Mahboob Rahman

Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective: To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Insights into end-stage renal disease have emerged from many investigations but less is known about the epidemiology of chronic renal insufficiency (CRI) and its relationship to cardiovascular disease (CVD). The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for progression of CRI and CVD among CRI patients and develop models to identify high-risk subgroups, informing future treatment trials, and increasing application of preventive therapies. CRIC will enroll approximately 3000 individuals at seven sites and follow participants for up to 5 yr. CRIC will include a racially and ethnically diverse group of adults aged 21 to 74 yr with a broad spectrum of renal disease severity, half of whom have diagnosed diabetes mellitus. CRIC will exclude subjects with polycystic kidney disease and those on active immunosuppression for glomerulonephritis. Subjects will undergo extensive clinical evaluation at baseline and at annual clinic visits and via telephone at 6 mo intervals. Data on quality of life, dietary assessment, physical activity, health behaviors, depression, cognitive function, health care resource utilization, as well as blood and urine specimens will be collected annually. (125)I-iothalamate clearances and CVD evaluations including a 12-lead surface electrocardiogram, an echocardiogram, and coronary electron beam or spiral CT will be performed serially. Analyses planned in CRIC will provide important information on potential risk factors for progressive CRI and CVD. Insights from CRIC should lead to the formulation of hypotheses regarding therapy that will serve as the basis for targeted interventional trials focused on reducing the burden of CRI and CVD.

BACKGROUND AND OBJECTIVES: The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with CKD. We examined baseline demographic and clinical characteristics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seven clinical centers recruited adults who were aged 21 to 74 yr and had CKD using age-based estimated GFR (eGFR) inclusion criteria. At baseline, blood and urine specimens were collected and information regarding health behaviors, diet, quality of life, and functional status was obtained. GFR was measured using radiolabeled iothalamate in one third of participants. RESULTS: A total of 3612 participants were enrolled with mean age +/- SD of 58.2 +/- 11.0 yr; 46% were women, and 47% had diabetes. Overall, 45% were non-Hispanic white, 46% were non-Hispanic black, and 5% were Hispanic. Eighty-six percent reported hypertension, 22% coronary disease, and 10% heart failure. Mean body mass index was 32.1 +/- 7.9 kg/m(2), and 47% had a BP >130/80 mmHg. Mean eGFR was 43.4 +/- 13.5 ml/min per 1.73 m(2), and median (interquartile range) protein excretion was 0.17 g/24 h (0.07 to 0.81 g/24 h). Lower eGFR was associated with older age, lower socioeconomic and educational level, cigarette smoking, self-reported CVD, peripheral arterial disease, and elevated BP. CONCLUSIONS: Lower level of eGFR was associated with a greater burden of CVD as well as lower socioeconomic and educational status. Long-term follow-up of participants will provide critical insights into the epidemiology of CKD and its relationship to adverse outcomes.

Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease. Performance of the Modification of Diet in Renal Disease (MDRD) Study equation varies substantially among populations. To describe the performance of the equation in a large, diverse population, estimated GFR (eGFR) was compared to measured GFR (mGFR) in a cross-sectional analysis of 5504 participants in 10 studies that included measurements of standardized serum creatinine and urinary clearance of iothalamate. At eGFR <60 ml/min per 1.73 m(2), the MDRD Study equation had lower bias and higher precision than at eGFR > or =60 ml/min per 1.73 m(2). The accuracy of the equation, measured by the percent of estimates that fell within 30% of mGFR, was similar for eGFR values above or below 60 ml/min per 1.73 m(2) (82% and 84%, respectively). Differences in performance among subgroups defined by age, sex, race, diabetes, transplant status, and body mass index were small when eGFR was <60 ml/min per 1.73 m(2). The MDRD Study equation therefore provides unbiased and reasonably accurate estimates across a wide range of subgroups when eGFR is <60 ml/min per 1.73 m(2). In individual patients, interpretation of GFR estimates near 60 ml/min per 1.73 m(2) should be interpreted with caution to avoid misclassification of chronic kidney disease in the context of the clinical setting.

OBJECTIVE: Intrauterine and neonatal growth failure of very low birth weight (VLBW; <1500 g) infants may influence adult growth attainment and have long-term implications for adult health. As part of a longitudinal study of VLBW infants, we sought to examine gender-specific changes in growth from birth to 20 years old and to identify the correlates of growth attainment at 20 years old. DESIGN, SETTING, PARTICIPANTS: A cohort of 103 male and 92 female VLBW infants who had a mean birth weight of 1189 g and mean gestational age of 29.8 weeks, were born from 1977 through 1979 and treated at Rainbow Babies and Children's Hospital in Cleveland, Ohio, and were free of neurosensory impairment were followed prospectively from birth and compared with a population-based sample of 101 male and 107 female normal birth weight (NBW) controls selected at 8 years old. Maternal sociodemographic status and infant birth and neonatal data did not differ significantly between male and female VLBW subjects. However, male VLBW subjects had significantly higher rates of rehospitalization during infancy than female VLBW (39% vs 21%). At 20 years, their rates of chronic illness were similar (18% vs 24%). MAIN OUTCOME MEASURES: Weight and height z scores were computed at birth, 40 weeks, 8 and 20 months, and 8 and 20 years among the VLBW subjects, and at 8 and 20 years among the NBW controls. Body mass index (BMI) z scores were computed at 8 and 20 years. Among the VLBW subjects, gender-specific longitudinal growth measures were examined at birth, at the expected term date (40 weeks corrected age), and at 8 and 20 months, and 8 and 20 years of age. In addition, we compared the weight, height, and BMI of the VLBW and NBW controls at 8 and 20 years. Predictors of 20-year growth were examined via multivariate analyses. RESULTS: Among the VLBW males, mean weight for age z scores at birth, 40 weeks, and 8 years were -0.7, -1.8, and -0.5; and height for age z scores were -1.2, -2.6, and -0.5, respectively. For VLBW females, mean weight for age z scores were -1.1, -2.0, and -0.2 and height for age z scores were -1.2, -2.4, and -0.2, respectively. At 8 years of age, VLBW males had a significantly lower mean weight, height, and BMI than NBW controls, whereas VLBW females differed significantly from their NBW controls in mean weight and BMI but not in height. Catch-up growth in weight, height, and BMI occurred between 8 and 20 years among VLBW females but not among VLBW males who remained significantly smaller than their controls at 20 years old. At 20 years mean weight of VLBW males was 69 kg versus 80 kg for controls (z score -0.4 vs +0.5); mean height was 174 cm versus 177 cm (z score -0.4 vs +0.03) and mean BMI was 23 versus 26, respectively. For VLBW females, mean weight was 65 kg versus 68 kg for controls (z score +0.3 vs +0.5), mean height was 162 versus 163 cm (z score -0.3 vs -0.1) and mean BMI was 25 versus 25, respectively. Rates of obesity (BMI >30) for VLBW males were 7% compared with 15% for controls and for VLBW females 15% compared with 18% for controls. Age of menarche was 12.4 years for VLBW females and 12.3 years for controls. Nineteen (18%) male and 20 (22%) female VLBW subjects were born small for gestational age (SGA; weight less than -2 standard deviation for gestational age). At 20 years, significantly more SGA than appropriate for gestational age VLBW males remained subnormal (less than -2 standard deviation) in weight (32% vs 6%) and height (21% vs 4%), whereas rates of subnormal growth did not differ significantly between SGA and appropriate for gestational age females (weight 5% vs 1%, height 0% vs 7%). Predictor variables included in the multivariate analyses of 20-year growth attainment were maternal education and height, race, birth weight z score (a measure of intrauterine growth failure), neonatal hospital stay (a measure of neonatal illness), and chronic illness at 20 years. Twenty-year weight was predicted by black race and chronic illness among females. Twenty-year height was predicted by maternal height and birth weight z score among both males and females and by duration of neonatal hospital stay among males only. In a separate model, when we examined the effect of being SGA at birth instead of the effect of birth weight z score, SGA birth was predictive of 20-year height among males but not among females. CONCLUSIONS: VLBW females catch up in growth by 20 years of age whereas VLBW males remain significantly shorter and lighter than controls. Since catch-up growth may be associated with metabolic and cardiovascular risk later in life, these findings may have implications for the future adult health of VLBW survivors.