Christina Nerbrand

Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure

Cadmium is a well-known nephrotoxic agent in food and tobacco, but the exposure level that is critical for kidney effects in the general population is not defined. Within a population-based women’s health survey in southern Sweden (Women’s Health in the Lund Area, WHILA), we investigated cadmium exposure in relation to tubular and glomerular function, from 1999 through early 2000 in 820 women (71% participation rate) 53–64 years of age. Multiple linear regression showed cadmium in blood (median, 0.38 μg/L) and urine (0.52 μg/L; density adjusted = 0.67 μg/g creatinine) to be significantly associated with effects on renal tubules (as indicated by increased levels of human complex-forming protein and N-acetyl-β-d-glucosaminidase in urine), after adjusting for age, body mass index, blood lead, diabetes, hypertension, and regular use of nephrotoxic drugs. The associations remained significant even at the low exposure in women who had never smoked. We also found associations with markers of glomerular effects: glomerular filtration rate and creatinine clearance. Significant effects were seen already at a mean urinary cadmium level of 0.6 μg/L (0.8 μg/g creatinine). Cadmium potentiated diabetes-induced effects on kidney. In conclusion, tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk.

Cadmium-induced effects on bone in a population-based study of women

High cadmium exposure is known to cause bone damage, but the association between low-level cadmium exposure and osteoporosis remains to be clarified. Using a population-based women’s health survey in southern Sweden [Women’s Health in the Lund Area (WHILA)] with no known historical cadmium contamination, we investigated cadmium-related effects on bone in 820 women (53–64 years of age). We measured cadmium in blood and urine and lead in blood, an array of markers of bone metabolism, and forearm bone mineral density (BMD). Associations were evaluated in multiple linear regression analysis including information on the possible confounders or effect modifiers: weight, menopausal status, use of hormone replacement therapy, age at menarche, alcohol consumption, smoking history, and physical activity. Median urinary cadmium was 0.52 μg/L adjusted to density (0.67 μg/g creatinine). After multivariate adjustment, BMD, parathyroid hormone, and urinary deoxypyridinoline (U-DPD) were adversely associated with concentrations of urinary cadmium (p < 0.05) in all subjects. These associations persisted in the group of never-smokers, which had the lowest cadmium exposure (mainly dietary). For U-DPD, there was a significant interaction between cadmium and menopause (p = 0.022). Our results suggest negative effects of low-level cadmium exposure on bone, possibly exerted via increased bone resorption, which seemed to be intensified after menopause. Based on the prevalence of osteoporosis and the low level of exposure, the observed effects, although slight, should be considered as early signals of potentially more adverse health effects.

Stroke Incidence and Survival in the Beginning of the 21st Century in Southern Sweden Comparisons With the Late 20th Century and Projections Into the Future

Background and Purpose— We report trends of stroke incidence and survival up to year 2001/2002 in Lund-Orup, Sweden, and projections of future stroke incidence in Sweden. Methods— Lund Stroke Register, a prospective population-based study, included all first-ever stroke patients, between March 1, 2001 and February 28, 2002, in the Lund-Orup health care district. Institution-based studies for 1983 to 1985 and 1993 to 1995 were used for comparison. We calculated age-standardized incidence and Cox proportional hazards analysis of survival (stroke subtype, sex, age group, and study period in the analysis). Minimum follow-up was 46 months. Based on our register’s stroke incidence and the official Swedish population projection, a projection for future stroke incidence on a national basis was calculated. Results— We included 456 patients with first-ever stroke in 2001/2002. The age-standardized incidence (to the European population) was 144 per 100 000 person-years (95%CI 130 to 158) in 2001/2002, 158 (95%CI 149 to 168) in 1993 to 1995, and 134 (95%CI 126 to 143) in 1983 to 1985. Cox proportional hazard analysis indicated decreased risk of death after stroke in 2001/2002 (hazard ratio 0.80; 95%CI 0.67 to 0.94) compared with 1993 to 1995. Up to year 2050, the annual number of new stroke patients in Sweden may increase by 59% based solely on demographic changes. Conclusions— Despite possible underestimation of stroke incidence during the previous institution-based studies, the increased stroke incidence between 1983 to 1985 and 1993 to 1995 did not continue in 2001/2002. The long-term survival after stroke continues to improve. As the elderly population is growing in Sweden, stable incidence and increasing survival will result in a rapidly increasing prevalence of stroke patients in Sweden.

Socio‐demographic and psychosocial factors are associated with features of the metabolic syndrome. The Women's Health in the Lund Area (WHILA) study

Aim: The aim was to analyse any associations between socio‐demographic and psychosocial factors and different features of the metabolic syndrome in a geographically well‐defined population of middle‐aged women.

Menopause-related symptoms: what are the background factors? A prospective population-based cohort study of Swedish women (The Women's Health in Lund Area study).

OBJECTIVE The purpose of this study was to analyze the influence of sociodemographic characteristics and environmental factors on self-reported menopause-related symptoms among middle-aged Swedish women. STUDY DESIGN Women who were born in the years 1935 to 1945 and who were living in the Lund area of southern Sweden were investigated. Each woman completed a generic questionnaire and underwent a personal interview that pertained to sociodemographic characteristics, lifestyle, and current health-related problems. With these background factors, the frequency and intensity of hot flushes and vaginal dryness were determined; risk factor analysis was evaluated with the use of the multiple regression models. RESULTS There were 6917 participants, with a response rate of 64%. A lower risk for hot flushes was related to older age, high education, and vigorous physical exercise. The major risk factors for vasomotor complaints were current weight gain, part-time employment, oophorectomy, unhealthy lifestyle, and concomitant health problems. Light smoking, late age of menopause, higher education, and excessive weight reduced the risk of vaginal dryness. However, older age, marriage, and chronic diseases negatively affected vaginal complaints. The background factors had less impact on symptoms in women who used hormone replacement therapy. CONCLUSION Sociodemographic characteristics, lifestyle, and concomitant health problems appear to be important modifiable determinants for menopause-related symptoms.

Overactive bladder: prevalence, risk factors and relation to stress incontinence in middle‐aged women

Objective  To investigate the prevalence of and factors associated with overactive bladder in middle‐aged women.

Important factors for use of hormone replacement therapy: a population-based study of Swedish women. The Women's Health in Lund Area (WHILA) Study

Objective: The aim of this study was to delineate the use of hormone replacement therapy (HRT) among women who were born between December 2, 1935, and December 1, 1945, and living in the Lund area of southern Sweden and to analyze factors that contribute to the acceptance and continuation of HRT. Methods: All women received a generic questionnaire pertaining to demographic background, lifestyle, health behavior, and climacteric symptoms and underwent a personal interview. An interim analysis was carried out on 3,900 women. We mailed a hormone questionnaire to the women who were using HRT (n = 1,875). This hormone questionnaire covered, for example, menopausal status, complaints, and alterations in and efficacy of HRT use, as well as the reasons for discontinuing HRT use. Results: A total of 1,415 (76%) women answered the hormone questionnaire. Forty‐eight percent were HRT ever users, and 32% were current users. Mean duration of HRT use was 47 months. The most common incentives for HRT use were alleviation of menopausal symptoms (72%) and prevention of bone loss (50%) and/or cardiovascular disease (31%). Forty‐seven percent of HRT users reported that they had changed regimens at least once. HRT users had higher education, full‐time work, and a higher consumption of alcohol but less consumption of cigarettes. They reported higher frequencies of climacteric symptoms, past histories of premenstrual syndrome, use of oral contraceptives, and hysterectomy. They also had a higher consumption of healthcare resources. A total of 177 women withdrew from therapy. The most common reasons for discontinuation of HRT were weight gain, anxiety of cancer, bleeding, breast tenderness, and emotional problems. Compared with current users, past users had less positive as well as fewer negative effects of HRT. Several variables contributed to compliance, including education, full‐time work, regular exercise, low frequency of persistent climacteric symptoms, and alteration of regimens. Conclusion: Education, working conditions, lifestyle, interest in prevention, and severity of the climacteric symptoms are determinants for both acceptance of and compliance with HRT. (Menopause 2000;7:273‐281.

Lund Stroke Register: hospitalization pattern and yield of different screening methods for first-ever stroke

Objectives –  To explore case ascertainment, hospitalization, characteristics of both hospitalized and non‐hospitalized patients in a population‐based group of stroke patients.

A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden)

Objectives: Reports suggest that combined estrogen plus progestin hormone replacement therapy (HRT) confers a higher breast cancer risk than estrogen alone. We aimed to establish whether breast cancer risk depends on the type of HRT formula. Methods: The cohort consisted of 6586 women, aged 50–64 years, from the Lund area, Sweden, with no reported breast cancer upon inclusion. We obtained information such as HRT use through a questionnaire between December 1995 and February 2000. New breast cancers were identified through the South Swedish tumor registry. Results: Between inclusion and December 2001, 101 women developed breast cancer. Only ever use of the continuous combined estrogen plus progestin (CCEP) formula differed between cases and controls (45.2% versus 23.5%; p = 0.000001). Compared with never users, exclusive CCEP users had the highest age-adjusted hazard ratio HR 3.3 (95% CI: 1.9–5.6; p < 0.001), followed by users of CCEP in addition to other HRT formulas HR 2.8 (95% CI: 1.4–5.5; p = 0.003). No significant increase was seen in women who exclusively used other HRT formulas. Conclusion: Women who used CCEP had over three times the risk of developing breast cancer compared with never users and twice the risk compared with users of other types of HRT.

Barriers to adherence to hypertension guidelines among GPs in southern Sweden: A survey.

Objective. To evaluate barriers to adherence to hypertension guidelines among publicly employed general practitioners (GPs). Design. Questionnaire-based survey distributed to GPs in 24 randomly selected primary care centres in the Region of Skåne in southern Sweden. Subjects. A total of 109 GPs received a self-administered questionnaire and 90 of them responded. Main outcome measures. Use of risk assessment programmes. Reasons to postpone or abstain from pharmacological treatment for the management of hypertension. Results. Reported managing of high blood pressure (BP) varied. In all, 53% (95% CI 42–64%) of the GPs used risk assessment programmes and nine out of 10 acknowledged blood pressure target levels. Only one in 10 did not inform the patients about these levels. The range for immediate initiating pharmacological treatment was a systolic BP 140–220 (median 170) mmHg and diastolic BP 90–110 (median 100) mmHg. One-third (32%; 95% CI 22–42%) of the GPs postponed or abstained from pharmacological treatment of hypertension due to a patients advanced age. No statistically significant associations were observed between GPs’ gender, professional experience (i.e. in terms of specialist family medicine and by number of years in practice), and specific reasons to postpone or abstain from pharmacological treatment of hypertension. Conclusion. These data suggest that GPs accept higher blood pressure levels than recommended in clinical guidelines. Old age of the patient seems to be an important barrier among GPs when considering pharmacological treatment for the management of hypertension.