Biomedical subjects

Lars Janzon

Publications and source records attributed to Lars Janzon.

51 records · Page 3Linked to original sources

PubMed2003

Postmenopausal breast cancer risk in relation to sex steroid hormones, prolactin and SHBG (Sweden).

OBJECTIVE: High levels of sex steroid hormones and prolactin have been suggested to enhance breast cancer development. Low levels of SHBG may indicate high levels of (bio-available) steroid hormones. The present study investigates whether high levels of sex steroid hormones and prolactin, and/or low levels of SHBG, are associated with high breast cancer risk. METHODS: Blood samples were collected in about 65,000 women participating in two population-based prospective cohort studies in Sweden. Follow-up yielded 173 postmenopausal breast cancer cases who had not been exposed to HRT. Levels of estrone, estradiol, SHBG, FSH, prolactin, testosterone, androstenedione and DHEAs were analysed in cases and 438 controls. Logistic regression analysis yielded odds ratios (ORs), with 95% confidence intervals, adjusted for potential confounders. RESULTS: The risk of breast cancer was associated with the highest versus lowest quartiles of estrone, OR: 2.58 (1.50-4.44), estradiol (dichotomised: high versus low) (1.73: 1.04-2.88), and testosterone (1.87: 1.08-3.25). High risks, although not statistically significant, were seen for androstenedione (1.58: 0.92-2.72) and DHEAs (1.62: 0.89-2.72). No strong associations were seen between SHBG or prolactin and risk of breast cancer. CONCLUSIONS: High levels of estrone, estradiol, testosterone, and possibly androstenedione and DHEAs, in postmenopausal women are associated with a high risk of subsequent breast cancer.

Androstenedione↗

PubMed2003

Hypertension and changes of cognitive function in 81-year-old men: a 13-year follow-up of the population study "Men born in 1914", Sweden.

BACKGROUND: The relationship between blood pressure levels and decline of cognition has been discussed previously, but little is known about the confounding effect of lifestyle factors, antihypertensive treatment and disease in the elderly. OBJECTIVE: To examine the association between systolic (SBP) and diastolic (DBP) blood pressure, changes of DBP and SBP and hypertension (HT) on cognitive function, while controlling for confounding factors. DESIGN: A longitudinal cohort study of men born in 1914 and residing in the municipality of Malmö studied at age 68 and 81 years. SETTING: Probands invited to a university clinic. SUBJECTS: One hundred and eighty-six out of 281 invited men still alive in 1995/6 participated in the most recent follow-up. MAIN OUTCOME: Change of the cognitive performance in the verbal (Paired Associates and Synonyms), spatial (Block Design and Benton Visual Retention test) and speed (Digit Symbol Substitution) functions. RESULTS: DBP by tertiles at 68 years, but not HT, was inversely related to verbal, spatial and speed performance at 81 years. Only spatial function was related to SBP at 68 years. The association between DBP and SBP by tertiles, and spatial functions (Block Design and Benton Visual Retention test) remained after controlling for education, marital status, smoking, alcohol and physical activity, and intermediates such as arteriosclerotic manifestations (block design, beta = 0.17; = 0.029) in multiple regression models. A decrease in DBP was likewise related to spatial (beta = 0.16; = 0.049) and speed performance (beta = 0.17; = 0.039) in the same regression model. CONCLUSIONS: Evidence is found to support the hypothesis that hypertension, especially high DBP in late midlife, is associated with a decline in spatial performance of cognitive functions in elderly men.

Aged↗

PubMed2003

Inflammation-sensitive plasma proteins and incidence of myocardial infarction in men with low cardiovascular risk.

OBJECTIVE: Myocardial infarction (MI) is sometimes experienced by individuals without any traditional risk factor. This prospective study explored whether incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and serum lipids is related to inflammation-sensitive plasma proteins (ISPs). METHODS AND RESULTS: Five ISPs (alpha1-antitrypsin, haptoglobin, ceruloplasmin, fibrinogen, orosomucoid) were analyzed in 6075 men, 47+/-3.6 years old. A low-risk group (no traditional risk factor, n=1108) and a high-risk group (> or =2 major risk factors, n=1011) were defined. Incidence of MI (n=227) was monitored over 18.1+/-4.3 years of follow-up. In the low-risk group, the age-adjusted relative risks (RRs) were 1.00 (reference), 1.9 (95% CI, 0.8 to 4.2), 1.8 (95% CI, 0.6 to 5.4), and 2.9 (95% CI, 1.05 to 8.1), respectively, for men with 0, 1, 2 and > or =3 ISPs in the top quartile (trend: P=0.03). In this group, the increased risk was observed only after > or =10 years of follow-up. In the high-risk group, the age-adjusted RRs were 1.00, 1.4 (95% CI, 0.9 to 2.2), 1.9 (95% CI, 1.2 to 3.1), and 2.0 (95% CI, 1.3 to 3.1), respectively, for men with 0, 1, 2, and > or =3 ISPs in the top quartile (trend: P=0.0004). CONCLUSIONS: Incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and lipids was related to ISPs. The causes for this relationship remain to be explored.

Acute-Phase Proteins↗

PubMed2003

Adaptive behavior in stressful situations in relation to postinfarction mortality results from prospective cohort study "Men Born in 1914" in Malmo, Sweden.

The serial Color Word Test, which is a semi-experimental way to differentiate adaptive behavior in stressful situations, was administered at baseline to men participating in the prospective cohort study "Men born in 1914". During follow-up, from 1982-1983 until December 31, 1996, 133 men experienced a myocardial infarction. Four patterns of adaptive behavior in 2 separate dimensions, the Variability and the Regression, can be discerned during testing. These patterns were compared regarding outcome following the myocardial infarction. The Cumulative-dissociative pattern of the Regression dimension was univariately associated with mortality within 28 days (OR 5.75, CI 1.85-17.88, p = .003). Dissociative (OR 3.87, CI 1.21-12.42, p = .023) and Cumulative-dissociative (OR 5.46, CI 1.66-17.96, p = .005) patterns, of the same dimension, were independently associated with mortality within one year. Specific difficulties in adaptation to stressful situations were associated with increased risk of death following a myocardial infarction. In this male sample, these difficulties could be identified with the serial Color Word Test.

Adaptation, Psychological↗

PubMed2003

Inflammation-sensitive plasma proteins, diabetes, and mortality and incidence of myocardial infarction and stroke: a population-based study.

This study explores the relationship of inflammation-sensitive plasma proteins (ISPs) with the prevalence of diabetes and the interrelationships between ISPs and diabetes in the prediction of death and incidence of myocardial infarction and stroke. Plasma levels of fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were assessed in 6,050 men, aged 28-61 years. All-cause and cardiovascular mortality and incidence of myocardial infarction and stroke were monitored over 18.7 +/- 3.7 years. Prevalence of diabetes (n = 321) was significantly associated with ISP levels among overweight and obese men but not among men with BMI <25 kg/m(2). The association was similar for insulin resistance according to homeostasis model assessment. High ISP levels (two or more ISPs in the top quartile) increased the cardiovascular risk among diabetic men. The risk factor-adjusted relative risks for cardiovascular mortality, myocardial infarction, and stroke were 2.8 (CI 1.8-4.5), 2.2 (1.5-3.2), and 2.5 (1.4-4.6), respectively, for diabetic men with high ISP levels (reference: nondiabetic men with low ISP levels). The corresponding risks for diabetic men with low ISP levels were 1.8 (1.1-3.0), 1.3 (0.8-2.1), and 1.2 (0.6-2.5), respectively. In conclusion, in this population-based cohort, diabetes was associated with increased ISP levels among overweight and obese men but not among men with normal weight. High ISP levels increased the cardiovascular risk similarly in diabetic as compared with nondiabetic men.

Blood Pressure↗

PubMed2003

Inflammation-sensitive plasma proteins are associated with future weight gain.

Cross-sectional studies have associated obesity and other components of the so-called metabolic syndrome with low-grade inflammation. The temporal and causal relations of this association have not been fully explored. This study explored whether elevated levels of inflammation-sensitive plasma proteins (ISPs) (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with future weight gain. Five ISPs were measured in 2,821 nondiabetic healthy men (38-50 years of age) who were reexamined after a mean follow-up of 6.1 years. Future weight gain was studied in relation to the number of elevated ISPs (i.e., in the top quartile). The proportion with a large weight gain (75th percentile >/= 3.8 kg) was 21.0, 25.9, 26.8, and 28.3%, respectively, among men with none, one, two, and three or more ISPs in the top quartile (P for trend 0.0005). This relation remained significant after adjustments for weight at baseline, follow-up time, height (at baseline and follow-up), physical inactivity (at baseline and follow-up), smoking (at baseline and follow-up), high alcohol consumption, and insulin resistance. The relations were largely similar for all individual ISPs. Elevated ISP levels predict a large weight gain in middle-aged men. This relation could contribute to the relation between inflammation, the metabolic syndrome, and cardiovascular disease.

Adult↗

PubMed2003

Antibodies against 5-hydroxymethyl-2'-deoxyuridine are associated with lifestyle factors and GSTM1 genotype: a report from the Malmö Diet and Cancer cohort.

Plasma autoantibodies (aAbs) against the oxidized DNA base derivative 5-hydroxymethyl-2'-deoxyuridine (5-HMdU) are potential biomarkers of cancer risk and oxidative stress. We examined their association with a number of cancer risk factors: smoking, alcohol habits, body fatness, and absence of the glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in a sample from the population-based Malmö Diet and Cancer cohort (Sweden). This was a cross-sectional study of 264 men and 280 women, 46-67 years of age. Anti-5-HMdU aAb concentration was determined by an ELISA. Data on tobacco exposure were collected through a questionnaire. Alcohol consumption was estimated by a modified diet history method. Body fatness was assessed by a bioimpedance method. The absence or presence of genes coding for GSTM1 and GSTT1 was determined in granulocyte DNA by a multiplex PCR technique. aAb titers were significantly greater in those with high alcohol consumption. Current smokers lacking GSTM1, particularly men, had greater aAb titers compared with nonsmokers or persons expressing GSTM1. Body fatness was inversely associated with antibody titers in men. GSTT1 genotype was not associated with aAb titers. Overall, women had higher aAb titers than men. Adjustment for potential confounders (history of chronic diseases, anti-inflammatory medication, and season of blood sampling) did not change the results. Our study shows that a high alcohol consumption, smoking in combination with lack of GSTM1, and low body fatness (in men) is associated with high titers of anti-5-HMdU aAbs in this population.

Age Distribution↗

PubMed2002

Blood pressure increase and incidence of hypertension in relation to inflammation-sensitive plasma proteins.

OBJECTIVE: The reasons for the relationship between inflammation-sensitive plasma proteins (ISPs) and incidence of cardiovascular diseases are poorly understood. This study explored the hypothesis that ISPs are associated with future hypertension and age-related blood pressure increase. METHODS AND RESULTS: Blood pressure and plasma levels of fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 2262 healthy men aged 35 to 50 years, initially without treatment for hypertension. The cohort was re-examined after 15.7 (+/-2.2) years. Incidence of hypertension and blood pressure increase was studied in relation to number of elevated proteins (ie, in the top quartile) at baseline. Among men without treatment for hypertension at follow-up, mean (+/-SD) increase in systolic blood pressure was 18.8+/-17, 19.2+/-17, 19.3+/-17, and 22.1+/-18 mm Hg, respectively, for men with 0, 1, 2, and > or =3 elevated proteins (P for trend=0.02, adjusted for confounders). The corresponding values for pulse pressure increase was 15.5+/-14, 15.8+/-14, 17.4+/-14, and 17.8+/-15 mm Hg, respectively (P=0.02). Incidence of hypertension (> or =160/95 mm Hg or treatment) and future blood pressure treatment showed similar associations with ISPs. Increase in diastolic blood pressure showed no association with ISPs. CONCLUSIONS: Plasma levels of ISPs are associated with a future increase in blood pressure. This could contribute to the relationship between ISP levels and cardiovascular disease.

Adult↗

PubMed2002

Molecular profiling of hepatotoxicity induced by a aminoguanidine carboxylate in the rat: gene expression profiling.

The hepatotoxicity of the aminoguanidine carboxylate 2-[1-[hydrazino(imino)methyl]hydrazino]acetic acid was characterized using oligonucleotide micro arrays, with the goal to select compounds from the same class with lower toxicity potential. The approach included a 14-day repeated- and a single-dose study in the rat as well as in vitro studies. Common gene expression changes could be followed from in vivo to in vitro studies. Anyhow, comparing the in vivo and in vitro response of the compound on gene expression, significant discrepancies were detected. Many of the genes whose mRNA levels were increased/decreased in the livers of the animals treated with toxic doses of the compound, were expressed at higher/lower levels in control hepatocytes than in control liver. The expression of the majority of these genes was not affected by in vitro treatment. These data question the use of gene expression analysis as a marker for drug response in vitro and illustrate the need of a careful characterization of in vitro systems. The results presented show that array-based gene expression analysis can lead to a better understanding of the molecular basis of drug-induced liver injury and, potentially, be used in the selection process for compounds and in the design of safer drugs.

Acetates↗

PubMed2002

Life-course perspective on socioeconomic differences in carotid atherosclerosis.

OBJECTIVE: Socioeconomic status (SES) in adulthood is known to be related to carotid atherosclerosis. However, few studies have tried to assess its association with SES from a life-course perspective. METHODS AND RESULTS: We examined the relationship between SES in childhood and in adulthood and carotid atherosclerosis in a general population of Swedish men and women. Carotid stenosis was determined by B-mode ultrasound. Results showed that women whose fathers' occupations involved unskilled manual labor had higher odds of carotid stenosis than did women whose fathers' occupations involved high- or medium-level nonmanual labor, even after adjustment for adult occupational status and risk factors (odds ratio 1.8, 95% CI 1.1 to 2.8). No such association appeared in men. Furthermore, the impact of life-course SES on atherosclerosis was examined by using an additive measure of one's combined SES during childhood and adulthood. Among women, the odds of carotid stenosis increased with a rise in exposure to low SES during the life-course (P for trend <0.001). In men, no such trend was found. CONCLUSIONS: The results indicate that the total life-course exposure to low SES, with contributions from childhood and adulthood, seems to play a role in atherogenesis in women. Such a pattern of association could not be shown in men.

Age Factors↗

PubMed2002

Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden.

OBJECTIVE: To examine the possible relationships of breast cancer risk to prediagnostic plasma levels of insulin; insulin-like growth factor-I (IGF-I); and IGF-binding proteins -1, -2, and -3. METHODS: Within two prospective cohorts in Umeå and Malmö we measured plasma concentrations of insulin, IGF-I, and IGFBPs for a total of 513 incident breast cancer cases and 987 matched controls. RESULTS: Globally, risk was unassociated with levels of IGF-I, IGFBP-3, or IGF-I adjusted for IGFBP-3. When breaking down the analysis by subgroups of age at blood donation, an increase in risk was observed for increasing levels of IGF-I in women aged 55 or older, in the Umeå cohort only (odds ratios of 1.00, 1.73, 1.76, 1.90; Ptrend = 0.05). This effect weakened, however, when the analysis was restricted to subjects who did not use exogenous hormones for the treatment of menopausal symptoms. Levels of IGF-I and IGFBP-3 were not related to risk in younger women, recruited before age 50, contrary to observations from previous studies. In a subcohort where blood samples had been collected after at least four hours of fasting, breast cancer risk showed no clear associations with levels of insulin, IGFBP-1, or IGFBP-2. CONCLUSIONS: Our results do not confirm earlier findings of an association of plasma IGF-I levels with breast cancer risk especially in young women, but suggest a possible association with postmenopausal breast cancer risk, possibly among ERT/HRT users only. Our results do not support the hypothesis that elevated plasma insulin levels, and reduced levels of IGFBP-I and IGFBP-2, are associated with increased breast cancer risk.

Adult↗

PubMed2002

Invitation to a population-based cohort study: differences between subjects recruited using various strategies.

AIM: The present study compares subjects recruited to a population-based prospective cohort study by community versus personal invitation, and subjects responding late versus early to personal invitation. Subjects were compared with respect to sociodemographic characteristics, selected lifestyle factors, cancer incidence and mortality. METHODS: The Malmö Diet and Cancer Study recruited a total of 28,098 subjects between 1991 and 1996. Entire birth-year cohorts, born 1923-50, were recruited using community directed (passive) invitation, and a personal letter of invitation (active recruitment). Information on sociodemography and lifestyle was obtained using a self-administered questionnaire. Anthropometric measurements were assessed at a physical examination. Cancer incidence and cause of death were retrieved using record linkage with national registries. RESULTS: Subjects responding to community directed invitation were older, and more often females, than participants recruited using personal invitation. Furthermore, participants recruited through passive invitation had a comparably more favourable situation with regard to sociodemographic and lifestyle factors. They also had a lower frequency of prevalent disease, lower incidence of cancer and lower mortality. Contrary to this, men were more likely to respond late to a personal letter of invitation and late responders were also older, as compared with subjects responding early to personal invitation. Furthermore, those who responded late had a comparatively unfavourable socioeconomic situation and were characterized by a high prevalence of current smoking, obesity, weight change, and prevalent disease. CONCLUSIONS: Subjects who are recruited using different strategies in population-based cohort studies may have different sociodemographic and lifestyle characteristics, and may vary with regard to prevalent disease, cancer incidence and subsequent mortality.

Adult↗

PubMed2002

Incidence of cardiovascular disease, cancer and death in postmenopausal women affirming use of hormone replacement therapy.

AIM: The goal of this study was to evaluate the incidence of myocardial infarction, cancer and death in relation to use of hormone replacement therapy (HRT). METHODS: Nine years' follow up of an urban cohort of peri-/postmenopausal women was undertaken. Local and national registers were used for retrieval of events. RESULTS: The incidence of myocardial infarction per 1.000 person-years in users and non-users was 0.61 (5/962) and 2.20 (92/4759) respectively, adjusted relative risk (RR) 0.37; 95% confidence interval 0.15-0.90. Rates of mortality from cardiovascular disease and cancer were 0.36 and 1.10, p= 0.058, and 2.60 and 2.09, p=0.360 respectively. In terms of all-cause mortality the adjusted RR was 1.02; 0.69-1.52, incidence of cancer 1.28; 1.01-1.64, breast cancer 1.52; 1.01-2.28 and endometrial cancer 3.61; 1.54-8.46. CONCLUSIONS: Women affirming use of HRT had a lower incidence of myocardial infarction. Further studies are needed to assess whether the absence of effect on total mortality may be accounted for by an increased cancer risk.

Adult↗

PubMedDate not supplied

Risk of myocardial infarction in relation to plasma levels of homocysteine and inflammation-sensitive proteins: a long-term nested case-control study.

Several studies have found that the homocysteine plasma level is associated with cardiovascular disease. The authors previously described a relationship between concentrations of fibrinogen and other inflammation-sensitive plasma proteins, namely, alpha1-antitrypsin, ceruloplasmin, haptoglobin, and orosomucoid (alpha1-acid glucoprotein) and the incidence of myocardial infarction (MI). Whether levels of these proteins are related to homocysteine has not been clarified. The aim of this study was to investigate whether a supposed relationship between homocysteine in plasma and the occurrence of MI is modified by these inflammation-sensitive proteins. A nested case-control study was designed, comprising 241 cases of MI, with a mean age of 48 years at baseline, and 241 controls matched for age, month of examination, and duration of follow-up. The mean homocysteine concentration did not differ between cases and controls and there was no association between the baseline homocysteine level and the time lapse before the occurrence of the MI. For the cases, there was no correlation between homocysteine and any of the measured proteins, but for the controls, homocysteine was weakly but significantly negatively correlated to haptoglobin and ceruloplasmin and slightly positively correlated to albumin. For the separated groups of cases and controls there was no association between the number of inflammation-sensitive proteins in the top quartiles and homocysteine concentration. In this population-based, prospective cohort study the occurrence of MI had no relationship to homocysteine baseline plasma level. Furthermore, there was no strong association between homocysteine and the concentrations of any of these inflammation-sensitive proteins.

Blood Proteins↗

PubMedDate not supplied

Incidence of myocardial infarction and death in relation to walking-induced calf pain and plasma levels of inflammation-sensitive proteins.

Walking-induced calf pain as well as levels of different inflammation-sensitive plasma proteins (ISPs) are related to cardiovascular disease (CVD). This prospective cohort study explored the relationship between ISPs and walking-related calf pain and the interrelationships between ISPs and calf pain in the prediction of death and incidence of coronary events (CE). In 5,725 apparently healthy men, 46 +/-3.0 years old, plasma concentrations of orosomucoid (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. Walking-induced calf pain was assessed by questionnaire. Mortality and incidence of CE were monitored over a mean follow-up of 18 years in subjects defined by the presence of calf pain and ISP level (0 to 1 or 2 to 5 ISP(s) in the top quartile). The prevalence of calf pain (7.3%) was significantly related to age, lifestyle, and traditional risk factors of CVD and ISP levels. The risk factor-adjusted relative risks for CE, CVD- and all-cause mortality were 1.89 (CI: 1.27 to 2.82), 2.90 (CI: 1.82 to 4.62), and 2.67 (CI: 1.97 to 3.57), respectively, for men with calf pain and high ISP levels (reference: no calf pain and low ISP levels). The corresponding risk for those with calf pain and low ISP levels were 1.34 (CI: 0.91 to 1.97), 1.47 (CI: 0.90 to 2.41), and 1.31 (CI: 0.95 to 1.81), respectively. These results indicate, on the one hand, that walking-induced calf pain is associated with high ISP levels and, on the other, that the risk of CVD in men with calf pain is substantially higher in those with high ISP levels than in those with low levels.

Adult↗