Nawar Shara

Predictors of highly prevalent brain ischemia in intracerebral hemorrhage

This study was undertaken to determine the prevalence, characteristics, risk factors, and temporal profile of concurrent ischemic lesions in patients with acute primary intracerebral hemorrhage (ICH).

Vascular Biomarkers in the Prediction of Clinical Cardiovascular Disease: The Strong Heart Study

We compared the ability of separately measured intimal-medial thickness and atherosclerotic plaque to predict incident cardiovascular disease. American Indian men and women from the Strong Heart Study who were free of cardiovascular disease were evaluated with carotid ultrasound and cardiovascular disease risk factor assessment. End-diastolic intimal-medial thickness of the common carotid arteries was measured and averaged. Arterial mass (cross-sectional area) was calculated from intimal-medial thickness and end-diastolic diameter. Atherosclerosis was defined by focal plaque (discrete thickening >50% relative to the adjacent wall) and the number of carotid segments containing plaque (plaque score); 2441 participants (age 63±8 years) were followed-up for a mean of 7.7±2.8 years, during which time 495 experienced incident cardiovascular disease events. Time-to-event analyses were performed in groups stratified according to diabetes and hypertension status. Cardiovascular disease events were predicted by presence and extent of atherosclerosis in all groups; intima-medial thickness and arterial mass were only associated with outcomes when neither hypertension nor diabetes was present. Unequivocal evidence of atherosclerosis (plaque) and its extent (plaque score) are independently associated with incident cardiovascular disease events in individuals without preexisting cardiovascular disease regardless of diabetes and hypertension status. Hypertension-related increases in intima-media thickness and arterial mass appear to limit their use as measures of early or diffuse atherosclerosis and, hence, association with cardiovascular disease outcomes. These findings support the utility of separate assessment of focal atherosclerosis and intimal-medial thickness in epidemiological studies, trials, and risk stratification protocols.

Incidence rates and predictors of diabetes in those with prediabetes: the Strong Heart Study.

The association between prediabetes as currently defined and incident diabetes in populations with widespread obesity, insulin resistance syndrome, and diabetes is not well defined. In this article, diabetes risk factors and incidence rates in American Indians (AI) with prediabetes are examined.

Association of Chronic Kidney Disease With Cerebral Microbleeds in Patients With Primary Intracerebral Hemorrhage

Background and Purpose— To investigate the relationship between chronic kidney disease (CKD) and MRI-defined cerebral microbleeds (CMB), a harbinger of future intracerebral hemorrhage (ICH), among patients with a recent history of primary ICH. Methods— Using data from a predominantly black cohort of patients with a recent ICH-enrolled in an observational study between September 2007 and June 2011, we evaluated the association between CKD (defined as estimated low glomerular filtration rate<60 mL/min per 1.73 m2) and CMB on gradient-echo MRI. Multivariable models were generated to determine the contribution of CKD to the presence, number, and location of CMB. Results— Of 197 subjects with imaging data, mean age was 59 years, 48% were women, 73% were black, 114 (58%) had ≥1 CMBs, and 52 (26%) had CKD. Overall, CKD was associated with presence of CMB (adjusted odds ratio, 2.70; 95% confidence interval [CI], 1.10–6.59) and number of CMB (adjusted relative risk, 2.04; 95% CI, 1.27–3.27). CKD was associated with CMB presence (adjusted odds ratio, 3.44; 95% CI, 1.64–7.24) and number (adjusted relative risk, 2.46; 95% CI, 1.11–5.42) in black patients, but not CMB presence (adjusted odds ratio, 3.00; 95% CI, 0.61–14.86) or number (adjusted relative risk, 1.03; 95% CI: 0.22–4.89) in non-Hispanic white patients (interactions by race were statistically not significant). Conclusions— CKD is associated with a greater presence and number of CMB in ICH patients, particularly in patients of black race. Future studies should assess whether low estimated glomerular filtration rate may be a CMB risk marker or potential therapeutic target for mitigating the development of CMB.

Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population

CONTEXT The significance of studies suggesting an increased risk of bone fragility fractures with hyponatremia through mechanisms of induced bone loss and increased falls has not been demonstrated in large patient populations with different types of hyponatremia. OBJECTIVE This matched case-control study evaluated the effect of hyponatremia on osteoporosis and fragility fractures in a patient population of more than 2.9 million. DESIGN, SETTING, AND PARTICIPANTS Osteoporosis (n = 30 517) and fragility fracture (n = 46 256) cases from the MedStar Health database were matched on age, sex, race, and patient record length with controls without osteoporosis (n = 30 517) and without fragility fractures (n = 46 256), respectively. Cases without matched controls or serum sodium (Na(+)) data or with Na(+) with a same-day blood glucose greater than 200 mg/dL were excluded. MAIN OUTCOME MEASURES Incidence of diagnosis of osteoporosis and fragility fractures of the upper or lower extremity, pelvis, and vertebrae were the outcome measures. RESULTS Multivariate conditional logistic regression models demonstrated that hyponatremia was associated with osteoporosis and/or fragility fractures, including chronic [osteoporosis: odds ratio (OR) 3.97, 95% confidence interval (CI) 3.59-4.39; fracture: OR 4.61, 95% CI 4.15-5.11], recent (osteoporosis: OR 3.06, 95% CI 2.81-3.33; fracture: OR 3.05, 95% CI 2.83-3.29), and combined chronic and recent hyponatremia (osteoporosis: OR 12.09, 95% CI 9.34-15.66; fracture: OR 11.21, 95% CI 8.81-14.26). Odds of osteoporosis or fragility fracture increased incrementally with categorical decrease in median serum Na(+). CONCLUSIONS These analyses support the hypothesis that hyponatremia is a risk factor for osteoporosis and fracture. Additional studies are required to evaluate whether correction of hyponatremia will improve patient outcomes.

Racial Disparities in Tissue Plasminogen Activator Treatment Rate for Stroke A Population-Based Study

Background and Purpose— Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. Methods— Systematic chart abstraction was performed on consecutive hospitalized patients with ischemic stroke from all 7 acute care hospitals in the District of Columbia from February 1, 2008, to January 31, 2009. Results— Of 1044 patients with ischemic stroke, 74% were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were one third less likely than whites to receive intravenous tPA (3% versus 10%, P<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA-eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with intravenous tPA than whites (27% versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% versus 76%, P=0.62). Conclusions— In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with intravenous tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

The association of genetic variants of type 2 diabetes with kidney function

Type 2 diabetes is highly prevalent and is the major cause of progressive chronic kidney disease in American Indians. Genome wide association studies identified several loci associated with diabetes but their impact on susceptibility to diabetic complications is unknown. To measure this we studied the association of 18 type 2 diabetes genome wide association single nucleotide polymorphisms (SNPs) with the estimated glomerular filtration rate (eGFR) (MDRD equation) and urine albumin to creatinine ratio in 6,958 individuals in the Strong Heart Study family and cohort participants. Center specific residuals of eGFR and the log urine albumin to creatinine ratio, obtained from linear regression models adjusted for age, sex and body mass index, were regressed onto SNP dosage using variance component in family data and linear regression models in unrelated individuals. Estimates were then combined across centers. Four diabetic loci were associated with eGFR and one locus with the urine albumin to creatinine ratio. A SNP in the WFS1 gene (rs10010131) was associated with higher eGFR in younger individuals and with increased albuminuria. The SNPs of the FTO, KCNJ11 and TCF7L2 genes were associated with lower eGFR, not albuminuria, and were not significant in prospective analyses. Our findings suggest a shared genetic risk for type 2 diabetes, its kidney complications, and a potential role for WFS1 in early onset diabetic nephropathy in American Indian populations.

A Longitudinal Study of Risk Factors for Incident Albuminuria in Diabetic American Indians: The Strong Heart Study

BACKGROUND There have been no studies that use longitudinal data with more than 2 measurements and methods of longitudinal data analysis to identify risk factors for incident albuminuria over time more effectively. STUDY DESIGN Longitudinal study. SETTINGS & PARTICIPANTS A subgroup of participants in the Strong Heart Study, a population-based sample of American Indians, in central Arizona, Oklahoma, and North and South Dakota. Participants with diabetes without albuminuria were followed up for a mean of 4 years. PREDICTORS Age, sex, study center, high-density lipoprotein and low-density lipoprotein cholesterol levels, triglyceride level, body mass index, systolic blood pressure, use of antihypertensive medication, smoking, hemoglobin A(1c) level, fasting glucose level, type of diabetes therapy, diabetes duration, plasma creatinine level, and urinary albumin-creatinine ratio (UACR). OUTCOMES & MEASUREMENTS Albuminuria was defined as UACR of 30 mg/g or greater. Urine creatinine and albumin were measured by using the picric acid method and a sensitive nephelometric technique, respectively. RESULTS Of 750 and 568 participants with diabetes without albuminuria and with normal plasma creatinine levels at the first and second examinations, 246 and 132 developed albuminuria by the second and third examinations, respectively. Incident albuminuria was predicted by baseline UACR, fasting glucose level, systolic blood pressure, plasma creatinine level, study center, current smoking, and use of angiotensin-converting enzyme inhibitors and antidiabetic medications. UACR of 10 to 30 mg/g increased the odds of developing albuminuria 2.7-fold compared with UACR less than 5 mg/g. LIMITATIONS Single random morning urine specimen. CONCLUSIONS Many risk factors identified for incident albuminuria can be modified. Control of blood pressure and glucose level, smoking cessation, and use of angiotensin-converting enzyme inhibitors may reduce the incidence of albuminuria.

Dietary Intake of Fiber, Fruit and Vegetables Decreases the Risk of Incident Kidney Stones in Women: A Women's Health Initiative Report

PURPOSE We evaluated the relationship between dietary fiber, fruit and vegetable intake, and the risk of kidney stone formation. MATERIALS AND METHODS Overall 83,922 postmenopausal women from the Womens Health Initiative observational study were included in the analysis and followed prospectively. Cox proportional hazards regression analyses were used to evaluate the associations between total dietary fiber, fruit and vegetable intake, and the risk of incident kidney stone formation, adjusting for nephrolithiasis risk factors (age, race/ethnicity, geographic region, diabetes mellitus, calcium supplementation, hormone therapy use, body mass index and calibrated caloric intake; and dietary water, sodium, animal protein and calcium intake). Women with a history of kidney stones (3,471) were analyzed separately. RESULTS Mean age of the women was 64±7 years, 85% were white and 2,937 (3.5%) experienced a kidney stone in a median followup of 8 years. In women with no history of kidney stones higher total dietary fiber (6% to 26% decreased risk, p <0.001), greater fruit intake (12% to 25% decreased risk, p <0.001) and greater vegetable intake (9% to 22% decreased risk, p=0.002) were associated with a decreased risk of incident kidney stone formation in separate adjusted models. In women with a history of stones there were no significant protective effects of fiber, fruit or vegetable intake on the risk of kidney stone recurrence. CONCLUSIONS Greater dietary intake of fiber, fruits and vegetables was associated with a reduced risk of incident kidney stones in postmenopausal women. The protective effects were independent of other known risk factors for kidney stones. In contrast, there was no reduction in risk in women with a history of stones.

Linkage Analysis of Albuminuria

American Indians have a higher prevalence of albuminuria than the general population, likely resulting from a combination of environmental and genetic risk factors. To localize gene regions influencing variation in urinary albumin-to-creatinine ratio, we performed a linkage analysis and explored gene-by-diabetes, -hypertension, and -obesity interactions in a large cohort of American Indian families. We recruited >3600 individuals from 13 American Indian tribes from three centers (Arizona, North and South Dakota, and Oklahoma). We performed multipoint variance component linkage analysis in each center as well as in the entire cohort after controlling for center effects. We used two modeling strategies: Model 1 incorporated age, gender, and interaction terms; model 2 also controlled for diabetes, BP, body mass index, HDL, LDL, triglycerides, and smoking status. We evaluated interactions with diabetes, hypertension, and obesity using additive, interaction-specific linkage and stratified analyses. Loci suggestive for linkage to urinary albumin-to-creatinine ratio included 1q, 6p, 9q, 18q, and 20p. Gene-by-diabetes interaction was present with a quantitative trait locus specific to the diabetic stratum in the Dakotas isolated on 18q21.2 to 21.3 using model 1 (logarithm of odds = 3.3). Gene-by-hypertension interaction was present with quantitative trait loci specific to the hypertensive stratum in the Dakotas on 7q21.11 using model 1 (logarithm of odds = 3.4) and 10q25.1 using model 2 (logarithm of odds = 3.3). These loci replicate findings from multiple other genome scans of kidney disease phenotypes with distinct populations and are worthy of further study.