To study associations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in maternal circulation with the risk of preeclampsia with and without fetal growth restriction.
Nested case-control study.
A cohort of 29 948 pregnant women in Norway.
Cases were identified through linkage to the Medical Birth Registry of Norway. We selected 69 preterm and 36 term preeclampsia cases with delivery of a small-for-gestational-age (SGA) infant, 83 preterm and 154 term preeclampsia cases without SGA delivery, and 384 normotensive controls.
We measured PlGF and sFlt-1 in maternal serum samples from each trimester.
Odds ratios of preeclampsia subtypes by tertile categories of PlGF and sFlt-1.
Low (lowest third) PlGF and sFlt-1 levels in the first trimester, and low (lowest third) increase in PlGF and strong (highest third) increase in sFlt-1 from first to second trimester were associated with increased risk of preterm preeclampsia, both with and without SGA offspring. For term preeclampsia with SGA offspring, the associations were similar to the findings for preterm preeclampsia. For term preeclampsia without SGA offspring, low increase in PlGF from first to second trimester and high sFlt-1 in the third trimester were associated with increased risk.
Low PlGF and high sFlt-1 levels in maternal circulation are associated with subsequent development of preeclampsia, regardless of whether fetal growth is affected or not. For term preeclampsia without fetal growth restriction, the imbalance in angiogenic factors seems to appear later in pregnancy than for preterm preeclampsia.
Adult height and body weight are positively associated with breast cancer risk after menopause, but few studies have investigated these factors according to molecular breast cancer subtype. A total of 18,562 postmenopausal Norwegian women who were born between 1886 and 1928 were followed up for breast cancer incidence from the time (between 1963 and 1975) height and weight were measured until 2008. Immunohistochemical and in situ hybridization techniques were used to subtype 734 incident breast cancer cases into Luminal A, Luminal B [human epidermal growth factor receptor 2 (HER2-)], Luminal B (HER2+), HER2 subtype, basal-like phenotype (BP) and five-negative phenotype (5NP). We used Cox regression analysis to assess adult height and body mass index (BMI) in relation to risk of these subtypes. We found a positive association of height with risk of Luminal A breast cancer (ptrend , 0.004), but there was no clear association of height with any other subtype. BMI was positively associated with risk of all luminal breast cancer subtypes, including Luminal A (ptrend , 0.002), Luminal B (HER2-) (ptrend , 0.02), Luminal B (HER2+) (ptrend , 0.06), and also for the HER2 subtype (ptrend , 0.04), but BMI was not associated with risk of the BP or 5NP subtypes. Nonetheless, statistical tests for heterogeneity did not provide evidence that associations of height and BMI differed across breast cancer subtypes. This study of breast cancer risk among postmenopausal women suggests that height is positively associated with risk of Luminal A breast cancer. BMI is positively associated with risk of all luminal subtypes and for the HER2 subtype.
Recent studies have suggested that the association of low thyroid function with high body mass is restricted to nonsmokers.
The aim was to study the association of thyroid function with body mass separately for smokers and never-smokers.
We conducted a cross-sectional, population-based study.
We studied 27,097 individuals older than 40 yr of age who were without previously known thyroid disease.
We measured mean body mass index (BMI) and odds ratio for obesity (BMI > or = 30.0 kg/m(2)) according to categories of thyroid function, in women and men, and separately for current smokers and never-smokers. We also studied the association with BMI within the reference range of TSH (0.50-3.5 mU/liter).
TSH within the reference range was positively associated with BMI (P for trend
Reproductive factors that have a well-documented effect on breast cancer risk may also influence the prognosis of the disease, but previous studies on breast cancer survival have yielded conflicting results. We combined information from two population-based registries and obtained information on 16,970 parous women with invasive breast cancer. Cox regression analysis was used to assess breast cancer survival in relation to age at diagnosis, age at first birth, time since last birth and parity. We stratified the analyses by age at diagnosis (
Studies on birth size characteristics and adult risk for prostate cancer have been few and inconclusive. We prospectively examined the association between birth size and risk for prostate cancer with particular emphasis on metastatic disease. A total of 19,681 singleton males born between 1920 and 1958, whose birth records were kept at St. Olav's University Hospital (Trondheim, Norway), were followed up for prostate cancer by linkage to the Norwegian Cancer Registry. A total of 159 cases of prostate cancer were diagnosed during follow-up; 33 had metastases at diagnosis. Overall, there was little evidence for any association between birth size and prostate cancer risk; however, there was a positive association for birth size and metastatic disease. Men in the highest quartile of birth length (> or =53 cm) had a relative risk of 2.5 (95% CI 1.0-6.3) compared to men in the lowest quartile (
Small birth size may be associated with increased risk of cardiovascular diseases (CVD), whereas large birth size may predict increased risk of obesity and some cancers. The net effect of birth size on long-term mortality has only been assessed in individual studies, with conflicting results.
The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines for conducting and reporting meta-analysis of observational studies were followed. We retrieved 22 studies that assessed the association between birthweight and adult mortality from all causes, CVD or cancer. The studies were systematically reviewed and those reporting hazard ratios (HRs) and 95% confidence intervals (95% CIs) per kilogram (kg) increase in birthweight were included in generic inverse variance meta-analyses.
For all-cause mortality, 36,834 deaths were included and the results showed a 6% lower risk (adjusted HR?=?0.94, 95% CI: 0.92-0.97) per kg higher birthweight for men and women combined. For cardiovascular mortality, the corresponding inverse association was stronger (HR?=?0.88, 95% CI: 0.85-0.91). For cancer mortality, HR per kg higher birthweight was 1.13 (95% CI: 1.07-1.19) for men and 1.04 (95% CI: 0.98-1.10) for women (P(interaction)?=?0.03). Residual confounding could not be eliminated, but is unlikely to account for the main findings.
These results show an inverse but moderate association of birthweight with adult mortality from all-causes and a stronger inverse association with cardiovascular mortality. For men, higher birthweight was strongly associated with increased risk of cancer deaths. The findings suggest that birthweight can be a useful indicator of processes that influence long-term health.
To assess the association of pre-eclampsia with later cardiovascular death in mothers according to their lifetime number of pregnancies, and particularly after only one child.
Prospective, population based cohort study.
Medical Birth Registry of Norway.
We followed 836,147 Norwegian women with a first singleton birth between 1967 and 2002 for cardiovascular mortality through linkage to the national Cause of Death Registry. About 23,000 women died by 2009, of whom 3891 died from cardiovascular causes. Associations between pre-eclampsia and cardiovascular death were assessed by hazard ratios, estimated by Cox regression analyses. Hazard ratios were adjusted for maternal education (three categories), maternal age at first birth, and year of first birth
The rate of cardiovascular mortality among women with preterm pre-eclampsia was 9.2% after having only one child, falling to 1.1% for those with two or more children. With term pre-eclampsia, the rates were 2.8% and 1.1%, respectively. Women with pre-eclampsia in their first pregnancy had higher rates of cardiovascular death than those who did not have the condition at first birth (adjusted hazard ratio 1.6 (95% confidence interval 1.4 to 2.0) after term pre-eclampsia; 3.7 (2.7 to 4.8) after preterm pre-eclampsia). Among women with only one lifetime pregnancy, the increase in risk of cardiovascular death was higher than for those with two or more children (3.4 (2.6 to 4.6) after term pre-eclampsia; 9.4 (6.5 to 13.7) after preterm pre-eclampsia). The risk of cardiovascular death was only moderately elevated among women with pre-eclamptic first pregnancies who went on to have additional children (1.5 (1.2 to 2.0) after term pre-eclampsia; 2.4 (1.5 to 3.9) after preterm pre-eclampsia). There was little evidence of additional risk after recurrent pre-eclampsia. All cause mortality for women with two or more lifetime births, who had pre-eclampsia in first pregnancy, was not elevated, even with preterm pre-eclampsia in first pregnancy (1.1 (0.87 to 1.14)).
Cardiovascular death in women with pre-eclampsia in their first pregnancy is concentrated mainly in women with no additional births. This association might be due to health problems that discourage or prevent further pregnancies rather than to pre-eclampsia itself. As a screening criterion for cardiovascular disease risk, pre-eclampsia is a strong predictor primarily among women with only one child-particularly with preterm pre-eclampsia.
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To compare associations of conventional risk factors with cardiovascular death within couples and in the population as a whole.
We analysed baseline data (1995-97) from the HUNT2 Study in Norway linked to the national Causes of Death Registry. We compared risk within couples using stratified Cox regression.
During 914776 person-years, 3964 cardiovascular deaths occurred, and 1658 of the deaths occurred among 1494 couples. There were consistently stronger associations of serum lipids and blood pressure with cardiovascular mortality within couples compared to the population as a whole. For instance, for systolic blood pressure (per 20mmHg), the hazard ratio (HR) within couples was 1.28 (95% confidence interval: 1.17, 1.40) compared to 1.16 (1.12, 1.20) in the total population, and for diastolic pressure (per 10mmHg), the corresponding HRs were 1.16 (1.07, 1.26) and 1.11 (1.08, 1.13). Anthropometric factors (BMI, waist circumference, waist-hip ratio) as well as diabetes, smoking, physical activity, and education, showed nearly identical positive associations within couples and in the total population.
Prospective population studies may tend to slightly underestimate associations of these factors with cardiovascular mortality.
The aim of this study was to determine whether blood pressure, body mass index (BMI), serum lipids, glucose, and renal function are associated with left ventricular (LV) and right ventricular function in a low-risk population.
The associations of common risk factors with cardiac function were assessed, using multiple linear regression, in a random sample of 1,266 individuals free from hypertension, diabetes, and cardiovascular disease. A combination of conventional echocardiographic, speckle-tracking, and tissue Doppler methods was used to assess cardiac function.
Older age and higher BMI, systolic and diastolic blood pressure, and non-high-density lipoprotein (HDL) cholesterol were associated with lower LV function. Thus, LV strain was reduced by approximately 5% per 5 kg/m(2) increase in BMI and by 4% per 10 mm Hg increase in diastolic blood pressure. Corresponding reductions in peak early diastolic mitral annular velocity were 7% for both BMI and diastolic blood pressure. Higher HDL cholesterol was associated with better LV function. In women, smoking was also associated with reduced LV function. LV function was lower also at low levels of diastolic pressure and BMI. Reduced right ventricular function was related to older age, smoking, higher diastolic blood pressure and non-HDL cholesterol, and lower HDL cholesterol.
These findings suggest that conventional risk factors may predict cardiac function many years before clinical disease. The J-shaped associations related to diastolic blood pressure and BMI may suggest that in some individuals, low levels of these factors may indicate underlying but unknown disease.