Melton, L. Joseph

Abstract An age-stratified sample of 304 women from Rochester, Minnesota, aged 30–94 years (median 60 years) at baseline underwent measurement of femoral neck bone mineral density (BMD) over a follow-up period extending to 16 years. The average rate of change in femoral neck BMD was −1.0% per year (range −10.0% to +13.4%) and did not vary significantly with age. Because there was no marked increase in the rate of loss around the time of menopause, nor convincing evidence of there being a subset of fast losers, there was fairly good tracking of individual values over time; the correlation of baseline with femoral neck BMD values 16 years later was 0.83. Although a large number of potential determinants was assessed, the only consistent predictor of femoral neck bone loss in women of different ages was baseline femoral neck BMD (r = −0.15; p = 0.023). Otherwise, different sets of risk factors were identified for premenopausal women, women within 20 years of menopause, and women 20 years or more postmenopausal, but the predictive power of these different multivariate models was modest. Nonetheless, these data indicate that femoral neck BMD is quite predictable for extended periods of time. This is reassuring with respect to the use of statistical models that incorporate such data to estimate future fracture risk.

Abstract While severe primary hyperparathyroidism (HPT) is clearly associated with osteitis fibrosa cystica, it remains uncertain whether mild, asymptomatic primary HPT adversely affects the skeleton. Thus, we assessed the incidence of age-related fractures in a large, population-based inception cohort of 407 cases of primary HPT (93 men and 314 women) recognized during the 28-year period, 1965–1992. Fracture risk was assessed by comparing new fractures at each site to the number expected from gender- and age-specific fracture incidence rates for the general population (standardized incidence ratios, SIRs). These community patients with primary HPT mostly had mild disease (mean ± SD serum calcium, 10.9 ± 0.6 mg/dl). Altogether, 471 fractures occurred during 5766 person-years of follow-up. Overall fracture risk was significantly increased in these patients (SIR 1.3, 95% confidence interval [CI] 1.1–1.5). Primary HPT was associated with an increased risk of vertebral (SIR 3.2, 95% CI 2.5–4.0), distal forearm (SIR 2.2, 95% CI 1.6–2.9), rib (SIR 2.7, 95% CI 2.1–3.5), and pelvic fractures (SIR 2.1, 95% CI 1.1–3.5). The risk of proximal femur fractures was only marginally increased (SIR 1.4, 95% CI 1.0–2.0). By univariate analysis, increasing age and female gender were significant predictors of fracture risk, although higher serum calcium levels were also associated with increased fracture risk, and parathyroid surgery may have had a protective effect. By multivariate analysis, however, only age (relative hazard [RH] per 10-year increase, 1.6, 95% CI 1.4–1.9) and female gender (RH 2.3, 95% CI 1.2–4.1) remained significant independent predictors of fracture risk. Thus, primary HPT among unselected patients in the community is associated with a significant increase in the risk of vertebral, Colles', rib, and pelvic fractures. These data have important implications for the current trend to recommend nonsurgical management for patients with mild primary HPT.

Objective— This study was undertaken to examine the association between bicuspid aortic valve (BAV) and aortic dilatation in the community. The association between BAV and aortic dilatation has been reported predominantly in retrospective studies in patients mostly with valvular dysfunction or selected surgical patients from tertiary referral centers. An independent association of BAV and aortic dilatation in a community-based study has not been demonstrated. Methods and Results— In a geographically defined population of Olmsted County, Minnesota, residents with BAV (n=44, age 35±13 years) without hemodynamically significant obstruction or regurgitation and matched controls with normal tricuspid aortic valves were identified by transthoracic echocardiography. The two groups were compared with respect to measurements of the aorta. The BAV and control groups differed with respect to size of the aortic anulus (23.2±2.4 versus 21.6±2.4 mm; P =0.002), aortic sinus (33.5±4.6 versus 30.3±4.1 mm; P =0.0001), and proximal ascending aorta (33.3±6.5 versus 27.9±3.6 mm; P =0.0001). There was no difference in the size of the aortic arch (24.2±3.6 versus 25.3±3.4 mm; P =0.16). These differences were maintained when the groups were stratified by sex and blood pressure. The relationship between bicuspid aortic valve and aortic dilatation was maintained when adjusting for factors related to fluid mechanics and hemodynamics such as systolic blood pressure, diastolic blood pressure, left ventricular ejection time, and peak aortic valve velocity. Conclusions— In a community-based study, BAV is associated with an alteration of aortic dimensions even in the absence of hemodynamically significant aortic valve stenosis or regurgitation.

Background— The outcome of mitral valve prolapse (MVP) is controversial, with marked discrepancies in reported complication rates. Methods and Results— We conducted a community study of all Olmsted County, Minn, residents first diagnosed with asymptomatic MVP between 1989 and 1998 (N=833). Diagnosis, motivated by auscultatory findings (n=557) or incidental (n=276), was always confirmed by echocardiography with the use of current criteria. End points analyzed during 4581 person-years of follow-up were mortality (n=96, 19±2% at 10 years), cardiovascular morbidity (n=171), and MVP-related events (n=109, 20±2% at 10 years). The most frequent primary risk factors for cardiovascular mortality were mitral regurgitation from moderate to severe ( P =0.002, n=131) and, less frequently, ejection fraction <50% ( P =0.003, n=31). Secondary risk factors independently predictive of cardiovascular morbidity were slight mitral regurgitation, left atrium ≥40 mm, flail leaflet, atrial fibrillation, and age ≥50 years (all P <0.01). Patients with only 0 or 1 secondary risk factor (n=430) had excellent outcome, with 10-year mortality of 5±2% ( P =0.17 versus expected), cardiovascular morbidity of 0.5%/y, and MVP-related events of 0.2%/y. Patients with ≥2 secondary risk factors (n=250) had mortality similar to expected ( P =0.20) but high cardiovascular morbidity (6.2%/y, P <0.01) and notable MVP-related events (1.7%/y, P <0.01). Patients with primary risk factors (n=153) showed excess 10-year mortality (45±9%, P =0.01 versus expected), high morbidity (18.5%/y, P <0.01), and high MVP-related events (15%/y, P <0.01). Conclusions— Natural history of asymptomatic MVP in the community is widely heterogeneous and may be severe. Clinical and echocardiographic characteristics allow separation of the majority of patients with excellent prognosis from subsets of patients displaying, during follow-up, high morbidity or even excess mortality as direct a consequence of MVP.