No abstract

for the Thyroid Studies Collaboration C ONTROVERSY PERSISTS ON THEindications for screening and threshold levels of thyroidstimulating hormone (TSH) for treatment of subclinical hypothyroidism, 1-3 defined as elevated serum TSH levels with normal thyroxine (T 4 ) concentrations. Because subclinical hypothyroidism has been associated with hypercholesterolemia 4 and atherosclerosis, 5 screening and treatment have been advocated to prevent cardiovascular disease. 3 However, data on the associations with coronary heart disease (CHD) events and mortality are conflicting among several large prospective cohorts. [6][7][8][9] Three recent study-level metaanalyses 10-12 found modestly increased risks for CHD and mortality, but with heterogeneity among individual studies that used different TSH cutoffs, dif-See also Patient Page. CME available online at www.jamaarchivescme.com and questions on p 1392.

MD; for the Health ABC StudyBackground-Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. Methods and Results-aPWV was measured at baseline in 2488 participants from the Health, Aging and BodyComposition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated with both total mortality (relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus 1; Pϭ0.019) and cardiovascular mortality (relative risk, 2.1, 3.0, and 2.3 for quartiles 2, 3, and 4 versus 1; Pϭ0.004). aPWV quartile was also significantly associated with CHD (Pϭ0.007) and stroke (Pϭ0.001). These associations remained after adjustment for age, gender, race, systolic blood pressure, known CV disease, and other variables related to events. Conclusions-Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.

Usual gait speed of less than 1 m/s identifies persons at high risk of health-related outcomes in well-functioning older people. Provision of a clinically meaningful cutpoint for usual gait speed may facilitate its use in clinical and research settings.

Context Type 2 diabetes is associated with higher bone density (BMD) and, paradoxically, with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in diabetic patients. Objective Determine if femoral neck (FN) BMD T-score and FRAX score are associated with fracture in older diabetic adults. Design Three observational studies: Study of Osteoporotic Fractures, Osteoporotic Fractures in Men, and Health, Aging and Body Composition study. Setting Older community-dwelling adults in U.S. Participants 9,449 women; 7,436 men. Main outcome measure(s) Self-reported incident fractures, verified by radiology reports. Results Of 770 diabetic women, 84 experienced a hip and 262 a non-spine fracture during mean (SD) follow-up of 12.6 (5.3) years. Of 1,199 diabetic men, 32 experienced a hip and 133 a non-spine fracture during mean follow-up of 7.9 (2.5) years. Age-adjusted hazard ratios (HR) for one unit decrease in FN BMD T-score in diabetic women were 1.88 (95% confidence interval [CI], 1.43–2.48) for hip and 1.52 (95% CI, 1.31–1.75) for non-spine fracture. HRs in diabetic men were 5.71 (95% CI, 3.42–9.53) for hip and 2.17 (95% CI, 1.75–2.69) for non-spine fracture. FRAX score was also associated with fracture risk in diabetic participants. However, for a given T-score and age or FRAX score, diabetic participants had a higher fracture risk than those without diabetes. For a similar hip fracture risk, diabetic participants had a higher T-score than non-diabetic participants. The difference in T-score was 0.59 (95% CI, 0.31–0.87) for women and 0.38 (95% CI, 0.09–0.66) for men. Conclusions Among older adults with type 2 diabetes, FN BMD T-score and FRAX score were associated with hip and non-spine fracture risk. However, in these patients, compared with participants without diabetes, fracture risk was higher for a given T-score and age or a given FRAX score.

All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy. However, there is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive. Teriparatide should be considered as treatment for postmenopausal women and men with severe osteoporosis, as well as for patients with established glucocorticoid-induced osteoporosis who require long-term steroid treatment. Teriparatide should also be considered for the management of individuals at particularly high risk for fractures, including subjects who are younger than age 65 and who have particularly low bone mineral density measurements (T scores < or = 3.5). Teriparatide therapy is not recommended for more than 2 yr, based, in part, on the induction of osteosarcoma in a rat model of carcinogenicity. Total daily calcium intake from both supplements and dietary sources should be limited to 1500 mg together with adequate vitamin D intake (< or =1000 U/d). Monitoring of serum calcium may be safely limited to measurement after 1 month of treatment; mild hypercalcemia may be treated by withdrawing dietary calcium supplements, reducing the dosing frequency of PTH, or both. At present, concurrent therapy with antiresorptive therapy, particularly bisphosphonates, should be avoided, although sequential therapy with such agents may consolidate the beneficial effects upon the skeleton after PTH is discontinued.

Background Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting. We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts. Methods Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. Results Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age-and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio [HR], 1.24, 95% CI, 1.06–1.46), CHD mortality (HR, 1.29; 95% CI, 1.02–1.62), CHD events (HR, 1.21; 95% CI, 0.99–1.46), and AF (HR, 1.68; 95% CI, 1.16–2.43). Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% for AF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L (for both, P value for trend, ≤.03). Conclusion Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.

We examined the effect of alendronate treatment for 3-4 yr on risk of new fracture among 3658 women with osteoporosis enrolled in the Fracture Intervention Trial. This cohort included women with existing vertebral fracture and those with osteoporosis as defined by T score of less than -2.5 at the femoral neck but without vertebral fracture. All analyses were prespecified in the data analysis plan. The magnitudes of reduction of fracture incidence with alendronate were similar in both groups. The two groups were, therefore, pooled to obtain a more precise estimate of the effect of alendronate on relative risk of fracture (relative risk, 95% confidence interval): hip (0.47, 0.26-0.79), radiographic vertebral (0.52, 0.42-0.66), clinical vertebral (0.55, 0.36-0.82), and all clinical fractures (0.70, 0.59-0.82). Reductions in risk of clinical fracture were statistically significant by 12 months into the trial. We conclude that reductions in fracture risk during treatment with alendronate are consistent in women with existing vertebral fractures and those without such fractures but with bone mineral density in the osteoporotic range. Furthermore, reduction in risk is evident early in the course of treatment. This pooled analysis provides a more precise estimate of the antifracture efficacy of alendronate in women with osteoporosis than that in prior reports.