 85+ yr, respectively. The WHO criteria gave a two to three times higher prevalence of anaemia compared with the 2.5 percentile of Hb in women, but the difference was small in men. Poor self‐rated health was not associated with low values of Hb in women. In men, there was an association in some age groups. Conclusion: The WHO criteria for anaemia and the 2.5 percentile for Hb corresponded well for men, but not for women. The WHO criteria of anaemia may result in medicalization of healthy women.     

Uric acid is associated with microalbuminuria and decreased glomerular filtration rate in the general population during 7 and 13 years of follow-up: The Tromsø Study

Background

The role of uric acid in development of renal dysfunction (RD) remains controversial. Earlier studies have reported inconsistent results, possibly because of their varying ability to adjust for confounding. The impact of longitudinal change in uric acid on renal outcome has not been assessed previously. We aimed to study the impact of change in serum uric acid (SUA) as well as baseline SUA on the development of RD.

Methods

In a prospective cohort study, we assessed the associations between change in SUA during follow-up, baseline SUA and RD (defined as albumin-creatinine-ratio (ACR) ≥1.13 mg albumin/mmol creatinine and/or eGFR?<?60 ml/min/1.73 m²) in a large cohort from a general population participating in the Tromsø Study (n?=?2637). Participants were stratified according to tertiles of change in SUA between baseline (1994/95) and follow-up 13 years later. (upper tertile: SUA increasing group, two lower tertiles: SUA non-increasing group). Logistic regression analysis was applied with RD and each component of RD after 7 and 13 years as the dependent variables. Adjustments were made for baseline eGFR, cardiovascular risk factors, and the use of antihypertensive drugs including diuretics.

Results

After excluding participants with RD at baseline, SUA increasers, compared to SUA non-increasers, had a doubled risk of RD after 7 years (odds ratio 2.00, (95 % CI 1.45, 2.75)). Odds ratio for RD in SUA increasers after 13 years was 2.18 (95 % CI 1.71, 2.79). The risk of developing ACR ≥1.13 mg/mmol alone was not significantly increased after 7 years (odds ratio 1.30 (95 % CI 0.90, 1.89), but after 13 years (odds ratio 1.43 (95 % CI 1.09, 1.86)). An increase in baseline SUA of 59 μmol/L (1 mg/dL) gave an odds ratio for RD after 13 years of 1.16 (95 % CI 1.04, 1.29).

Conclusion

An increase in SUA during follow-up was associated with an increased risk of developing RD after 7 and 13 years.

     

Determinants of progression from impaired fasting glucose and impaired glucose tolerance to diabetes in a high-risk screened population: 3 year follow-up in the ADDITION study,Denmark

Aims/hypothesis We sought to identify determinants of progression from impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) to diabetes in high-risk screened individuals. Methods In general practices in Denmark, stepwise screening for type 2 diabetes mellitus in persons aged 40 to 69 years included a risk questionnaire, random blood glucose, HbA_1c, fasting blood glucose and an OGTT. The 1,821 individuals with IGT or isolated IFG (WHO 1999) were re-invited after 1 and 3 years. Follow-up data on glucose measurements were available in 1,510 individuals and additional clinical data in 1,002 collected at the 3-year visits. Regression models using interval censoring were used. Results Progression rates from IFG and IGT to diabetes over 3.5 years were 11.8 and 17.0 per 100 person-years, respectively and were particularly high in the first year. Baseline determinants of progression were: IFG: glucose measures, BMI [per kg/m², rate ratio (RR) 1.04 (95% CI, 1.01–1.08)] and triacylglycerol [per twofold increase, RR 2.19 (1.49–3.22)]; and IGT: glucose measures and known hypertension [RR 1.46 (1.11–1.93)]. Weight reduction and decreased triacylglycerol were inversely associated with development of diabetes in IFG individuals [per 1 kg/year, RR 0.81 (0.66–0.98) and per 1 mmol l⁻¹ year⁻¹, RR 0.08 (0.01–0.51), respectively], whereas in IGT participants only weight reduction was inversely associated [per 1 kg/year, RR 0.80 (0.67–0.96)]. Conclusions/interpretation Higher levels of glucose measures, larger BMI, known hypertension and hypertriacylglycerolaemia are significant determinants of progression in high-risk screened individuals. Weight loss of 1 kg/year or reduction of hypertriacylglycerolaemia markedly reduced the risk of diabetes.     

Association of impaired fasting glucose and coronary artery calcification as a marker of subclinical atherosclerosis in a population-based cohort—results of the Heinz Nixdorf Recall Study

Aims/hypothesis  Atherosclerosis and cardiovascular diseases are often present at the time of diagnosis of type 2 diabetes mellitus. Whether subclinical atherosclerosis can be detected in the pre-diabetic (borderline fasting hyperglycemia) state is not clear. This study investigated the association of impaired fasting glucose (IFG) and coronary artery calcification (CAC), a marker of subclinical atherosclerosis, among participants without a history of coronary heart disease or manifest diabetes mellitus. Methods  Study participants (aged 45–75 years) of the population-based Heinz Nixdorf Recall Study were categorised into those with normal fasting glucose (glucose <6.1 mmol/l) and those with IFG (glucose ≥6.1 to <7.0 mmol/l), excluding participants with a history of CHD or diabetes mellitus. CAC was assessed by electron-beam computed tomography, and risk factors were assessed by extended interviews, anthropometric measurements and laboratory tests. Various CAC cut-off points were used in multiple logistic and ordinal logistic regression models to estimate ORs and 95% CIs. Results  Of the 2,184 participants, more men had IFG than did women (37% vs 22%). Participants with IFG showed a higher prevalence of CAC  > 0 (men OR 1.90, 95% CI 1.33–2.70; women 1.63, 1.23–2.15). Risk factor adjustment weakened this association in both sexes (men 1.63, 1.12–1.36; women 1.26, 0.93–1.70). When the age- and sex-specific 75th percentile was used as the cut-off point for CAC, the association further decreased in men (1.10, 0.81–1.50), but became stronger in women (1.41, 1.02–1.94). Conclusions/interpretation  These data support the hypothesis that CAC is already present in the pre-diabetic state and that IFG has a modest and independent impact on the atherosclerotic process. Biological sex appears to modify the association between IFG and CAC. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Gestational retinal microvasculature and the risk of 5 year postpartum abnormal glucose metabolism

Aims/hypothesis

Changes in retinal microvasculature may reflect insulin resistance. We examined the association of changes in retinal microvasculature during pregnancy and risk of subsequent abnormal glucose metabolism in a cohort of mothers at baseline and 5 years postpartum.

Methods

Of the participants from the Singapore birth cohort (Growing Up in Singapore Towards Healthy Outcomes [GUSTO]), 276 mothers attended both baseline (at 26–28 weeks of gestation) and follow-up (5 year postpartum) visits. At baseline we performed retinal photography and assessed retinal microvascular variables using a validated grading system. At follow-up, we assessed glucose tolerance using a 75 g OGTT. We defined abnormal glucose metabolism if participants: (1) had onset of gestational diabetes mellitus (GDM) in subsequent pregnancies within a 5 year follow-up period (n = 103) or (2) had prediabetes (impaired fasting glucose, impaired glucose tolerance or HbA_1c 5.7–6.4% [39–46 mmol/mol]) and diabetes diagnosed at the 5 year follow-up visit (n = 84), according to WHO guidelines.

Results

The incidence of GDM in subsequent pregnancy and abnormal glucose metabolism 5 years postpartum was 25.2% and 30.4%, respectively. Each 10 μm widening in retinal venular calibre was associated with a significant risk of postpartum abnormal glucose metabolism (RR 1.2 [95% CI 1.0, 1.5]), independent of maternal age, college education, ethnicity, pre-pregnancy BMI and GDM at baseline. Narrower retinal arteriolar calibre and venular branching angle at baseline was associated with a higher insulin resistance index (1.4 [95% CI 1.1, 1.7] and 1.3 [95% CI 1.1, 1.6], respectively) at follow-up.

Conclusions/interpretation

Retinal microvasculature in pregnant women was associated with abnormal glucose metabolism 5 years postpartum. Alteration of microvascular structure during pregnancy may signal subclinical changes that underlie the development of prediabetes and diabetes.

     

Age and sex differences in the relationship between inherited and lifestyle risk factors and subclinical carotid atherosclerosis: the Tromsø study

BACKGROUND: Ultrasound measurement of carotid artery intima-media thickness (IMT) is regarded as a valid index of atherosclerosis. Age and sex differences in the distribution of, and risk factors for, IMT have not been investigated thoroughly. METHODS: In 1994-1995 a total of 6408 men and women aged 25-84 years living in the municipality of Troms?, Norway, underwent ultrasound examination of carotid artery IMT and measurements of cardiovascular risk factors. RESULTS: Age, systolic blood pressure, total cholesterol, HDL cholesterol, body mass index, and smoking were independent predictors of IMT in both sexes. Fibrinogen levels and physical activity were associated with IMT in men only, whereas triglyceride levels were associated with IMT independently of HDL cholesterol in women only. A family history of cardiovascular disease (CVD) was an independent predictor of IMT in both sexes, also when controlling for traditional CVD risk factors. The magnitude of the association between most risk factors and IMT did not differ depending on age, but the effects of physical activity and triglycerides were more pronounced at higher age. CONCLUSION: These data suggest that there are significant age and sex differences in the distribution and the determinants of subclinical atherosclerosis.     

The associations of age,lifestyle factors and chronic disease with testosterone in men: the Tromsø Study

OBJECTIVE: To study whether lifestyle factors and/or chronic disease are associated with the age-related decline of total and free testosterone in men, or if these factors might be associated with the variation of total and free testosterone but not with their age-related decline. DESIGN: A population-based, cross-sectional study was used. METHODS: Total testosterone and sex hormone binding globulin (SHBG) levels were analyzed and free testosterone levels were calculated in 1563 men participating in the Troms? study in 1994/1995. Anthropometric characteristics were also measured and two standardized questionnaires completed, including lifestyle factors and medical history. The data were analyzed with multiple linear regression analysis of covariance, and logistic regression. RESULTS: Total and free testosterone were inversely associated (P=0.001 and P<0.001), while SHBG was positively associated (P<0.001) with age. Body mass index (BMI) was inversely associated with total (P<0.001) and free (P=0.016) testosterone and SHBG (P<0.001). Both total and free testosterone were positively associated with tobacco consumption (P<0.001 and P=0.004) and total testosterone was positively associated with coffee consumption (P<0.001). SHBG was positively associated with smoking (P=0.004) and coffee consumption (P<0.001). Men who reported having had a stroke or having a cancer diagnosis had lower levels of total testosterone (P<0.001 and P<0.01) and free testosterone (P<0.01). CONCLUSIONS: BMI and smoking are independent contributors to the variation of total and free testosterone and SHBG levels, and coffee consumption to the variation of total testosterone and SHBG. Thus, lifestyle factors can have a direct effect on circulating levels of free endogenous sex hormones and to total levels due to the effect on SHBG levels.     

Cause-specific mortality trends in a nationwide population-based cohort of childhood-onset type 1 diabetes in Japan during 35 years of follow-up: the DERI Mortality Study

Aims/hypothesis

The aim of this study was to investigate long-term, cause-specific mortality trends among patients with childhood-onset type 1 diabetes in Japan.

Methods

Individuals included in the study had received a diagnosis of type 1 diabetes at age <18 years between 1965 and 1979. All individuals were followed up for their survival status until 1 January 2005. The causes of death were divided into end-stage renal disease (ESRD), acute diabetic complications (ADC), accident/suicide, cardiovascular disease (CVD), infections, cancers, others (non-diabetic/diabetic) and unknown. The cause-specific mortality trends were expressed according to the follow-up period and year of diagnosis.

Results

A total of 1,385 patients were enrolled in the study, and the survival status of 1,324 was confirmed. Mortality rate at the 35 year follow-up (per 100,000 person-years) was 659.3, and the standardised mortality ratio (SMR) was 10.7. The SMR at the 25 year follow-up markedly declined from 19.3 in the 1965–1969 diagnosis group to 6.6 in the 1975–1979 diagnosis group. Approximately 40% died of ADC among those with <10 years of follow-up. A similar proportion of individuals died of ESRD among those with 10–19 years of follow-up. The longer the duration of follow-up, the lower the mortality from ADC and the greater the mortality from CVD.

Conclusions/interpretation

In Japanese people with childhood-onset type 1 diabetes of more than 20 years of duration, CVD was the leading cause of death, as is the case among similar white people. The longer the duration of diabetes, the more attention should be paid to preventing CVD.     

Association of fasting serum insulin and cancer mortality in a healthy population – 28-year follow-up of the French TELECOM Study

Aims

Epidemiologic, pharmacoepidemiologic and pathophysiologic evidence points consistently to an association between type 2 diabetes and cancer. This association could be explained by hyperinsulinemia induced by insulin resistance. We studied the association between fasting serum insulin (FSI) and cancer mortality in a population of non-diabetic individuals.

Behavior and health beliefs as predictors of HIV testing among women: a prospective study of observed HIV testing

Much of the research examining predictors of HIV testing has used retrospective self-report to assess HIV testing. Findings. therefore, may be subject to recall bias and to difficulties determining the direction of associations. In this prospective study, we administered surveys to women in community clinics to identify predictors of subsequent observed HIV testing, overcoming these limitations. Eighty-three percent were tested. In the adjusted multivariable model, being born in the U.S., perceived benefits of testing, worries about being infected with HIV, having had more than 15 lifetime sexual partners, and having had one or more casual sexual partners in the previous three months predicted acceptance of testing. Perceived obstacles to testing predicted non-acceptance. Those who had never been tested for HIV and those tested two to five years previously had greater odds of test acceptance than those who had been tested within the last year. The findings from this study with observed testing as the outcome, confirm some of the results from retrospective, self-report studies. Participants made largely rational decisions about testing, reflecting assessments of their risk and their history of HIV testing. Health beliefs are potentially modifiable through behavioral intervention, and such interventions might result in greater acceptance of testing.

Abbreviations: HIV: human immunodeficiency virus; AIDS: acquired immune deficiency syndrome; CDC: Centers for Disease Control and Prevention; ACASI: audio computer-assisted self-interview; TRA: theory of reasoned action; HBM: Health Belief Model; STI: sexually transmitted infection; STD: Sexually Transmitted Disease; AOR: adjusted odds ratio; CI: confidence interval     

Haematological malignancies in a general population,based on information collected from a population study,hospital records,and the Cancer Registry of Norway: the Tromsø Study

Abstract: Objectives : To investigate the prevalence and incidence of haematological malignancies, and to compare the rates found with those reported from the Cancer Registry of Norway. Methods : Three sources of information were used: (1) automated blood cell counts from 27 145 persons older than 24 yr (72% of those invited), participating in a population study (the Tromsø Study 1994–95); (2) patient medical records at the University Hospital of Tromsø during 1991–96; (3) the Cancer Registry of Norway. Results : (1) In the population study, 13 new cases of haematological malignancies were diagnosed. For five of these the early detection was probably beneficial. (2) From the hospital records another 59 participants and 36 non‐participants to the population study were found to have haematological malignancies. (3) Additionally, six cases were identified from the Cancer Registry. Totally, we thus identified 114 period prevalent cases, of which 86% had been reported to the Cancer Registry. Age‐adjusted period prevalence of haematological malignancies was 4.7‰ in men and 2.9‰ in women. The prevalence increased with age. There were 84 cases with leukaemia, lymphoma, or multiple myeloma diagnosed at any time and still alive at 31 December 1996 (point prevalence 2.2‰). Our estimated incidence of haematological malignancies did not differ significantly from that reported from the Cancer Registry. Conclusion : We found approximately the same rates of haematological malignancies as the Cancer Registry, although an underreporting of 14% to the Cancer Registry was detected. The point prevalence of leukaemia, lymphoma, and multiple myeloma was 2.2%.     

Seasonal variation of testosterone and waist to hip ratio in men: the Tromsø study

Studies of seasonal variation in male testosterone levels show contradictory results. We report here a cross-sectional study of the seasonal variation in total and free testosterone, LH, and SHBG levels in 1548 men living in north Norway, a population exposed to a wide seasonal variation in temperature and daylight. Total testosterone showed a bimodal seasonal variation (P < 0.001) with a small peak in February, the nadir in June, and a more prominent peak in October and November. Free testosterone also showed a significant seasonal pattern (P < 0.001), with the peak in December and the nadir in August. These patterns persisted after adjusting for age and waist to hip ratio (P < 0.001). Lowest testosterone levels occurred in months with the highest temperatures and longest hours of daylight. Waist to hip ratio paralleled the change in daylight and temperature, with the highest values during the summer and was thus inversely related to the seasonal testosterone variation. The variations in hormone levels were large, with a 31% difference between the lowest and highest monthly mean level of free testosterone. Prospective studies are needed to establish the direction of the association and its etiology.     

Prolonged sitting may increase diabetes risk in physically inactive individuals: an 11 year follow-up of the HUNT Study,Norway

Aims/hypothesis

We examined the association between sitting time and diabetes incidence, overall and by strata of leisure-time physical activity and BMI.

Methods

We followed 28,051 adult participants of the Nord-Trøndelag Health Study (the HUNT Study), a population-based study, for diabetes incidence from 1995–1997 to 2006–2008 and estimated HRs of any diabetes by categories of self-reported total daily sitting time at baseline.

Results

Of 28,051 participants, 1253 (4.5%) developed diabetes during 11 years of follow-up. Overall, sitting ≥8 h/day was associated with a 17% (95% CI 2, 34) higher risk of developing diabetes compared with sitting ≤4 h/day, adjusted for age, sex and education. However, the association was attenuated to a non-significant 9% (95% CI ?5, 26) increase in risk after adjustment for leisure-time physical activity and BMI. The association between sitting time and diabetes risk differed by leisure-time physical activity (p _Interaction?=?0.01). Among participants with low leisure-time physical activity (≤2 h light activity per week and no vigorous activity), sitting 5–7 h/day and ≥8 h/day were associated with a 26% (95% CI 2, 57) and 30% (95% CI 5, 61) higher risk of diabetes, respectively, compared with sitting ≤4 h/day. There was no corresponding association among participants with high leisure-time physical activity (≥3 h light activity or >0 h vigorous activity per week). There was no statistical evidence that the association between sitting time and diabetes risk differed by obesity (p _Interaction?=?0.65).

Conclusions/interpretation

Our findings suggest that total sitting time has little association with diabetes risk in the population as a whole, but prolonged sitting may contribute to an increased diabetes risk among physically inactive people.