Early growth and death from cardiovascular disease in women.

OBJECTIVE--To determine whether the link suggested between growth in utero and during infancy and death from cardiovascular disease in men is also present in women. DESIGN--Follow up study of women and men whose birth weight and weight at 1 year of age had been recorded. SETTING--Hertfordshire, England. SUBJECTS--5585 women and 10,141 men born during 1911-30. MAIN OUTCOME MEASURES--Standardised mortality ratios for cardiovascular disease. RESULTS--Among women and men death rates from cardiovascular disease fell progressively between the low and high birth weights groups (chi 2 = 4.3, p = 0.04 for women, chi 2 = 8.5, p < 0.005 for men). Cardiovascular deaths in men but not women were also strongly related to weight at 1 year, falling progressively between the low and high weight groups (chi 2 = 27.5, p < 0.0001). The highest cardiovascular death rates in women were among those with below average birth weight but above average weight at 1 year. In men the highest rates were among those with below average birth weight and below average weight at 1 year. CONCLUSION--Relations between cardiovascular disease and birth weight are similar in men and women. In men cardiovascular disease is also related to weight gain in infancy.     

Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life.

OBJECTIVE--To determine whether reduced fetal and infant growth are associated with higher plasma fibrinogen and factor VII concentrations in adult life. DESIGN--Follow up study of men born during 1920-30 whose weights at birth and at 1 year had been recorded by health visitors, and men born during 1935-43 whose size at birth had been measured in detail. SETTING--Hertfordshire and Preston, England. SUBJECTS--591 men born in east Hertfordshire who still lived there and 148 men born in Preston who still lived in or close to the city. MAIN OUTCOME MEASURES--Plasma fibrinogen and factor VII concentrations. RESULTS--Among men in Hertfordshire mean plasma fibrinogen and factor VII concentrations fell with increasing weight at 1 year (from 3.21 g/l in men of less than or equal to 18 lb to 2.93 g/l in men greater than or equal to 27 lb and from 122% of standard to 103%; p less than 0.001, p less than 0.005 respectively). The trends were independent of cigarette smoking, alcohol consumption, body mass index, and social class. Neither plasma fibrinogen nor factor VII concentration was related to birth weight. In men in Preston, however, fibrinogen concentration fell progressively as the ratio of placental weight to birth weight decreased (p = 0.01). CONCLUSIONS--Reduced growth in fetal life and infancy is strongly related to high plasma concentrations of the haemostatic factors fibrinogen and factor VII. This may be a persisting response to impaired liver development during a critical early period.     

Weight in infancy and prevalence of coronary heart disease in adult life.

OBJECTIVE--To determine whether low birth weight and low weight at 1 year are followed by an increased prevalence of coronary heart disease in adult life. DESIGN--A follow up study of men born during 1920-30 whose birth weights and weights at 1 year were recorded. SETTING--Hertfordshire, England. SUBJECTS--290 men born and still living in East Hertfordshire. MAIN OUTCOME MEASURE--The prevalence of coronary heart disease, defined by the Rose/WHO chest pain questionnaire, standard electrocardiographic criteria, or history of coronary artery angioplasty or graft surgery. RESULTS--42 (14%) men had coronary heart disease. Their mean birth weight, 7.9 lb (3600 g), was the same as that of the other men. Their mean weight at 1 year, 21.8 lb (9.9 kg), was 1 lb (454 g) lower (95% confidence interval 0.1 to 1.8, P = 0.02). Percentages of men with coronary heart disease fell from 27% in those who weighed 18 lb (8.2 kg) or less at 1 year to 9% in those who weighed more than 26 lb (11.8 kg) (P value for trend = 0.03). This trend occurred in both smokers and non-smokers and within each social class. CONCLUSION--These findings add to the evidence that coronary heart disease is "programmed" during early growth.     

Fetal and infant growth and impaired glucose tolerance at age 64.

OBJECTIVE--To discover whether reduced fetal and infant growth is associated with non-insulin dependent diabetes and impaired glucose tolerance in adult life. DESIGN--Follow up study of men born during 1920-30 whose birth weights and weights at 1 year were known. SETTING--Hertfordshire, England. SUBJECTS--468 men born in east Hertfordshire and still living there. MAIN OUTCOME MEASURES--Fasting plasma glucose, insulin, proinsulin, and 32-33 split pro-insulin concentrations and plasma glucose and insulin concentrations 30 and 120 minutes after a 75 g glucose drink. RESULTS--93 men had impaired glucose tolerance or hitherto undiagnosed diabetes. They had had a lower mean birth weight and a lower weight at 1 year. The proportion of men with impaired glucose tolerance fell progressively from 26% (6/23) among those who had weighted 18 lb (8.16 kg) or less at 1 year to 13% (3/24) among those who had weighed 27 lb (12.25 kg) or more. Corresponding figures for diabetes were 17% (4/23) and nil (0/24). Plasma glucose concentrations at 30 and 120 minutes fell with increasing birth weight and weight at 1 year. Plasma 32-33 split proinsulin concentration fell with increasing weight at 1 year. All these trends were significant and independent of current body mass. Blood pressure was inversely related to birth weight and strongly related to plasma glucose and 32-33 split proinsulin concentrations. CONCLUSIONS--Reduced growth in early life is strongly linked with impaired glucose tolerance and non-insulin dependent diabetes. Reduced early growth is also related to a raised plasma concentration of 32-33 split proinsulin, which is interpreted as a sign of beta cell dysfunction. Reduced intrauterine growth is linked with high blood pressure, which may explain the association between hypertension and impaired glucose tolerance.     

Maternal inflammation, growth retardation, and preterm birth: insights into adult cardiovascular disease

The "fetal origin of adult disease Hypothesis" originally described by Barker et al. identified the relationship between impaired in utero growth and adult cardiovascular disease risk and death. Since then, numerous clinical and experimental studies have confirmed that early developmental influences can lead to cardiovascular, pulmonary, metabolic, and psychological diseases during adulthood with and without alterations in birth weight. This so called "fetal programming" includes developmental disruption, immediate adaptation, or predictive adaptation and can lead to epigenetic changes affecting a specific organ or overall health. The intrauterine environment is dramatically impacted by the overall maternal health. Both premature birth or low birth weight can result from a variety of maternal conditions including undernutrition or dysnutrition, metabolic diseases, chronic maternal stresses induced by infections and inflammation, as well as hypercholesterolemia and smoking. Numerous animal studies have supported the importance of both maternal health and maternal environment on the long term outcomes of the offspring. With increasing rates of obesity and diabetes and survival of preterm infants born at early gestational ages, the need to elucidate mechanisms responsible for programming of adult cardiovascular disease is essential for the treatment of upcoming generations.     

Fetal and infant growth and cardiovascular risk factors in women.

OBJECTIVE--To examine whether cardiovascular risk factors in women are related to fetal and infant growth. DESIGN--Follow up study of women born 1923-30 whose birth weights and weights at one year were recorded. SETTING--Hertfordshire. SUBJECTS--297 women born and still living in East Hertfordshire. MAIN OUTCOME MEASURES--Plasma glucose and insulin concentrations during a standard oral glucose tolerance test; fasting plasma proinsulin and 32-33 split proinsulin concentrations; blood pressure; fasting serum total, low density lipoprotein and high density lipoprotein cholesterol, triglyceride, and apolipoprotein A I and B concentrations; and plasma fibrinogen and factor VII concentrations. RESULTS--Fasting plasma concentrations of glucose, insulin, and 32-33 split proinsulin fell with increasing birth weight (P = 0.04, P = 0.002, and P = 0.0002 respectively, when current body mass index was allowed for). Glucose and insulin concentrations 120 minutes after an oral glucose load showed similar trends (P = 0.03 and P = 0.02). Systolic blood pressure, waist:hip ratio, and serum triglyceride concentrations also fell with increasing birth weight (P = 0.08, P = 0.07, and P = 0.07 respectively), while serum high density lipoprotein cholesterol concentrations rose (P = 0.04). At each birth weight women who currently had a higher body mass index had higher levels of risk factors. CONCLUSION--In women, as in men, reduced fetal growth leads to insulin resistance and the associated disorders: raised blood pressure and high serum triglyceride and low serum high density lipoprotein cholesterol concentrations. The highest values of these coronary risk factors occur in people who were small at birth and became obese. In contrast with men, low rates of infant growth did not predict levels of risk factors in women.     

Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease.

OBJECTIVE--To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease. DESIGN--Follow up study of men born during 1911-30 whose birth weights, weights at 1 year, and childhood illnesses were recorded at the time by health visitors. SETTING--Hertfordshire, England. SUBJECTS--5718 men born in the county during 1911-30 and a subgroup of 825 men born in the county during 1920-30 and still living there. MAIN OUTCOME MEASURES--Death from chronic obstructive airways disease, mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and respiratory symptoms. RESULTS--55 men died of chronic obstructive airways disease. Death rates fell with increasing birth weight and weight at 1 year. Mean FEV1 at age 59 to 70 years, adjusted for height and age, rose by 0.06 litre (95% confidence interval 0.02 to 0.09) with each pound (450 g) increase in birth weight, independently of smoking habit and social class. Bronchitis or pneumonia in infancy was associated with a 0.17 litre (0.02 to 0.32) reduction in adult FEV1 and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0.22 litre (0.02 to 0.42) reduction in adult FEV1. CONCLUSIONS--Lower birth weight was associated with worse adult lung function. Intrauterine influences which retard fetal weight gain may irrecoverably constrain the growth of the airways. Bronchitis, pneumonia, or whooping cough in infancy further reduced adult lung function. They also retarded infant weight gain. Consistent with this, death from chronic obstructive airways disease in adult life was associated with lower birth weight and weight at 1 year. Promoting lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of chronic obstructive airways disease in the next generation.     

Risk factors for perinatal mortality in Canada

A population-based computer record-linkage study of infant births and deaths in 1978 and 1979 in eight Canadian provinces (Quebec and Newfoundland were excluded) was undertaken to permit analysis of perinatal mortality in relation to maternal and infant characteristics. Perinatal mortality rates were significantly higher in nonurban than in urban areas (p < 0.05). A logistic regression model was used to assess the effects on perinatal mortality of variables reported on birth and stillbirth records. This model included length of gestation, infant''s birth weight and sex, number of previous births and number of previous stillbirths as well as an interaction term for length of gestation and birth weight. For early-neonatal mortality, odds ratios over 8 were observed for birth weight less than 2500 g or gestation less than 35 weeks. About 75% of early-neonatal mortality was attributable to low birth weight or fetal immaturity. Greater emphasis should be placed on the prevention of low birth weight.     

Growth in utero and serum cholesterol concentrations in adult life.

OBJECTIVE--To see whether reduced rates of fetal growth are related to raised serum cholesterol concentrations in adult life. DESIGN--Follow up study of men and women whose size at birth had been recorded. SETTING--Jessop and Northern General Hospitals, Sheffield. SUBJECTS--219 men and women born in the Jessop Hospital during 1939-40. MAIN OUTCOME MEASURES--Serum concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. RESULTS--Men and women who had had a small abdominal circumference at birth had raised serum concentrations of total and low density lipoprotein cholesterol and apolipoprotein B. This was independent of the duration of gestation. Serum concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval 0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The corresponding figure for serum low density lipoprotein cholesterol was 0.26 mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07). Small head and chest circumferences at birth and short length were each associated with raised serum low density lipoprotein cholesterol concentrations but the trends disappeared in a simultaneous regression with abdominal circumference at birth. The association between abdominal circumference at birth and low density lipoprotein cholesterol concentration was independent of social class, current body weight, cigarette smoking, and alcohol consumption. CONCLUSION--Raised serum cholesterol concentrations in adult life are associated with impaired growth during late gestation, when fetal undernutrition has a disproportionate effect on liver growth. Impaired liver growth may permanently alter low density lipoprotein cholesterol metabolism.     

Mortality from cardiovascular disease among interregional migrants in England and Wales.

OBJECTIVE--To investigate the extent to which geographical variations in mortality from ischaemic heart disease and stroke in Britain are influenced by factors in early life or in adulthood. DESIGN--Longitudinal study of migrants. SUBJECTS--1% sample of residents in England and Wales born before October 1939 and enumerated at the 1971 census (the Office of Population Censuses and Surveys'' longitudinal study). MAIN OUTCOME MEASURE--18,221 deaths from ischaemic heart disease and 9899 deaths from stroke during 1971-88 were analysed by areas of residence in 1939 and 1971. These included 2928 deaths from ischaemic heart disease and 1608 deaths from stroke among individuals moving between 14 areas defined by the major conurbations and nine standard administrative regions of England and Wales. RESULTS--The southeast to northwest gradient in mortality from ischaemic heart disease was related significantly to both the 1939 area (chi 2 = 6.09, df = 1) and area in 1971 (chi 2 = 5.05, df = 1). Geographical variations in mortality from stroke were related significantly to the 1939 area (chi 2 = 4.09, df = 1) but the effect of area in 1971 was greater (chi 2 = 8.07, df = 1). The effect of 1971 area on mortality from stroke was largely due to a lower risk of death from stroke among individuals moving into Greater London compared with migrants to the rest of the South East region (chi 2 = 4.54, df = 1). CONCLUSIONS--Geographical variations in mortality from cardiovascular disease in Britain may be partly determined by genetic factors, environmental exposures, or lifestyle acquired early in life, but the risk of fatal ischaemic heart disease and stroke changes on migration between areas with differing mortality. The low risk of death from stroke associated with residence in Greater London is acquired by individuals who move there.     

Maternal fatness and viability of preterm infants

To investigate the effect of maternal fatness on the mortality of infants born preterm up to the corrected age of 18 months 795 mother-infant pairs were studied. Maternal fatness was defined by Quetelet''s index (weight/(height²)) and all infants weighed less than 1850 g at birth. In 771 mother-infant pairs maternal age, complications of pregnancy, mode of delivery, parity, social class, and the baby''s sex and gestation were analysed by a logistic regression model for associations with infant mortality (but deaths from severe congenital abnormalities and those occurring during the first 48 hours after birth were excluded). In a subgroup of 284 mother-infant pairs all infant deaths except those from severe congenital abnormalities were analysed in association with the infant''s birth weight and gestation and the mother''s height and weight; this second analysis included another 24 infants who had died within 48 hours after birth. In the first analysis mortality overall was 7% (55/771), rising from 4% (71/173) in thin mothers (Quetelet''s index <20) to 15% (6/40) in mothers with grades II and III obesity (Quetelet''s index >30). After adjusting for major demographic and antenatal factors, including serious complications of pregnancy, maternal fatness was second in importance only to length of gestation in predicting death of infants born preterm. In the second analysis mortality overall was 15% (44/284), rising from 9% (5/53) in thin mothers to 47% (8/17) in mothers with grades II and III obesity. In both analyses the relative risk of death by 18 months post-term was nearly four times greater in infants born to obese mothers than in those born to thin mothers. In addition, maternal fatness was associated with reduced birth weight, whereas it is associated with macrosomia in term infants.These data differ fundamentally from those reported in full term babies of obese mothers. It is speculated that the altered metabolic milieu in obesity may reduce the ability of the fetus to adapt to extrauterine life if it is born preterm.     

Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study

BackgroundClose to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings.MethodsStudy population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses.ResultsCompared with a sibling born in week 37–41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population.ConclusionPreterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings.     

Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.     

Contribution of twin pregnancy to perinatal mortality and fetal growth retardation; reversal of growth retardation after birth.

A survey of factors associated with perinatal mortality in 511 twins and fetal growth retardation and its reversal in 262 twins is presented. The incidence of stillbirth was almost 50% higher in twins than in singletons and the neonatal mortality was six times as high. Eighty percent of the neonatal deaths occurred in infants born prior to or at 30 weeks of gestation; 93% of the deaths were in infants weighing less than 1500 g and 75% occurred within 48 hours of birth. Fetal malnutrition was the main cause of stillbirth, and respiratory distress syndrome and asphyxia neonatorum were the main causes of neonatal death. One quarter of the twins had fetal growth retardation, a prevalence 10 times that in singletons. In almost all, the growth retardation was reversed by high-energy feedings. Although twins represented only 1% of all pregnancies and 2% of live births, they composed 12% of infants with early neonatal death and 17% of growth-retarded infants. A program is suggested for reduction of twin mortality and morbidity.     

Maternal nutrition in early and late pregnancy in relation to placental and fetal growth.

OBJECTIVE: To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth. DESIGN: Prospective observational study. SETTING: Princess Anne Maternity Hospital, Southampton. SUBJECTS: 538 mothers who delivered at term. MAIN OUTCOME MEASURES: Placental and birth weights adjusted for the infant''s sex and duration of gestation. RESULTS: Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g(95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother''s height and body mass index and of strong relations between the mother''s birth weight and the placental and birth weights of her offspring. CONCLUSION: These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring''s risk of cardiovascular disease.     

Neutron irradiation of late mouse embryos (15-19 days) in utero

Pregnant female C57B1/6 mice were irradiated with a single whole-body dose of 0.5 Gy neutrons. The F1 hybrid embryos were exposed to the neutrons in utero on Day 17 +/- 2 of gestation. 178/439 (40.6%) of the irradiated fetuses and 26/217 (12%) of the control mice died within 2 weeks after birth. In both irradiated and control mice, most deaths (95 and 77%, respectively) occurred within 3 days of birth: most animals in both groups died on Day 2. There was no significant difference in the number of living young born per litter (7.2) between the neutron-irradiated mothers and their unirradiated controls. The irradiated mice weighed significantly less than their controls. On the first day after birth, body weights of mice irradiated in utero averaged only 85% of control weights. Body weights did not reach control levels until 6 months after birth. Several organs were weighed at regular intervals in both irradiated and control mice. Spleens and thymus glands showed no significant differences between the two groups. The livers and kidneys of the irradiated mice weighed slightly less than their controls. The brain weight of 21-day-old neutron-irradiated mice was 30-35% less than control brains. The weight loss of the brain was not only a relative loss, but also an absolute one, based on brain weight/body weight ratios. Histological analysis of the central nervous system showed pycnotic nuclei, inhibition of mitosis in neuroblasts, and cell death in the irradiated brains. The weight reduction of the brain was not due to water loss. Our hypothesis is that the early mortality after birth is related to the killing of the radiation-sensitive neuroblasts. When newborn mice (1-7 days old) were irradiated in vivo with the same neutron dose of 0.5 Gy, neither the reduction in brain weight nor the early mortality was observed. The early deaths of the neutron-irradiated mouse embryos does not appear to be caused by either the hematological or the gastrointestinal radiation syndrome.     

High serum insulin-like growth factor binding protein-1 is associated with increased cardiovascular mortality in elderly men.

Insulin-like growth factor binding protein-1 (IGFBP-1) has been implicated in the development of cardiovascular disease, but it is not known whether IGFBP-1 is related to cardiovascular mortality. We examined the relation of circulating IGFBP-1 to death from coronary heart disease, cardiovascular disease, and all causes in a cohort study consisting of 622 men aged 65 - 84 years, at baseline in 1984. Fasting serum IGFBP-1 and other risk factors were measured in 1984 and 1989. Cardiovascular events for those who died between 1984 and 1995 were analyzed, and cardiovascular diagnoses were coded centrally according to standardized procedures. Of the 622 men, 358 died between 1984 and 1995; 160 deaths were due to cardiovascular causes, 113 of which were coronary deaths. High fasting serum IGFBP-1 concentration (> 75 percentile) in 1984 was associated with increased five-year total mortality (OR 2.05, 95 % CI 1.41 - 2.99; p < 0.0002), cardiovascular mortality (OR 2.20, 95 % CI 1.37 - 3.50; p < 0.0009) and coronary heart disease mortality (OR 2.29, 95 % CI 1.35 - 3.88; p < 0.002). After adjustment for age, high serum IGFBP-1 concentrations still carried an increased risk of total mortality due to (OR 1.73, 95 % CI 1.16 - 2.59; p < 0.007), cardiovascular (OR 1.91 95 % CI 1.18 - 3.09; p < 0.008) and coronary heart disease (OR 2.02. 95 % CI 1.18 - 3.47; p < 0.01). In conclusion, high fasting serum IGFBP-1 is related to increased five-year total and cardiovascular mortality in elderly men.     

Sex differences in the fetal programming of hypertension

Background: Numerous clinical and experimental studies support the hypothesis that the intrauterine environment is an important determinant of cardiovascular disease and hypertension.Objective: This review examined the mechanisms linking an adverse fetal environment and increased risk for chronic disease in adulthood with an emphasis on gender differences and the role of sex hormones in mediating sexual dimorphism in response to a suboptimal fetal environment.Methods: This review focuses on current findings from the PubMed database regarding animal models of fetal programming of hypertension, sex differences in phenotypic outcomes, and potential mechanisms in offspring of mothers exposed to an adverse insult during gestation. For the years 1988 to 2007, the database was searched using the following terms: fetal programming, intrauterine growth restriction, low birth weight, sex differences, estradiol, testosterone, high blood pressure, and hypertension.Results: The mechanisms involved in the fetal programming of adult disease are multifactorial and include alterations in the regulatory systems affecting the long-tterm control of arterial pressure. Sex differences have been observed in animal models of fetal programming, and recent studies suggest that sex hormones may modulate activity of regulatory systems, leading to a lower incidence of hypertension and vascular dysfunction in females compared with males.Conclusions: Animal models of fetal programming provide critical support for the inverse relationship between birth weight and blood pressure. Experimental models demonstrate that sex differences are observed in the pathophysiologic response to an adverse fetal environment. A role for sex hormone involvement is strongly suggested,with modulation of the renin-angiotensin system as a possible mechanism.