The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly.

Objective : To establish whether fetal growth rate (as distinct from size at birth) is associated with mortality from ischaemic heart disease. Design : Cohort study based on uniquely detailed obstetric records with 97% follow up over the entire life course and linkage to census data in adult life. Subjects : All 14 611 babies delivered at the Uppsala Academic Hospital, Sweden, during 1915-29 followed up to end of 1995. Main outcome measures : Mortality from ischaemic heart disease and other causes. Results : Cardiovascular disease showed an inverse association with birth weight for both men and women, although this was significant only for men. In men a 1000 g increase in birth weight was associated with a proportional reduction in the rate of ischaemic heart disease of 0.77 (95% confidence interval 0.67 to 0.90). Adjustment for socioeconomic circumstances at birth and in adult life led to slight attenuation of this effect. Relative to the lowest fourth of birth weight for gestational age, mortality from ischaemic heart disease in men in the second, third, and fourth fourths was 0.81 (0.66 to 0.98), 0.63 (0.50 to 0.78), and 0.67 (0.54 to 0.82), respectively. The inclusion of birth weight per se and birth weight for gestational age in the same model strengthened the association with birth weight for gestational age but removed the association with birth weight. Conclusions : This study provides by far the most persuasive evidence of a real association between size at birth and mortality from ischaemic heart disease in men, which cannot be explained by methodological artefact or socioeconomic confounding. It strongly suggests that it is variation in fetal growth rate rather than size at birth that is aetiologically important.

Objective : To establish whether the relation between size at birth and non-insulin dependent diabetes is mediated through impaired β cell function or insulin resistance. Design : Cohort study. Setting : Uppsala, Sweden. Subjects : 1333 men whose birth records were traced from a cohort of 2322 men born during 1920-4 and resident in Uppsala in 1970. Main outcome measures : Intravenous glucose tolerance test at age 50 years and non-insulin dependent diabetes at age 60 years. Results : There was a weak inverse correlation (r=-0.07, P=0.03) between ponderal index at birth and 60 minute insulin concentrations in the intravenous glucose tolerance test at age 50 years. This association was stronger (r=-0.19, P=0.001) in the highest third of the distribution of body mass index than in the other two thirds (P=0.01 for the interaction between ponderal index and body mass index). Prevalence of diabetes at age 60 years was 8% in men whose birth weight was less than 3250 g compared with 5% in men with birth weight 3250 g or more (P=0.08; 95% confidence interval for difference −0.3% to 6.8%). There was a stronger association between diabetes and ponderal index: prevalence of diabetes was 12% in the lowest fifth of ponderal index compared with 4% in the other four fifths (P=0.001; 3.0% to 12.6%). Conclusion : These results confirm that reduced fetal growth is associated with increased risk of diabetes and suggest a specific association with thinness at birth. This relation seems to be mediated through insulin resistance rather than through impaired β cell function and to depend on an interaction with obesity in adult life.

Background— Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. Methods and Results— The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P <0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (50 mL · min ⁻¹ · 1.73 m ⁻² and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. Conclusions— Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.

Objectives : To clarify the type of fetal growth impairment associated with increased blood pressure in adult life, and to establish whether this association is influenced by obesity and is mediated through impairment of insulin action. Design : Cross sectional survey with retrospective ascertainment of size at birth from obstetric archives. Subjects : 1333 men resident in Uppsala, Sweden, who took part in a 1970 study of coronary risk factors at age 50 and for whom birth weight was traced. Main outcome measures : Systolic and diastolic blood pressure at age 50. Results : In the full study population for a 1000 g increase in birth weight there was a small change in systolic blood pressure of −2.2 mm Hg (95% confidence interval −4.2 to −0.3 mm Hg) and in diastolic blood pressure of −1.0 mm Hg (−2.2 to 0.1 mm Hg). Much stronger effects were observed among men who were born at term and were in the top third of body mass index at age 50, for whom a 1000 g increase in birth weight was associated with a change of −9.1 mm Hg (−16.4 to −1.9 mm Hg) systolic and −4.2 mm Hg (−8.3 to −0.1 mm Hg) diastolic blood pressure. Men who were light at birth (<3250 g) but were of above median adult height had particularly high blood pressure. Adjustment for insulin concentrations reduced the associations of birth weight with systolic and diastolic blood pressure. Conclusions : A failure to realise growth potential in utero (as indicated by being light at birth but tall as an adult) is associated with raised adult blood pressure. Impaired fetal growth may lead to substantial increases in adult blood pressure among only those who become obese. Metabolic disturbances, possibly related to insulin resistance, may provide a pathway through which fetal growth affects blood pressure.