Jaclyn Bergstrom

Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.

BACKGROUND Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD).

Cardiovascular death and the metabolic syndrome: role of adiposity-signaling hormones and inflammatory markers.

OBJECTIVE— Levels of adiposity-signaling hormones and inflammatory markers are less favorable in individuals with the metabolic syndrome; their role in the association between the metabolic syndrome and cardiovascular mortality remains unclear. RESEARCH DESIGN AND METHODS— We conducted a prospective study of 977 men and 1,141 women aged 40–94 years in 1984–1987, followed for mortality for a maximum of 20 years. Adiponectin, leptin, ghrelin, interleukin-6 (IL-6), C-reactive protein (CRP), and Adult Treatment Panel III–defined metabolic syndrome components were measured in fasting blood samples obtained in 1984–1987. Cox-proportional hazards models were used in survival analyses. RESULTS— The age- and sex-adjusted hazard ratio (HR) (95% CI) for coronary heart disease (CHD) mortality associated with the metabolic syndrome was 1.65 (1.25–2.18) (P < 0.001); this association did not differ significantly by sex, age, or diabetic status (P > 0.2 for each interaction). The association between the metabolic syndrome and CHD mortality was not materially changed after adjustment for adiponectin, leptin, and ghrelin; it was attenuated by 25% after adjustment for IL-6 and 35% after adjustment for CRP. CHD mortality increased linearly with greater levels of IL-6 and CRP (Ptrend < 0.001 for each); the age- and sex-adjusted HRs comparing highest versus lowest quarter were 3.0 (1.87–4.89) for IL-6 and 2.1 (1.41–3.21) for CRP. IL-6, but not CRP, remained a significant predictor of CHD mortality in models including both inflammatory markers and the metabolic syndrome. CONCLUSIONS— Adiposity-signaling hormones and inflammatory markers explain little to some of the association between the metabolic syndrome and CHD mortality. IL-6 levels predict CHD mortality independently of CRP.

Prevalence and Characteristics of Lower Urinary Tract Symptoms in Men Aged ≥80 Years

OBJECTIVES We analyzed the prevalence and characteristics of lower urinary tract symptoms (LUTS) in community-dwelling men aged 80 years and older. METHODS We administered the American Urological Association Symptom Index (AUA-SI) by mail to 291 surviving community-dwelling male participants in the Rancho Bernardo Study, a prospective, community-based study of aging. We compared the prevalence, severity, and types of LUTS occurring in men who were > or = 80 years to those < 80 years. RESULTS The mean age was 74.6 years (standard deviation [SD] 8.9, range 48.3-97.1). One third of the respondents were > or = 80 years. The mean total AUA-SI score increased steadily by decade of life (P-trend = .002). The prevalence of LUTS was 70% in men > or = 80 years and 56% in men < 80 years (P = .03). Men > or = 80 years had significantly higher mean total AUA-SI (P = .05) and were more likely to complain of incomplete emptying (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.06-4.18, P = .02), frequency (OR 1.83, 95% CI 1.00-3.31, P = .03), urgency (OR 1.76, 95% CI 0.96-3.20, P = .05), and weak stream (OR 1.78, 95% CI 1.01-3.12, P = .03). CONCLUSIONS In this cohort of community-dwelling men, prevalence and severity of LUTS increased into the 10th decade of life. Compared to younger men, men > or = 80 years were more likely to complain of incomplete emptying, frequency, urgency, and weak stream. Further studies of LUTS in older men are needed to better delineate these associations.

Lipids, lipoproteins and the risk of benign prostatic hyperplasia in community-dwelling men

To examine the associations of serum lipids and lipoproteins with benign prostatic hyperplasia (BPH) in community‐dwelling men.

The Associations of Fetuin-A with Subclinical Cardiovascular Disease in Community-Dwelling Persons: the Rancho Bernardo Study

OBJECTIVES The aim of this study was to determine the association of fetuin-A with subclinical cardiovascular disease (CVD) in community-living individuals. BACKGROUND Fetuin-A is a hepatic secretory protein that inhibits arterial calcium deposition in vitro. Lower fetuin-A levels are associated with arterial calcification and death in end-stage renal disease populations. The association of fetuin-A with subclinical CVD in the general population is unknown. METHODS Among 1,375 community-living individuals without prevalent clinical CVD, we measured plasma fetuin-A concentrations. Peripheral arterial disease (PAD) was defined by ankle brachial index <0.90, coronary artery calcification (CAC) was measured by computed tomography, and common and internal intima-media thickness (cIMT) were measured by carotid ultrasound. PAD was measured concurrent with fetuin-A, and CAC and cIMT were measured 4.6 years (mean) later. RESULTS Mean age was 70 ± 11 years, and 64% were women. Fetuin-A levels were inversely associated with CAC severity. When evaluated as CAC categories (0, 1 to 100, 101 to 300, >300) with ordinal logistic regression, each SD higher fetuin-A was associated with 31% lower odds of CAC severity (proportional odds ratio: 0.69; 95% confidence interval: 0.46 to 0.92; p = 0.008) in models adjusted for demographic data, lifestyle factors, traditional CVD risk factors, and kidney function. In contrast, no association of fetuin-A was observed with PAD or high common or internal cIMT in adjusted models. CONCLUSIONS Lower fetuin-A levels are independently associated with greater CAC severity but not PAD or cIMT. If confirmed, fetuin-A might mark calcium deposition within the vasculature but not atherosclerosis per se.

Serum sex hormones and the 20‐year risk of lower urinary tract symptoms in community‐dwelling older men

Study Type – Prognosis (inception cohort)
Level of Evidence 2b

Metabolic Syndrome and 16-Year Cognitive Decline in Community-Dwelling Older Adults

PURPOSE To determine whether metabolic syndrome is associated with accelerated cognitive decline in community-dwelling older adults. METHODS A longitudinal study of 993 adults (mean 66.8 ± 8.7 years) from the Rancho Bernardo Study. Metabolic syndrome components, defined by 2001 NCEP-ATP III criteria, were measured in 1984-1987. Cognitive function was first assessed in 1988-1992. Cognitive assessments were repeated approximately every 4 years, for a maximum 16-year follow-up. Mixed-effects models examined longitudinal rate of cognitive decline by metabolic syndrome status, controlling for factors plausibly associated with cognitive function (diabetes, inflammation). RESULTS Metabolic syndrome was more common in men than women (14% vs. 9%, p = .01). In women, metabolic syndrome was associated with greater executive function and long-term memory decline. These associations did not differ by inflammatory biomarker levels. Diabetes did not alter the association of metabolic syndrome with long-term recall but modified the association with executive function: metabolic syndrome was associated with accelerated executive function decline in diabetic women only. Metabolic syndrome was not related to rate of decline on any cognitive measure in men. CONCLUSIONS Metabolic syndrome was a risk factor for accelerated cognitive decline, but only in women. Prevention of metabolic syndrome may aid in maintenance of cognitive function with age.

Diabetes and Coronary Heart Disease in Filipino-American Women Role of growth and life-course socioeconomic factors

OBJECTIVE—To investigate associations between adult markers of childhood growth and the prevalence of diabetes and coronary heart disease (CHD) in Filipino-American women and to determine the role of social and educational differences, including the influence of social mobility between childhood and adulthood. RESEARCH DESIGN AND METHODS—Socioeconomic disadvantage and poor infant growth, resulting in short leg length, may contribute to the dramatically increased risk of diabetes and CHD in Filipino-American women, but this has not been investigated. This study is a cross-sectional study of 389 Filipino-American women (age 58.7 ± 9.4 years [mean ± SD]). Diabetes was defined by 1999 World Health Organization criteria and CHD by ischemic electrocardiogram changes, Rose angina, a history of myocardial infarction, or revascularization surgery. A score of social mobility (0–4) was calculated by summarizing childhood and adult financial circumstances. RESULTS—Diabetes prevalence (31.4%) was not associated with measures of growth but was significantly lower in women with greater education, childhood and adult income, or social mobility score. Compared with Filipinas who were poorest in childhood and adulthood, respective odds ratios (95% CI) for diabetes were 0.55 (0.18–1.68), 0.19 (0.06–0.62), and 0.11 (0.03–0.42), down to 0.07 (0.01–0.51) in the most advantaged women (P < 0.0001). Family history of diabetes [5.14 (2.72–9.70)] and larger waist [1.07 per cm (1.03–1.10)] were also significant predictors in multiple adjusted models. In contrast, CHD prevalence (22.4%) was most strongly associated with leg length, but not trunk length; compared with individuals with the shortest legs, respective odds ratios (95% CI) for CHD were 0.60 (0.31–1.19), 0.53 (0.26–1.05), and 0.44 (0.22–0.91) in the tallest group, in age- (Ptrend = 0.02) and multiple-adjusted models (Ptrend = 0.01). CONCLUSIONS—Socioeconomic disadvantage contributes to the high prevalence of diabetes in Filipinas. Factors limiting early growth of the legs may increase the risk of CHD in this comparatively short population.

Point-of-care musculoskeletal ultrasound is critical for the diagnosis of hemarthroses, inflammation and soft tissue abnormalities in adult patients with painful haemophilic arthropathy

We previously demonstrated in adult patients with haemophilia (PWH) that hemarthrosis is present in only ~1/3rd of acutely painful joints by using point‐of‐care‐musculoskeletal ultrasound (MSKUS). Therefore, other unrecognized tissue abnormalities must contribute to pain. Using high resolution MSKUS, employing grey scale and power Doppler, we sought to retrospectively (i) investigate soft tissue abnormalities in painful haemophilic joints and (ii) to determine to what extent MSKUS findings, functional or radiographic joint scores correlate with biomarkers of inflammation in PWH. Findings were correlated with Hemophilia Joint Health Scores (HJHS), Pettersson scores, high sensitivity C‐reactive protein and von Willebrand factor activity and antigen levels. A total of 65 MSKUS examinations for acute and chronic joint pains were performed for 34 adult haemophilia patients, mostly for chronic joint pains (72.3%). The most prominent findings (66.5%) pertained to inflammatory soft tissue changes including synovitis, tendinitis, enthesitis, bursitis and fat pad inflammation. Effusions were present in 55.5% and 46.8% of MSKUS performed for acute and chronic pain, respectively. Of those, 90.0% were bloody during acute and 47.6% during persistent pains. While inflammatory biomarkers correlated well with overall HJHS and total Pettersson scores (P < 0.05), they did not differ between those patients with synovitis and those without. MSKUS is emerging as an important modality to diagnose treatable musculoskeletal abnormalities contributing to pain in haemophilic arthropathy, and therefore seems critical for a personalized approach to haemophilia care. The role of biomarkers in this setting remains less clear and requires further investigation.

Global Cardiovascular and Renal Outcomes of Reduced GFR

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.