Elderly cohort study subjects unable to return for follow-up have lower bone mass than those who can return

Longitudinal studies of osteoporosis in older persons may underestimate bone loss because of a lack of follow-up measurements on subjects too frail to return. The authors addressed this possible bias as part of the population-based Framingham Study; in 1996-1997, they used quantitative ultrasound to assess the bone status of elderly subjects regardless of their ability to return to the clinic. Broadband ultrasound attenuation (BUA) and speed of sound of the calcaneus (heel) were measured in 433 subjects at the Framingham, Massachusetts, clinic and in 167 subjects at their homes or nursing homes. All ultrasound parameters were measured with intramachine coefficients of variation of <6.0%. The mean BUA for those subjects evaluated at the clinic was higher than for those measured at home (9.2% higher for men, p = 0.081; 8.6% higher for women, p = 0.034). After adjustment for age and weight, the differences in BUA were no longer significant. Among the elderly subjects participating in this longitudinal cohort study, those who were unable to return for follow-up were older, weighed less, and had a lower BUA than those who did return, suggesting that longitudinal studies of changes in bone mass with aging may underestimate the true population values.     

Variation in estrogen-related genes associated with cardiovascular phenotypes and circulating estradiol, testosterone, and dehydroepiandrosterone sulfate levels

BACKGROUND: Younger age at the onset of menopause and lower circulating levels of estrogen are risk factors for cardiovascular disease. Several studies have detected associations between variations in genes encoding estrogen receptors alpha (ESR1) and beta (ESR2), and enzyme aromatase (CYP19A1), which regulates the estrogen to testosterone ratio, and cardiovascular phenotypes in the Framingham Heart Study. To explore potential mechanisms by which these gene variants may contribute to cardiovascular disease, we tested the hypothesis that the polymorphisms were associated with endogenous steroid hormone levels. METHODS: Multiple regression analysis was used to assess the relation between reported polymorphisms and total serum estradiol, testosterone, and dehydroepiandrosterone sulfate levels in 834 men and 687 women who attended the third and fourth Framingham Heart Study examination cycles. RESULTS: In men, significant associations were detected between CYP19A1 polymorphisms and estradiol and testosterone levels, and the estradiol to testosterone ratio (P ranges 0.0005-0.01). Specifically, carriers of common haplotype rs700518[G]-(TTTA)(n) [L]-rs726547[C] had higher estradiol levels (5% per copy; P = 0.0004), lower testosterone levels (17% per copy; P = 0.036), and a higher estradiol to testosterone ratio (24% per copy; P < 0.0001) compared with the rs700518[A]-(TTTA)(n) [S]-rs726547[C] carriers. In addition, postmenopausal carriers of the ESR2 (CA)(n) long allele and rs1256031 [C] allele had moderately higher estradiol levels (P < or = 0.03). No significant associations with the ESR1 variants were detected. CONCLUSIONS: Our findings suggest that variations in CYP19A1 correlate with steroid hormone levels in men. Knowledge that a specific carrier status may predispose to altered steroid hormone levels may lead to targeted intervention strategies to reduce health risks in genetically susceptible individuals.     

The incidence and natural history of Raynaud's phenomenon in the community

OBJECTIVE: Raynaud's phenomenon (RP) is a common disorder, yet its incidence and natural history are unknown. Our objective was to determine the incidence and natural history of RP not associated with a connective tissue disease in a large, community-based population. METHODS: Using serial examinations of the Framingham Heart Study offspring cohort, we collected data regarding RP symptoms for 717 women and 641 men over a 7-year period. We used validated criteria for RP classification and categorized participants as having incident, persistent, or remitted RP. We performed sex-specific analyses of RP status by age, body mass index, vibratory tool use, season of examination, state of residence, use of antihypertensive medications, and smoking status. RESULTS: The mean +/- SD age of participants was 53.5 +/- 10 years. The incidence of RP was 2.2% in women (n = 14) and 1.5% in men (n = 9). Of the 78 women and 50 men who had RP at baseline, 36% of women (n = 28) and 36% of men (n = 18) had persistent RP. RP remitted in 64% of women (n = 50) and 64% of men (n = 32), with 41 women and 25 men meeting no or only 1 RP criterion at followup. RP episodes were infrequent and rarely interfered with daily activities. CONCLUSION: This is the first prospective study to determine the incidence and natural history of RP in a community-based cohort. Our data demonstrate that RP not associated with a connective tissue disease is frequently a transient phenomenon and rarely interferes with daily activities.     

Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring

Context  Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events. Objective  To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events. Design  Inception cohort study. Setting  Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971. Participants  All Framingham Offspring Study participants (aged =" BORDER="0">30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort. Main Outcome Measures  We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression. Results  Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk. Conclusions  Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adults. Addition of parental information may help clinicians and patients with primary prevention of cardiovascular disease, when treatment decisions may be difficult in patients at intermediate risk based on levels of single or multiple risk factors. These data also support further research into genetic determinants of cardiovascular risk.      

Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study

Background Peripheral arterial disease (PAD) is associated with an increased risk for mortality. We sought to assess the prevalence of PAD and its risk factors in a population-based sample. Methods We examined 1554 males and 1759 females with a mean age of 59 years who attended a Framingham Offspring Study examination from 1995 to 1998. PAD was defined by an ankle-brachial blood pressure index of <0.9. Age- and sex-adjusted and multivariable logistic regression analyses were performed to identify factors associated with PAD. Results The prevalences of PAD, current intermittent claudication, lower extremity bruits and surgical intervention were 3.9%, 1.9%, 2.4% and 1.4% in males and 3.3%, 0.8%, 2.3% and 0.5% in females. Hypercholesterolemia, high-density lipoprotein cholesterol, triglyceride, diabetes, hypertension, current smoking, pack-years of smoking, body mass index, fibrinogen, and prevalent coronary disease were associated with PAD in age- and sex-adjusted analyses. Odds ratios and 95% CIs for significant associations identified from multivariable analyses are as follows: each 10 years of age, 2.6 (2.0, 3.4); hypertension, 2.2 (1.4, 3.5); smoking, 2.0 (1.1, 3.4); 10 pack-years of smoking, 1.3 (1.2, 1.4); 50 mg/dL of fibrinogen, 1.2 (1.1, 1.4); 5 mg/dL of high-density lipoprotein, 0.9 (0.8, 1.0); coronary disease, 2.6 (1.6, 4.1). Conclusions Smoking cessation and hypertension control are important goals in the aim to reduce PAD and its associated impact on quality of life, functional decline, and risk for subsequent cardiovascular disease. (Am Heart J 2002;143:961-5.)