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Background: High dietary intake or blood concentrations (as biomarkers of dietary intake) of vitamin C, carotenoids, and vitamin E have been associated with reduced risk of cardiovascular disease, cancer, and mortality, but these associations have not been systematically assessed., Objective: We conducted a systematic review and meta-analysis of prospective studies of dietary intake and blood concentrations of vitamin C, carotenoids, and vitamin E in relation to these outcomes., Design: We searched PubMed and Embase up to 14 February 2018. Summary RRs and 95% CIs were calculated with the use of random-effects models., Results: Sixty-nine prospective studies (99 publications) were included. The summary RR per 100-mg/d increment of dietary vitamin C intake was 0.88 (95% CI: 0.79, 0.98, I2 = 65%, n = 11) for coronary heart disease, 0.92 (95% CI: 0.87, 0.98, I2 = 68%, n = 12) for stroke, 0.89 (95% CI: 0.85, 0.94, I2 = 27%, n = 10) for cardiovascular disease, 0.93 (95% CI: 0.87, 0.99, I2 = 46%, n = 8) for total cancer, and 0.89 (95% CI: 0.85, 0.94, I2 = 80%, n = 14) for all-cause mortality. Corresponding RRs per 50-μmol/L increase in blood concentrations of vitamin C were 0.74 (95% CI: 0.65, 0.83, I2 = 0%, n = 4), 0.70 (95% CI: 0.61, 0.81, I2 = 0%, n = 4), 0.76 (95% CI: 0.65, 0.87, I2 = 56%, n = 6), 0.74 (95% CI: 0.66, 0.82, I2 = 0%, n = 5), and 0.72 (95% CI: 0.66, 0.79, I2 = 0%, n = 8). Dietary intake and/or blood concentrations of carotenoids (total, β-carotene, α-carotene, β-cryptoxanthin, lycopene) and α-tocopherol, but not dietary vitamin E, were similarly inversely associated with coronary heart disease, stroke, cardiovascular disease, cancer, and/or all-cause mortality., Conclusions: Higher dietary intake and/or blood concentrations of vitamin C, carotenoids, and α-tocopherol (as markers of fruit and vegetable intake) were associated with reduced risk of cardiovascular disease, total cancer, and all-cause mortality. These results support recommendations to increase fruit and vegetable intake, but not antioxidant supplement use, for chronic disease prevention.

Background: We hypothesized that circulating markers reflecting monocyte/macrophage and T cell activation are associated with increased risk of myocardial infarction (MI) in apparently healthy individuals., Methods: Serum monocyte/macrophage and T cell activation markers soluble (s) CD163, sCD14, Gal3BP, sCD25 and sCD166 were analyzed by enzyme-immunoassay in a case-control study nested within the population-based HUNT2 cohort in Norway. Among 58,761 apparently healthy men and women followed a median 11.3years, 1587 incident MI cases were registered, and compared to 3959 age- and sex-matched controls., Results: Higher serum sCD163 (Q4 vs. Q1 OR: 1.27, P-trend 0.002), sCD14 (Q4 vs. Q1 OR: 1.38, P-trend<0.001), and especially sCD25 (Q4 vs. Q1 OR: 1.45, P-trend<0.001), were associated with increased MI risk in the age-and sex adjusted models. However, after additional adjustment for cardiovascular risk factors these associations were strongly attenuated (Q4 vs Q1 ORs between 1.02 and 1.12, P-trends between 0.30 and 0.58)., Conclusions: sCD163, sCD14 and sCD25 may reflect leukocyte activation and inflammatory mechanisms related to atherogenesis, but do not predict MI risk above and beyond conventional cardiovascular risk factors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aim: Epidemiological studies have reported increased risk of cardiovascular disease, cancer and all-cause mortality with greater resting heart rate, however, the evidence is not consistent. Differences by gender, adjustment for confounding factors, as well as the potential impact of subclinical disease are not clear. A previous meta-analysis missed a large number of studies, and data for atrial fibrillation have not been summarized before. We therefore aimed to clarify these associations in a systematic review and meta-analysis of prospective studies., Methods and Results: PubMed and Embase were searched up to 29 March 2017. Summary RRs and 95% confidence intervals (CIs) were calculated using random effects models. Eighty seven studies were included. The summary RR per 10 beats per minute increase in resting heart rate was 1.07 (95% CI: 1.05-1.10, I 2  = 61.9%, n = 31) for coronary heart disease, 1.09 (95% CI: 1.00-1.18, I 2  = 62.3%, n = 5) for sudden cardiac death, 1.18 (95% CI: 1.10-1.27, I 2  = 74.5%, n = 8) for heart failure, 0.97 (95% CI: 0.92-1.02, I 2  = 91.4%, n = 9) for atrial fibrillation, 1.06 (95% CI: 1.02-1.10, I 2  = 59.5%, n = 16) for total stroke, 1.15 (95% CI: 1.11-1.18, I 2  = 84.3%, n = 35) for cardiovascular disease, 1.14 (95% CI: 1.06-1.23, I 2  = 90.2%, n = 12) for total cancer, and 1.17 (95% CI: 1.14-1.19, I 2  = 94.0%, n = 48) for all-cause mortality. There was a positive dose-response relationship for all outcomes except for atrial fibrillation for which there was a J-shaped association., Conclusion: This meta-analysis found an increased risk of coronary heart disease, sudden cardiac death, heart failure, atrial fibrillation, stroke, cardiovascular disease, total cancer and all-cause mortality with greater resting heart rate., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: To compare associations of conventional risk factors with cardiovascular death within couples and in the population as a whole., Methods: 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., Results: 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., Conclusions: Prospective population studies may tend to slightly underestimate associations of these factors with cardiovascular mortality., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: We analyzed the association between light-to-moderate alcohol intake and the risk of heart failure (HF)., Methods and Results: We studied 60,665 individuals free of HF who provided information on alcohol consumption in a population-based cohort study conducted in 1995-97 in Norway. Sociodemographic factors, cardiovascular risk factors and common chronic disorders were assessed by questionnaires and/or by a clinical examination. The cohort was followed for a first HF event for an average of 11.2 ± 3.0 years. Mean alcohol consumption was 2.95 ± 4.5 g/day; 1588 HF cases occurred during follow-up. The quantity of alcohol consumption was inversely associated with incident HF in this low-drinking population. The risk was lowest for consumption over three but less than six drinks/week; the multivariate hazard ratio when comparing this category to non-drinkers was 0.67 (95% CI: 0.50-0.92). Among problem drinkers based on CAGE questionnaires, total consumption showed no favorable association with HF, even when overall consumption was otherwise moderate. Excluding former drinkers and controlling for common chronic diseases had minimal effect on these associations. Frequent alcohol consumption, i.e. more than five times/month, was associated with the lowest HF risk; the adjusted hazard ratio comparing this group to alcohol intake less than once/month was 0.83 (95% CI: 0.68-1.03). We found no evidence for a differential effect according to beverage type, nor that the competing risks of death from other causes modified the association., Conclusions: Frequent light-to-moderate alcohol consumption without problem drinking was associated with a lower HF risk in this population characterized by a low average alcohol intake., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Aims: CXCL16 is an interferon-γ-regulated chemokine and scavenger receptor for oxidized low-density lipoprotein that is expressed in atherosclerotic lesions. High soluble CXCL16 levels during acute cardiovascular events may indicate impaired long-term prognosis, but it is not known if CXCL16 is associated with the risk of developing cardiovascular disease in healthy individuals. We aimed to assess whether soluble CXCL16 is associated with risk of myocardial infarction (MI) in a nested case-control study within a large population-based cohort., Methods: We conducted a case-control study nested within the population-based HUNT2 cohort in Norway. A total of 58,761 men and women free of known cardiovascular disease were followed for a first myocardial infarction (MI), and during 11.3 years of follow-up, 1587 incident MIs were registered. These cases were compared to 3959 age- and sex-matched controls., Results: Among MI cases, the median CXCL16 concentration was 9.9 ng/ml (interquartile range 7.2-12.6) compared to 9.6 ng/ml (interquartile range 6.9-12.3) among controls (p < 0.001). Although the difference in median value between cases and controls was small, MI risk was twice as high (OR, 2.08; 95% CI: 1.74-2.50) among participants in the highest quartile compared to participants in the lowest quartile of CXCL16 after adjustment for age and sex. Additional adjustment for serum lipids, body mass index, smoking habits, diabetes mellitus, serum creatinine, and high-sensitivity C-reactive protein attenuated the excess risk by about half, yielding an odds ratio of 1.46 (95% CI: 1.19-1.79)., Conclusion: Soluble CXCL16 may provide novel information in clinical cardiovascular risk assessment, but its importance needs to be verified in other prospective population studies., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: High resting heart rate has been associated with increased risk of type 2 diabetes in several studies, but the available data are not consistent and it is unclear if there is a dose-response relationship between resting heart rate and type 2 diabetes risk. We aimed to clarify this association by conducting a systematic review and meta-analysis of published studies., Methods and Results: PubMed, Embase and Ovid Medline databases were searched for prospective studies published up until October 11th, 2013. Summary relative risks were estimated using a random effects model. Ten cohort studies with >5628 cases and 119,915 participants were included. The summary RR for high vs. low resting heart rate was 1.83 (95% CI: 1.28-2.60, I(2) = 88%, n = 7), and in the dose-response analysis the summary RR was 1.20 (95% CI: 1.07-1.34, I(2) = 93%, n = 9) for an increase of 10 beats per minute. The heterogeneity was to a large degree explained by two studies. There was evidence of nonlinear associations between resting heart rate (pnonlinearity < 0.0001) and risk of type 2 diabetes., Conclusion: The current meta-analysis indicates a strong positive association between high resting heart rate and the risk of type 2 diabetes. As a non-invasive marker of type 2 diabetes risk, resting heart rate may have potential in the clinical setting, especially for interventions aimed at lowering the risk of type 2 diabetes. Additional studies are needed to clarify the mechanisms that may be responsible for the assoiation between resting heart rate and type 2 diabetes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Enhanced generation of reactive oxygen species and increased oxidative-induced DNA damage have been identified as possible contributors to atherosclerosis. The base excision repair (BER) pathway is the principal mechanism by which mammalian cells repair oxidative DNA damage. BER deficiency can potentially accelerate atherogenesis., Methods: We evaluated the association of Single Nucleotide Polymorphisms (SNPs) in genes encoding four different BER proteins (NEIL3, OGG1, APEX1 and XRCC1) with the incidence of myocardial infarction in a nested case-control study among participants of the second survey of the HUNT Study. The study population included 1624 cases and 4087 age- and sex-matched controls., Results: For the NEIL3 SNP rs12645561, the TT genotype was associated with increased risk of MI (OR 1.47, 95% CI 1.02-2.12, p uncorrected for multiple comparisons = 0.04) both in the genotypic test (compared to the CC genotype) and in the recessive genetic model (compared to the CC and CT genotypes combined). For the other two NEIL3 SNPs (rs10013040 and rs1395479) and for the SNPs of OGG1 (rs1052133), APEX1 (rs1878703) and XRCC1 (rs25489) we observed no association with risk of myocardial infarction., Conclusion: We found that the NEIL3 rs12645561 SNP TT genotype was associated with increased risk of myocardial infarction. If confirmed in other studies, this association may suggest a possible role of attenuated DNA repair, and NEIL3 in particular, in atherogenesis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Dairy product and calcium intakes have been associated with increased prostate cancer risk, but whether specific dairy products or calcium sources are associated with risk is unclear., Objective: In the Continuous Update Project, we conducted a meta-analysis of prospective studies on intakes of dairy products and calcium and prostate cancer risk., Design: PubMed and several other databases were searched up to April 2013. Summary RRs were estimated by using a random-effects model., Results: Thirty-two studies were included. Intakes of total dairy products [summary RR: 1.07 (95% CI: 1.02, 1.12; n = 15) per 400 g/d], total milk [summary RR: 1.03 (95% CI: 1.00, 1.07; n = 14) per 200 g/d], low-fat milk [summary RR: 1.06 (95% CI: 1.01, 1.11; n = 6) per 200 g/d], cheese [summary RR: 1.09 (95% CI: 1.02, 1.18; n = 11) per 50 g/d], and dietary calcium [summary RR: 1.05 (95% CI: 1.02, 1.09; n = 15) per 400 mg/d] were associated with increased total prostate cancer risk. Total calcium and dairy calcium intakes, but not nondairy calcium or supplemental calcium intakes, were also positively associated with total prostate cancer risk. Supplemental calcium was associated with increased risk of fatal prostate cancer., Conclusions: High intakes of dairy products, milk, low-fat milk, cheese, and total, dietary, and dairy calcium, but not supplemental or nondairy calcium, may increase total prostate cancer risk. The diverging results for types of dairy products and sources of calcium suggest that other components of dairy rather than fat and calcium may increase prostate cancer risk. Any additional studies should report detailed results for subtypes of prostate cancer., (© 2015 American Society for Nutrition.)

Objective: Women with a history of preeclampsia are at increased lifetime risk for cardiovascular disease. Their offspring may carry similar risks. The aim was to study cardiovascular and metabolic risk factors 11 years after the delivery among women who were diagnosed with mild, moderate, or severe preeclampsia, and their offspring, compared with women without preeclampsia and their offspring., Study Design: In a follow-up 11 years after a nested case-control study at birth, we studied 611 mother-offspring dyads, including 228 dyads with preeclampsia in the index pregnancy and 383 dyads without preeclampsia. Cardiovascular and metabolic risk profiles were assessed by serum lipids (total cholesterol, high-density lipoprotein [HDL] cholesterol, non-HDL cholesterol), insulin-related factors (glucose, insulin, and homeostasis assessment model for insulin resistance) and blood pressure in mothers and children., Results: Among mothers with mild or moderate preeclampsia, levels of glucose, insulin, and homeostasis assessment model for insulin resistance were higher than in the nonpreeclampsia group and also higher compared with mothers with severe preeclampsia (all P < .05). HDL cholesterol was lower in mothers with mild or moderate preeclampsia (all P < .05), but other lipids did not substantially differ between the groups. Body mass index and blood pressure (systolic and diastolic) were also higher in the mild and moderate preeclampsia group compared with mothers without preeclampsia (all P < .05). Among the offspring, we found no clear differences in any blood analytes between the groups., Conclusion: Women with a previous diagnosis of mild or moderate, but not severe, preeclampsia may have an adverse metabolic and cardiovascular risk profile 11 years after the delivery., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Aims: Breastfeeding has been associated with reduced risk of maternal type 2 diabetes in some cohort studies, but the evidence from published studies have differed with regard to the strength of the association. To clarify this association we conducted a systematic review and dose-response meta-analysis of breastfeeding and maternal risk of type 2 diabetes., Methods and Results: We conducted a systematic review and dose-response meta-analysis of prospective studies of breastfeeding and maternal risk of type 2 diabetes. We searched the PubMed, Embase and Ovid databases up to September 19th 2013. Summary relative risks were estimated using a random effects model. Six cohort studies including 10,842 cases among 273,961 participants were included in the meta-analysis. The summary RR for the highest duration of breastfeeding vs. the lowest was 0.68 (95% CI: 0.57-0.82, I(2) = 75%, p heterogeneity = 0.001, n = 6). The summary RR for a three month increase in the duration of breastfeeding per child was 0.89 (95% CI: 0.77-1.04, I(2) = 93%, p heterogeneity < 0.0001, n = 3) and the summary RR for a one year increase in the total duration of breastfeeding was 0.91 (95% CI: 0.86-0.96, I(2) = 81%, p heterogeneity = 0.001, n = 4). There was little difference in the summary estimates whether or not BMI had been adjusted for. The inverse associations appeared to be nonlinear, p nonlinearity < 0.0001 for both analyses, and in both analyses the reduction in risk was steeper when increasing breastfeeding from low levels., Conclusion: This meta-analysis suggests that there is a statistically significant inverse association between breastfeeding and maternal risk of type 2 diabetes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: Placental weight has been associated with mammographic pattern and coronary heart disease in the adult offspring, but the mechanisms are unknown. We evaluated the associations of maternal and cord blood hormones with placental weight in normal pregnancies., Methods: Prospective study of 167 normal singleton pregnancies in Boston, USA and 256 in Shanghai, China. Maternal hormone levels at the 27th gestational week were available for all pregnancies. Cord blood measurements were available for 86 pregnancies in Boston and 104 in Shanghai. Pearson partial correlation coefficients of log-transformed hormone levels with placental weight were calculated., Results: Maternal levels of estriol, testosterone, and progesterone (P < .05) were positively associated with placental weight. There was no such evidence for adiponectin, prolactin, and insulin-like growth factor (IGF)-I. Cord blood steroids tended to be inversely associated with placental weight, the results being statistically significant for testosterone (P < .05). There was a marginally significant positive association of cord blood IGF-I with placental weight. Reported results were adjusted for study center., Conclusions: Placental weight appears to be positively correlated with maternal steroids. Its correlation with cord blood steroids, however, appears inverse, compatible with negative feedback mechanisms. There is also a suggestion for placental weight to be positively associated with cord blood IGF-I., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The association between intake of dairy products and the risk of type 2 diabetes has been investigated in several studies, but the evidence is not conclusive., Objective: We conducted an updated systematic review and dose-response meta-analysis of dairy product intake and the risk of type 2 diabetes., Design: We searched the PubMed database for prospective cohort and nested case-control studies of dairy product intake and risk of type 2 diabetes up to 5 June 2013. Summary RRs were estimated by use of a random-effects model., Results: Seventeen cohort studies were included in the meta-analysis. In the dose-response analysis, the summary RRs (95% CIs) were 0.93 (0.87, 0.99; I(2) = 33%) per 400 g total dairy products/d (n = 12), 0.98 (0.94, 1.03; I(2) = 8%) per 200 g high-fat dairy products/d (n = 9), 0.91 (0.86, 0.96; I(2) = 40%) per 200 g low-fat dairy products/d (n = 9), 0.87 (0.72, 1.04; I(2) = 94%) per 200 g milk/d (n = 7), 0.92 (0.86, 0.99; I(2) = 0%) per 50 g cheese/d (n = 8), and 0.78 (0.60, 1.02; I(2) = 70%) per 200 g yogurt/d (n = 7). Nonlinear inverse associations were observed for total dairy products (P-nonlinearity < 0.0001), low-fat dairy products (P-nonlinearity = 0.06), cheese (P-nonlinearity = 0.05), and yogurt (P-nonlinearity = 0.004), and there was a flattening of the curve at higher intakes., Conclusions: This meta-analysis suggests that there is a significant inverse association between intakes of dairy products, low-fat dairy products, and cheese and risk of type 2 diabetes. Any additional studies should assess the association between other specific types of dairy products and the risk of type 2 diabetes and adjust for more confounding factors.

Objective: To study the association of prepregnancy blood pressure, lipids, and glucose with length of pregnancy, and to assess whether the association between preterm delivery and later maternal cardiovascular disease may be due to common risk factors., Study Design: Prospective study linking information of 3506 women in the HUNT Study with 4990 singleton births recorded in the Medical Birth Registry of Norway., Results: Unfavorable prepregnancy levels of triglycerides, cholesterol, high-density lipoprotein-cholesterol, and glucose were associated with increased risk of preterm birth and shorter gestational length. Triglycerides above 1.6 mmol/L were associated with 60% higher risk of preterm birth (odds ratio, 1.6, 95% confidence interval, 1.0-2.5), compared with triglycerides below 0.7 mmol/L. Blood pressure was positively associated with risk of preterm birth and shorter gestational length, but these associations were substantially attenuated after adjustment for hypertensive disorders in pregnancy., Conclusion: Women with unfavorable cardiovascular risk factors before conception have excess risk of preterm birth., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Purpose: It has been suggested that paternal genes may contribute to the risk of maternal hypertensive disorders in pregnancy and that genes associated with cardiovascular disease could be involved in the etiology of maternal hypertensive disorders in pregnancy. If these genes are of fetal origin, one would expect that paternal cardiovascular risk factors are associated with the fathering of pregnancies in which the mothers experience hypertensive disorders. Thus, we have studied 14,130 offspring and parents in Norway (1967-1997) to assess whether the fathering of pregnancies complicated by hypertensive disorders in the mother is associated with paternal cardiovascular risk factors., Methods: In a population-based study of 14,130 family units, data on parental cardiovascular risk factors (blood pressure, body mass index, waist circumference, nonfasting serum lipids and glucose) collected in the Norwegian Hunt Study (1995-1997) were linked to pregnancy data from the Medical Birth Registry of Norway (1967-1997). Multiple linear regression methods were used, and all analyses were adjusted for lifestyle factors likely to be shared by the parents., Results: There was no association between hypertensive disorders in pregnancy and paternal cardiovascular risk factors., Conclusions: We found no evidence that the fathering of pregnancies complicated by hypertensive disorders in the mother is associated with an unfavorable paternal cardiovascular risk profile., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Placental weight and infant birthweight may be markers of different types of preeclampsia. We studied birthweight within placental weight percentiles in pregnancies with and without preeclampsia., Study Design: This was a population study of 317,688 singleton births., Results: Within the lowest 10% of placental weight, 36% of the offspring were small for gestational age (SGA) in preeclamptic pregnancies and 14% in normotensive pregnancies (relative risk, 2.6; 95% confidence interval, 2.4-2.8). Risk of SGA subsided with increasing placental weight and was negligible at >50th percentile. At low placental weights, large for gestational age (LGA) offspring were nearly nonexistent; however, at >70th percentile, LGA occurred more often in pregnancies with preeclampsia. Within the highest 10% of placental weight, 20.7% of the infants were LGA in the preeclampsia group, and 15.3% of the infants were LGA in pregnancies without preeclampsia (relative risk, 1.4; 95% confidence interval, 1.2-1.5)., Conclusion: In pregnancies with small placentas, the offspring were more often SGA in preeclamptic pregnancies and more often LGA at high placental weights. The results support the hypothesis that preeclampsia may represent different diseases, depending on placental size and infant birthweight.

Background: Research suggests that singleton births following assisted fertilisation are associated with adverse outcomes; however, these results might be confounded by factors that affect both fertility and pregnancy outcome. We therefore compared pregnancy outcomes in women who had singleton pregnancies conceived both spontaneously and after assisted fertilisation., Methods: In a population-based cohort study, we assessed differences in birthweight, gestational age, and odds ratios (OR) of small for gestational age babies, premature births, and perinatal deaths in singletons (gestation >/=22 weeks or birthweight >/=500 g) born to 2546 Norwegian women (>20 years) who had conceived at least one child spontaneously and another after assisted fertilisation among 1 200 922 births after spontaneous conception and 8229 after assisted fertilisation., Findings: In the whole study population, assisted-fertilisation conceptions were associated with lower mean birthweight (difference 25 g, 95% CI 14 to 35), shorter duration of gestation (2.0 days, 1.6 to 2.3) and increased risks of small for gestational age (OR 1.26, 1.10 to 1.44), and perinatal death (1.31, 1.05 to 1.65) than were spontaneous conceptions. In the sibling-relationship comparisons, the spontaneous versus the assisted-fertilisation conceptions showed a difference of only 9 g (-18 to 36) in birthweight and 0.6 days (-0.5 to 1.7) in gestational age. For assisted fertilisation versus spontaneous conception in the sibling-relationship comparisons, the OR for small for gestational age was 0.99 (0.62 to 1.57) and that for perinatal mortality was 0.36 (0.20 to 0.67)., Interpretation: Birthweight, gestational age, and risks of small for gestational age babies, and preterm delivery did not differ among infants of women who had conceived both spontaneously and after assisted fertilisation. The adverse outcomes of assisted fertilisation that we noted compared with those in the general population could therefore be attributable to the factors leading to infertility, rather than to factors related to the reproductive technology.

Objective: This study was undertaken to assess changes in placenta growth factor and soluble fms-like tyrosine kinase-1 as predictors of preeclampsia., Study Design: Nested case-control study of 154 preeclampsia cases delivered preterm and 190 delivered at term, and 392 controls., Results: Comparing the lowest and highest quartile of placenta growth factor increase from first to second trimester, the odds for preterm preeclampsia was 13.8 (95% CI, 4.4-43.2) higher for women with the lowest increase. Compared with controls, women with preterm preeclampsia had lower soluble fms-like tyrosine kinase-1 in the first, but higher in second trimester. Comparing highest and lowest quartile of increase, the odds for preterm preeclampsia was 9.2 (95% CI 3.4-25.0) higher for women with highest increase. Low placenta growth factor and high soluble fms-like tyrosine kinase-1 increase combined yielded extremely high relative risk of preterm preeclampsia (odds ratio, 35.3, 95% CI, 7.6-164.2), compared with the combination of high (placenta growth factor) and low (soluble fms-like tyrosine kinase-1) increase., Conclusion: Low placenta growth factor and high soluble fms-like tyrosine kinase-1 increase from first to second trimester are strong predictors of preeclampsia.

Objective: To study the prevalence and possible risk factors for chronic critical lower limb ischaemia (CLI) in an unselected population of 20,291 Norwegian men and women 40-69 years of age., Methods: Between 1995 and 1997, all residents 20 years or older in Nord-Trøndelag County, Norway, were invited to participate in a population study (the HUNT 2 Study). Among the 71.2% who attended, 20,291 participants 40-69 years of age responded to questions specifically aimed at identifying CLI. Chronic critical ischaemia was suspected if participants indicated: (1) ulcers on toes, foot or ankle that had failed to heal and/or; (2) persistent pain in the forefoot while in the supine position, but with relief of this pain when standing up. Using logistic regression analyses, we estimated the association between the prevalence of CLI and smoking, diabetes mellitus, previous cardiovascular events, blood lipids and glucose levels, and body mass index (BMI)., Results: The age-adjusted prevalence of CLI was 0.26% among men and 0.24% among women, and there was no gender difference in any age group (age-adjusted OR = 0.91, 95% CI = 0.52-1.58). The presence of increased age, diabetes mellitus, angina pectoris, high triglyceride levels, and high BMI were all independently associated with higher prevalence of CLI., Conclusion: The prevalence of CLI was 0.24%, similar for both genders, and increased with age. Risk factors usually seen in atherosclerotic patients were associated with suspected CLI.

Purpose: To study serum lipids, body mass index (BMI), and body shape in relation to intermittent claudication (IC) in 19,748 men and women 40-69 years of age., Method: All residents (1995-1997) in Nord-Trøndelag County, Norway, were invited to attend the cross sectional study and received a Norwegian translation of the WHO/Rose questionnaire on intermittent claudication and the Edinburgh claudication questionnaire. Blood lipids and anthropometric data were measured at a consecutive examination. Odds ratios (OR) were estimated for associations with IC by multiple regression analysis., Results: The ratio of total cholesterol to HDL cholesterol (TC/HDL cholesterol) (P trend(men)=.023; P trend(women)<.001) and triglycerides (P trend(men)=.029; P trend(women)=.002) were positively associated with the prevalence of IC. HDL cholesterol was negatively (P trend(men)=.131; P trend(women)<.001) associated, whereas BMI (P trend(women)=.032), waist circumference (P trend(women)=.021), and hip circumference (P trend(women)=.020) were positively associated with IC in women, but not in men. Adjustment for smoking, diabetes, and systolic or diastolic blood pressure did not change the results., Conclusion: TC/HDL cholesterol and triglycerides were positively, and HDL cholesterol negatively associated with IC in both genders. In women, but not in men, BMI, waist and hip circumference were positively associated with IC.

Background: It takes a higher number of male than female embryos to produce a live born infant. The unbalanced pregnancy survival by offspring sex may also be reflected in higher proportion of preterm male births, and in unbalanced sex distribution in certain pregnancy conditions, such as preeclampsia., Methods: We used data from the Medical Birth Registry of Norway, a population-based registry that has recorded births since 1967. For this study, we used information on offspring sex and length of gestation that was available for 1691053 (92.8%) singleton births among a total of 1822982 births from 1967 to 1998. We estimated sex ratios and perinatal mortality by length of gestation, and assessed whether the ratio of offspring sex in preeclampsia varied by length of gestation., Results: For preterm births, there was a strong male dominance. Within five categories of gestational age between 16 and 36 weeks, the male/female ratios were 2.48, 1.26, 1.28, 1.32, and 1.28. At weeks 37-39, the sex ratio was 1.17, but at weeks 40-42 the number of male and female births was practically identical (sex ratio 1.00). Over all, the male/female ratio was 1.06. Perinatal mortality was consistently higher in males across the whole range of gestational age; in total it was 21% (95% CI, 18-25%) higher in male offspring. In preeclampsia with preterm delivery (<37 weeks), the sex ratio was reversed: female offspring was substantially more common than males (sex ratio 0.87), but in preeclampsia with delivery at term (37-42 weeks), the proportion of males was higher (sex ratio 1.06) than for females., Conclusion: The sex differences by length of gestation and in preeclampsia may reflect that male embryos are subject to stronger intrauterine selection forces than females. Possibly, implantation may be the critical event, where offspring sex may be one of the factors that determine success.

Objectives: to investigate the prevalence of intermittent claudication (IC) in an unselected population of nearly 20000 individuals between 40 and 69 years of age., Design: epidemiologic investigation of residents in Nord-Trøndelag County, Norway., Material and Methods: between 1995 and 1997, all residents 20 years of age or older in Nord-Trøndelag County, Norway, were invited to attend the HUNT Study. A total of 19748 participants between 40 and 69 years of age responded to questions related to the symptoms of intermittent claudication. We estimated the prevalence of IC based on these questions., Results: the age-adjusted prevalence of intermittent claudication in the total population was 1.1% for men and 1.2% for women. We found an increase in the prevalence of IC by age, however, no sex differences were observed., Conclusion: the prevalence of intermittent claudication increased gradually by age. However, in contrast to previous reports, there was no difference by sex.

Objective: The objective of this study was to compare umbilical cord plasma leptin between infants of mothers who experienced preeclampsia and infants of control subjects and to study the relation between cord plasma leptin and infant obesity, as indicated by ponderal index., Study Design: On the basis of a population of approximately 13,000 deliveries, we compared cord plasma leptin from preeclamptic (n = 256 women) and control pregnancies (n = 607 women) after taking the differences in gestational age and ponderal index into account., Results: Cord plasma leptin increased strongly with gestational age, both in the preeclampsia group and the control subjects (P <.01), but at each gestational age the preeclampsia group had higher leptin levels than control subjects (P <.01). Adjustment for the higher ponderal index among control subjects (P <.05) did not alter the difference in leptin levels between the groups., Conclusion: We found higher levels of umbilical cord plasma leptin in infants of mothers who had preeclampsia (compared with infants of control subjects) after adjusting for differences in gestational age, gender, and infant ponderal index.