Effect of noncancerous pelvic problems on health-related quality of life and sexual functioning.

OBJECTIVE: To assess the effect of abnormal uterine bleeding and pelvic pain and pressure on health-related quality of life and sexual functioning and assess treatment satisfaction. METHODS: This is a cross-sectional study of 1,493 sociodemographically diverse women who were seeking care for noncancerous pelvic problems and who had not undergone hysterectomy. Participants were asked about symptoms, attitudes, health-related quality of life, sexual functioning, and treatment satisfaction. Preference for current health was measured using the time tradeoff metric, which asked respondents to estimate the number of years of life they would be willing to trade off to not have a uterine condition. Multivariable logistic regression was used to identify determinants of treatment satisfaction. RESULTS: Most (82.7%) participants reported a complete lack of or only partial symptom resolution, and 42.3% reported that their pelvic problems interfered with their ability to have and enjoy sex. Mean Short Form-12 Physical (43-49) and Mental (41-44) Component Summary scores were substantially lower than population norms for women aged 40-49 years. Mean current health time tradeoff scores ranged from 0.78 to 0.88. Satisfaction with Western medicines ranged from 31.3% (progestin intrauterine device) to 58.2% (opiates) and with uterine-preserving surgery from 20.0% (dilation and curettage) to 51.0% (myomectomy); 27.7 % of the women who used acupuncture were satisfied. Participants with lower educational attainment, greater symptom resolution, and less interference of pelvic problems with sex were more likely to be satisfied. CONCLUSION: Noncancerous pelvic problems are associated with serious decrements in health-related quality of life and sexual functioning and low rates of treatment satisfaction. LEVEL OF EVIDENCE: II.

Association of antihypertensive therapy and diastolic hypotension in chronic kidney disease.

The extent to which chronic kidney disease (CKD) affects achievement of blood pressure targets is not comprehensively understood. We evaluated the effects of CKD (estimated glomerular filtration rate: <60 mL/min per 1.73 m(2)) on achievement of blood pressure control (nondiabetic: <140/90 mm Hg; diabetic: <130/85 mm Hg) using data from the Guidelines for Drug Therapy of Hypertension Trial. This 15-month study obtained outpatient blood pressures from 3 Veteran's Affairs institutions. Among 9985 subjects with hypertension, we evaluated the association of CKD with achieved control and antihypertensive medication use. We also explored the association between the number of antihypertensives and systolic, diastolic, and pulse pressure. After 15 months, 41% of participants met blood pressure targets. CKD was not associated with control (adjusted odds ratio: 1.04; 95% CI: 0.93 to 1.15). However, CKD was associated with higher odds of use of >or=3 medications among nondiabetic subjects (odds ratio: 1.46; 95% CI: 1.25 to 1.71) and diabetic subjects (odds ratio: 1.40; 95% CI: 1.17 to 1.66). A significant interaction was observed between CKD and the number of antihypertensives as determinants of diastolic and pulse pressures. Among non-CKD participants, a greater number of antihypertensives (0 compared with 4) was associated with wider pulse pressure (Delta5.2 mm Hg; P<0.001), mainly because of higher systolic pressures (Delta3.6 mm Hg; P=0.001). Among participants with CKD, although greater numbers of antihypertensives were associated with even wider pulse pressures (Delta8.3 mm Hg; P<0.001), this was primarily because of lower diastolic pressures (Delta4.8 mm Hg; P<0.01). Among participants with CKD, greater use of antihypertensives was associated with lower diastolic pressures. Given recent evidence suggesting adverse effects of diastolic hypotension, these results suggest potential risks in patients with CKD from aggressive attempts to control systolic blood pressure.

Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels.

Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, we genotyped 1,343 single-nucleotide polymorphisms (SNPs) in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, we found a significant association of interleukin 6 soluble receptor (IL-6 SR) with European ancestry on chromosome 1 (LOD 4.59), in a region that includes the gene for this receptor (IL-6R). Genotyping 19 SNPs showed that the effect is largely explained by an allele at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL-6 SR in a Japanese cohort. We replicate this association (P<<1.0x10-12) and also demonstrate a new association with circulating levels of a different molecule, IL-6 (P<3.4x10-5). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P<<1.0x10-12 for IL-6 SR, and P<2.0x10-9 for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant.

Concordance of chart abstraction and patient recall of intrapartum variables up to 53 years later.

OBJECTIVE: The purpose of this study was to determine the concordance of patient recall compared with chart abstraction for distant intrapartum variables and to evaluate predictors of concordance. STUDY DESIGN: A random sample from a cohort of diverse women aged 40-74 years. Intrapartum variables reported by participants were compared with the medical record. Outcomes were assessed for sensitivity, specificity, positive predictive value, and negative predictive value. Multivariate logistic regression was used to determine predictors of concordance of patient recall. RESULTS: Four hundred one births among 178 women were analyzed. Recall of cesarean delivery had the highest concordance (sensitivity, 0.98; specificity, 1.00; positive predictive value, 1.00; negative predictive value, 0.99). Laceration that required repair had the lowest concordance (sensitivity, 0.37; specificity, 0.68; positive predictive value, 0.34; negative predictive value, 0.81). No variables predicted concordance of recall for all variables. CONCLUSION: The concordance of patient recall to chart abstraction for intrapartum variables varies widely, although with a pattern of greater specificity and negative predictive value of recall. This should be kept in mind during patient interviews and in the performance of clinical research.

Genetic admixture, adipocytokines, and adiposity in Black Americans: the Health, Aging, and Body Composition study.

Adipocytokines are a subset of cytokines produced by adipose tissue and are associated with risk of type II diabetes and atherosclerosis. Levels of adipocytokines differ between Black and White Americans, even after adjustment for differences in adiposity, diseases associated with adipocytokines including type 2 diabetes and cardiovascular disease, and general socioeconomic status indicators such as income. We used a series of ancestry informative markers to estimate genetic ancestry in a population-based study of older Black Americans, and examined the association between genetic ancestry and adipocytokines and soluble receptors to help determine which of these may be most amenable to admixture mapping. We typed 35 ancestry informative markers in 1,241 self-reported Black Americans with available DNA from the Health, Aging, and Body Composition (Health ABC) study with available DNA and used a maximum likelihood approach to estimate percent European ancestry. We used linear regression models to determine the association between these adipocytokines and percent ancestry, and staged models to examine whether adiposity or other measures affected the associations of genetic ancestry and adipocytokines. Mean European ancestry was 22.3+/-15.9%. In multivariate adjusted models, the strongest associations observed were between higher European ancestry and interleukin-6 soluble receptor (IL-6 SR), C-reactive protein (CRP), and adiponectin levels, with interleukin-2 soluble receptor (IL-2 SR) and soluble tumor necrosis factor receptor II (TNF-alpha SR II) also showing more modest but significant associations. The association with adiponectin became stronger after adjustment for adiposity. These novel findings suggest that admixture mapping may identify genetic factors influencing the levels of IL-6 SR, CRP, IL-2 SR, and adiponectin.

Endothelin-1 and prevalent coronary heart disease in older men and women (the Rancho Bernardo Study).

Endothelin-1 has been implicated in atherosclerotic and ischemic heart disease. No population-based studies have examined the association of endothelin-1 with coronary heart disease (CHD). We performed a cross-sectional analysis of 961 older women and men. CHD was defined as a history of myocardial infarction, coronary surgery, angina, or major Q-wave abnormality on electrocardiography. We examined the association of endothelin-1 with CHD after adjusting for known risk factors and atherosclerosis measures. A total of 248 women and 156 men had CHD. Median endothelin-1 levels were similar by gender and higher among those with versus those without CHD (3.3 vs 3.1 pg/ml, p <0.001). After adjusting for age, smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypertension, diabetes, alcohol use, exercise, aspirin, cholesterol-lowering medication, and hormone therapy use, endothelin-1 had a stronger association with CHD in women (odds ratio [OR] 3.02, (95% confidence interval 1.43 to 6.37) than in men (OR 1.82, 95% confidence interval 0.74 to 4.51). Age modified the effect of endothelin-1 with CHD in men (OR 0.47 for age <75 years vs 3.84 in men >or=75 years, p = 0.05 for interaction). Further adjustment for ankle-brachial index and carotid intima media thickness did not alter these results. In conclusion, higher endothelin-1 levels are independently associated with CHD in women of all ages and among older men only.

Serum adiponectin and coronary heart disease risk in older Black and White Americans.

CONTEXT: Adiponectin may influence the risk of coronary heart disease (CHD) independently of traditional cardiovascular risk factors. OBJECTIVE: Because body composition and adiponectin levels vary by race, we examined the relationship of adiponectin with prevalent and incident CHD in a cohort of older Black and White adults. DESIGN AND SETTING: We conducted a cross-sectional and prospective cohort study at two U.S. clinical centers. PARTICIPANTS: Participants included 3075 well-functioning adults between ages 70 and 79 yr enrolled in the Health, Aging, and Body Composition study. MAIN OUTCOME MEASURES: Prevalent CHD was defined as history of myocardial infarction, coronary artery bypass graft, percutaneous coronary transluminal angioplasty, angina, or major electrocardiogram abnormalities. After excluding those with prevalent CHD, incident CHD was defined as hospitalized myocardial infarction or CHD death. RESULTS: At baseline, 602 participants (19.6%) had CHD. During 6 yr of follow-up, 262 (10.6%) incident CHD events occurred. Whites had higher median adiponectin than Blacks (12 vs. 8 microg/ml, P < 0.001). Race modified the effect of adiponectin (P for interaction was 0.002 for prevalent CHD, and P = 0.02 for incident CHD). Among Whites, an inverse association of adiponectin with CHD was explained by high-density lipoprotein and glucose. Among Blacks, a doubling of adiponectin was associated with a 40% higher risk of both prevalent CHD (odds ratio, 1.41; 95% confidence interval, 1.11-1.78) and incident CHD (hazards ratio, 1.37; 95% confidence interval, 1.01-1.87) after adjusting for explanatory variables. CONCLUSION: High circulating concentrations of adiponectin were associated with higher risk of CHD in older Blacks, even accounting for traditional CHD risk factors.

Unequal placental sharing and birth weight discordance in monochorionic diamniotic twins.

OBJECTIVE: The purpose of this study was to define the association between unequal placental sharing and birth weight discordance in monochorionic/diamniotic twin pregnancies. STUDY DESIGN: The study comprised a prospective cohort of monochorionic/diamniotic twin pregnancies who were delivered in Kaiser Permanente-Northern California, 1997-2003. Dye injection studies of fresh postpartum placentas were performed. Placental sharing, cord insertion combinations, vascular anastomoses, gestational age, and birth weights were recorded. Statistical comparisons of birth weight and gestational age were made with the Student t test. Rates of birth weight discordance were compared with the chi-square test. Multivariate logistic regression models analyzed the relationship between variables of interest. RESULTS: Mean birth weights for larger and smaller twins were 2400 g and 2109 g, respectively. Twenty-two percent of the monochorionic/diamniotic twin pairs had birth weight discordance > or = 20%, and 8% of these pairs had twin-twin transfusion syndrome. Monochorionic/diamniotic twin pairs with unequal placental sharing had a 9.8 times greater likelihood of birth weight discordance (95% CI, 5.4-17.9) as compared with those pairs with equal placental sharing. CONCLUSION: Unequal placental sharing is a significant risk factor for birth weight discordance in monochorionic/diamniotic twins. Antenatal diagnosis of unequal placental sharing would enable improved counseling in the setting of monochorionic/diamniotic twins.

Sexual activity and function in middle-aged and older women.

OBJECTIVE: Data on the sexual activity of middle-aged and older women are scant and vary widely. This analysis estimates the prevalence and predictors of sexual activity and function in a diverse group of women aged 40-69 years. METHODS: The Reproductive Risk Factors for Incontinence Study at Kaiser (RRISK) was a population-based study of 2,109 women aged 40-69 years who were randomly selected from long-term Kaiser Permanente members. Women completed self-report questionnaires on sexual activity, comorbidities, and general quality of life. Logistic and linear regression and proportional odds models were used when appropriate to identify correlates of sexual activity, frequency, satisfaction, and dysfunction. RESULTS: Mean age was 55.9 (+/- 8) years and nearly three fourths of the women were sexually active. Of the sexually active women, 60% had sexual activity at least monthly, approximately two thirds were at least somewhat satisfied, and 33% reported a problem in one or more domains. Monthly or more frequent sexual activity was associated with younger age, higher income, being in a significant relationship, a history of moderate alcohol use, and lower body mass index (BMI) (all P < .05). Satisfaction with sexual activity was associated with African-American race, lower BMI, and higher mental health score (all P < .05). More sexual dysfunction was associated with having a college degree or greater, poor health, being in a significant relationship, and a low mental health score (all P < .05). CONCLUSION: Middle-aged and older women engage in satisfying sexual activity, and one third reported problems with sexual function. Demographic factors as well as some issues associated with aging can adversely affect sexual frequency, satisfaction, and function. LEVEL OF EVIDENCE: II-3.

Adipocytokines and incident diabetes mellitus in older adults: the independent effect of plasminogen activator inhibitor 1.

BACKGROUND: Adipose tissue produces "adipocytokines" of uncertain clinical significance. METHODS: We analyzed the relationships among adiposity, adipocytokines, glycemia, and incident diabetes mellitus in 2356 white and black adults aged 70 to 79 years in the Health, Aging, and Body Composition Study who did not have diabetes at baseline. We measured the levels of adipocytokines adiponectin, leptin, interleukin 6, tumor necrosis factor alpha, and plasminogen activator inhibitor 1. Regional fat area was determined by means of computed tomography. New diabetes was defined as a self-reported diagnosis of diabetes or as a fasting plasma glucose level of 126 mg/dL or greater (>/=7.0 mmol/L) at the second, fourth, or sixth annual examination. RESULTS: A total of 143 participants (14.1 cases per 1000 person-years) developed diabetes across 5 years. Visceral fat area (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.10-1.60 per standard deviation increase) and body mass index (white individuals: OR, 1.65; 95% CI, 1.26-2.15 per standard deviation increase; black individuals: OR, 1.22; 95% CI, 0.99-1.51 per standard deviation increase) independently predicted incident diabetes. Adiponectin, leptin, and plasminogen activator inhibitor 1 attenuated the relationship between adiposity and diabetes. After controlling for body mass index, visceral fat, fasting glucose, fasting insulin, high-density lipoprotein cholesterol, triglycerides, and hypertension at baseline, plasminogen activator inhibitor 1 was the only adipocytokine independently associated with increased odds of diabetes (OR, 1.35; 95% CI, 1.01-1.81). Fasting glucose level at baseline remained a strong predictor of incident diabetes, whereas associations with body mass index and visceral fat were attenuated. CONCLUSIONS: Adipocytokines and glycemia partially account for the relationship between adiposity and risk of type 2 diabetes due to adiposity. Plasminogen activator inhibitor 1 may be a useful predictor of diabetes in addition to measurements of body fat.

Childhood urinary symptoms predict adult overactive bladder symptoms.

PURPOSE: A relationship between childhood urinary symptoms and adult lower urinary tract symptoms in women is often clinically suspected. In this analysis we investigated the relationship between childhood and adult urinary symptoms in middle-aged women. MATERIALS AND METHODS: A population based cohort of 2,109 women 40 to 69 years old who were members of a large health maintenance organization was randomly selected from age and race strata. Through self-reported questionnaires, women recalled a childhood history of and current urinary lower urinary tract symptoms, including frequent daytime urination, nocturia, urinary incontinence, nocturnal enuresis and UTIs. Current incontinence was also classified as urge or stress incontinence. Multivariate analysis was used to evaluate the association between childhood and current lower urinary tract symptoms controlling for age, race, hysterectomy status, parity, oral estrogen use, body mass index and diabetes. RESULTS: Women who reported childhood daytime frequency were more likely to report adult urgency (OR 1.9, 95% CI 1.3-2.6, p < 0.001). Frequent nocturia in childhood was strongly associated with adult nocturia (OR 2.3, 95% CI 1.5-3.5, p < 0.001). Childhood daytime incontinence was associated with adult urge incontinence (OR 2.6, 95% CI 1.1-5.9, p < 0.05), as was childhood nocturnal enuresis (OR 2.7, CI 1.3-5.5, p < 0.01). A history of more than 1 childhood UTI was associated with adult UTIs (OR 2.6, 95% CI 1.5-4.5, p < 0.001). CONCLUSIONS: Childhood urinary symptoms and UTIs were significantly associated with adult overactive bladder symptoms. There is a need to investigate the significance of childhood symptoms as predictors of eventual adult disorders to determine whether treatment of childhood symptoms will alter the prevalence of eventual adult disorders, and if such a history should alter clinical care of the older adult with OAB symptoms.

Differences in prevalence of urinary incontinence by race/ethnicity.

PURPOSE: We compared the prevalence of urinary incontinence by type among white, black, Hispanic and Asian-American women. MATERIALS AND METHODS: The RRISK is a population based cohort study of 2,109 randomly selected middle-aged and older women. Incontinence and other variables were assessed by self-report questionnaires and in person interviews. Labor and delivery and surgical data were abstracted from medical records archived since 1946. Logistic regression was used to estimate the OR with 95% CIs for incontinence while adjusting for covariates. RESULTS: The age adjusted prevalence of weekly incontinence was highest among Hispanic women, followed by white, black and Asian-American women (36%, 30%, 25% and 19%, respectively, p <0.001). Type of incontinence also differed among groups, with weekly stress incontinence prevalence being 18%, 15%, 8% and 8% (p <0.001), and weekly urge incontinence prevalence being 10%, 9%, 14% and 7% (p <0.001). After adjustment for age, parity, hysterectomy, estrogen use, body mass, menopausal status and diabetes, the risk of stress incontinence remained significantly lower in black (adjusted OR 0.36, 95% CI 0.23-0.57) and Asian-American (adjusted OR 0.54, 95% CI 0.34-0.86) women compared to white women. In contrast, the risk of urge incontinence was similar in black (adjusted OR 1.19, 95% CI 0.79-1.81) and Asian-American (adjusted OR 0.86, 95% CI 0.52-1.43) women compared to white women. CONCLUSIONS: Significant differences in the adjusted risk of stress incontinence among Hispanic, white, black and Asian-American women suggest the presence of additional, as yet unrecognized, risk or protective factors for stress incontinence.

Cystatin C and mortality risk in the elderly: the health, aging, and body composition study.

Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-alpha), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, -1.0 (referent); quintile 2, -1.74 (1.21 to 2.50); quintile 3, -1.51 (1.05 to 2.18); quintile 4, -1.49 (1.04 to 2.13); and quintile 5, -2.18 (1.53 to 3.10). These associations did not differ by gender or race. Results were consistent for cardiovascular and other-cause mortality, but not cancer mortality. Creatinine quintiles were not associated with mortality after multivariate adjustment (HR: 1.0 [referent], 1.00 [0.72 to 1.39], 0.95 [0.68 to 1.32], 1.11 [0.79 to 1.57], 1.16 [0.86 to 1.58]). Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine.

Predicting the development of diabetes in older adults: the derivation and validation of a prediction rule.

OBJECTIVE: To create a simple prediction rule that could perform as well as the 2-h postchallenge plasma glucose (PCPG) test to predict those at risk for diabetes. We created a prediction rule in one sample and prospectively validated it for incident diabetes in a separate cohort. RESEARCH DESIGN AND METHODS: A cross-sectional analysis with data from the Rancho Bernardo Study (age 67 +/- 11 years) to derive a rule predicting abnormal PCPG >/=140 mg/dl, using demographic, clinical, and laboratory data of nondiabetic participants with fasting plasma glucose (FPG) <126 mg/dl. Data from the Health, Aging and Body Composition study (age 74 +/- 3 years) were used to prospectively validate this rule for incident diabetes and compare it with the predictive ability of the PCPG test. RESULTS: Of 1,549 RBS participants, 514 (33%) had PCPG >/=140 mg/dl. Female sex, age, triglycerides, and FPG were most significantly associated with abnormal PCPG. Based on standardized beta-coefficients, we allotted 1 point for female sex, triglycerides >/=150 mg/dl, or FPG 95-104 mg/dl. Age >/=70 years or FPG 105-115 mg/dl were given 2 points, and FPG 116-125 mg/dl received 3 points. In the validation cohort, this simple prediction rule was as good as the 2-h PCPG test for predicting incident diabetes (C-statistic: 0.71 for both). CONCLUSIONS: Advanced age, female sex, FPG, and triglycerides were able to predict adults at risk for diabetes equally well as the 2-h PCPG test. Using this rule, clinicians may better identify older persons who should receive intensive lifestyle intervention to prevent type 2 diabetes.