Advanced glycation end product level, diabetes, and accelerated cognitive aging.

OBJECTIVE: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. METHODS: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of >1.0 SD on each test) was analyzed with logistic regression. RESULTS: Older adults with high pentosidine level had worse baseline DSST score (p=0.05) but not different 3MS score (p=0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall <0.001; DSST 5.9, 7.4, and 4.5 point decline, p=0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio=1.55; 95% confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio=1.62; 95% confidence interval 1.13-2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. CONCLUSION: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes.

Plasma F2-isoprostane level and cognitive function over eight years in non-demented older adults: Findings from the Health ABC Study.

F2-isoprostanes (F2-IsoP) are reportedly increased in dementia patients, and are considered a reliable biomarker of oxidation. However, few studies have examined the predictive value of peripheral F2-IsoP levels in non-demented older adults. This study assesses the association between plasma F2-IsoP and change in cognitive function in non-demented elderly over eight years. Plasma F2-IsoP was measured by gas chromatography-mass spectrometry in a biracial cohort of 726 elderly men and women. Digit Symbol Substitution test and the Modified Mini-Mental State Exam were administered over time. No association was found between F2-IsoP tertile and baseline or change (slope) in cognitive function over eight years. Plasma F2-IsoP is not a valuable biomarker in predicting cognitive change over years in non-demented older adults.

Executive function, memory, and gait speed decline in well-functioning older adults.

BACKGROUND: In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time. METHODS: Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 ± 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up. RESULTS: Poorer performance in each cognitive task was cross-sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p =.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics. CONCLUSIONS: In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging.

Predictors of maintaining cognitive function in older adults: the Health ABC study.

BACKGROUND: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age. METHODS: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope > or = 0), minor decliners (slope < 0 and > 1 SD below mean), or major decliners (slope < or = 1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner. RESULTS: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55-0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30-2.28), high school education level or greater (OR = 2.75, 95% CI 1.78-4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00-7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06-1.62), and not smoking (OR = 1.84, 95% CI 1.14-2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported. CONCLUSION: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies.

Association of adiponectin with mortality in older adults: the Health, Aging, and Body Composition Study.

AIMS/HYPOTHESIS: Despite inverse associations with insulin resistance and adiposity, adiponectin has been associated with both increased and decreased risk of cardiovascular disease. We examined whether adiponectin is associated with total and cardiovascular mortality in older adults with well-characterised body composition. METHODS: We analysed data from 3,075 well-functioning adults aged 69-79 years at baseline. Mortality data were obtained over 6.6 +/- 1.6 years. We used Cox proportional hazards models adjusting for covariates in stages to examine the association between adiponectin and total and cardiovascular mortality. RESULTS: There were 679 deaths, 36% of which were from cardiovascular disease. Unadjusted levels of adiponectin were not associated with total or cardiovascular mortality. However, after adjusting for sex and race, adiponectin was associated with an increased risk of both total mortality (hazard ratio 1.26, 95% CI 1.15-1.37, per SD) and cardiovascular mortality (hazard ratio 1.35, 95% CI 1.17-1.56, per SD). Further adjustment for study site, smoking, hypertension, diabetes, prevalent heart disease, HDL-cholesterol, LDL-cholesterol, renal function, fasting insulin, triacylglycerol, BMI, visceral fat, thigh intermuscular fat and thigh muscle area did not attenuate this association. This association between adiponectin and increased mortality risk did not vary by sex, race, body composition, diabetes, prevalent cardiovascular disease, smoking or weight loss. CONCLUSIONS/INTERPRETATION: Higher levels of adiponectin were associated with increased risks of total and cardiovascular mortality in this study of older persons.

Location specific radiographic joint space width for osteoarthritis progression.

OBJECTIVE: To establish the performance of location specific computer measures of radiographic joint space width (JSW) compared to measurements of minimum joint space width (mJSW) for the assessment of medial compartment knee osteoarthritis (OA). The study also investigated the most disease-responsive location for measuring medial compartment JSW. METHODS: Serial bilateral Posterior Anterior (PA) conventional radiographs acquired with a fixed flexion protocol were obtained 36 months apart in 118 persons with knee OA participating in the Health, Aging and Body Composition (Health ABC) Study. Measurements of medial compartment mJSW and JSW at seven fixed locations were facilitated by the use of semi-automated software that delineated the femoral and tibial margins of the joint. A human reader operated custom software to verify and correct the software-drawn margins where necessary. Paired images were displayed with the reader blinded to the chronological order. The amount of joint space narrowing was measured and the standardized response mean (SRM) was used as a metric to quantify performance. RESULTS: For all subjects, the mJSW SRM value was 0.42 while, for the most responsive location specific measure of JSW, it was SRM=0.46. For subjects with a Kellgren-Lawrence (KL) score less than or equal to 1, mJSW (SRM=0.40) was more responsive than the new measures (Maximum SRM=0.30). For KL=2or3, SRM=0.49 for mJSW, and SRM=0.74 for the most responsive location specific measure of JSW. Improved responsiveness was observed in the more central portion of the joint on the more diseased knees. CONCLUSIONS: Location specific computer measures of JSW are feasible and potentially provide a superior method to assess radiographic OA for more diseased subjects. This new measure has the potential to improve the power of clinical studies that use a fixed flexion protocol.

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study.

The role of renin-angiotensin system (RAS) genes on the risk of lower extremity arterial disease (LEAD) in elderly people remains unclear. We assessed the relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the angiotensinogen (AGT) gene, and the angiotensin-converting enzyme insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and Body Composition (Health ABC) Study. This analysis included 1228 black and 1306 white men and women whose age ranged between 70 and 79 years at the study enrollment. LEAD was defined as ankle-arm index (AAI) <0.9. Genotype-phenotype associations were estimated by regression analyses with and without adjustment for established cardiovascular disease (CVD) risk factors. The proportion of LEAD was significantly higher in black (21.1%) than that in white elderly people (10.1%, P<0.0001). The distribution of AGT polymorphisms was also significantly different between black and white participants. There was no statistically significant association between the selected RAS genetic variants and LEAD after adjustment for age, antihypertensive medications, lipid-lowering medication, pack-year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent diabetes and coronary heart disease. However, A-T haplotype of G-6A and M235T interacting with homozygous ACE_II (beta=-1.07, P=0.006) and with ACE inhibitors (beta=-1.03, P=0.01) significantly decreased the risk of LEAD in white but not in black participants after adjustment for the selected CVD risk factors. In conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in the white elderly.

Endogenous sex hormone levels and risk of cognitive decline in an older biracial cohort.

BACKGROUND: Older women treated with conjugated estrogens may have an increased risk of dementia, but the effect of naturally occurring sex hormones on cognition is not certain. METHODS: Bioavailable estradiol and free testosterone level were obtained from 792 (55% men, 51% black) participants. We assessed cognition with the Modified Mini-Mental State Examination (3MS), Selective Reminding Test (SRT) and CLOX 1 at baseline and 2 years later. RESULTS: Women in the lowest estradiol tertile were more likely than those in the highest tertile to decline (> or = 1.0 S.D. of change) on 3MS (25% versus 9%, adjusted odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.6-9.6) and on SRT (28% versus 12%, adjusted OR [95% CI] = 3.3 [1.4-7.9]) but not CLOX 1. There was a borderline association between low estradiol tertile and decline on SRT in men (22% versus 14%, adjusted OR [95% CI] = 1.9 [0.9-3.9]). Testosterone level was not associated with decline in cognition in either men or women. Findings did not differ by race. CONCLUSIONS: Older women with low estradiol levels were more likely to experience decline in global cognitive function and verbal memory, and a similar trend was observed for verbal memory in men. This supports the hypothesis that endogenous sex hormones may play an important role in the maintenance of cognitive function in older adults.

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects.

BACKGROUND: Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. METHODS: The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70-79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD). RESULTS: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H(2)O v 74.2 cm H(2)O, p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p<0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV(1)) was associated with IL-6 (adjusted regression coefficients (beta) = -5.3 (95% CI -9.1 to-1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to -1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8 (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. CONCLUSIONS: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV(1), quadriceps strength, and exercise capacity.

Airflow limitation is underrecognized in well-functioning older people.

OBJECTIVES: Dyspnea is a common symptom in older people. A reduced forced expiratory volume in 1 second (FEV1) is associated with a higher mortality rate from cardiovascular and respiratory disease, and increased admissions to hospitals. Underrecognized or undertreated airflow limitation may exacerbate the problem. The purpose of this study was to assess the prevalence and treatment of airflow limitation in a cohort of well-functioning older people. DESIGN: Cross-sectional study. SETTING: Baseline of a clinical-epidemiological study of incident functional limitation. PARTICIPANTS: Participants attended the baseline examination of the Health, Aging, and Body Composition study, a prospective cohort study of 3,075 well-functioning subjects age 70 to 79. MEASUREMENTS: Demographic and clinical data were collected by interview. Spirometry was performed unless contraindicated and repeated until three acceptable sets of flow-volume loops were obtained. Patients on bronchodilator medications had spirometry performed posttherapy. Blinded readers assessed the flow-volume loops, and inadequate tests were omitted from analysis. Airflow limitation was defined as a reduced forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) as determined by age-, sex-, and race-normalized values. Severity of airflow limitation was defined by American Thoracic Society criteria. RESULTS: Two thousand four hundred eighty-five subjects (80.8%) had assessable spirometry and data on treatment and diagnosis (1,265 men, 1,220 women). The mean age was 73.6 years. Two hundred sixty-two subjects (10.5%) had airflow limitation; 43 (16.4%) of these never smoked. Only 37.4% of participants with airflow limitation and 55.6% of participants with severe airflow limitation reported a diagnosis of lung disease. Only 20.5% of subjects with at least moderate airflow limitation had used a bronchodilator in the previous 2 weeks. CONCLUSION: Despite their good functional status, airflow limitation was present, and underrecognized, in a considerable proportion of our older population. The low bronchodilator use suggests a significant reservoir of untreated disease. Physicians caring for older people need to be more vigilant for both the presence, and the need for treatment, of airflow limitation.

Do sweat calcium losses affect bone mass during firefighter training?

Although participation in vigorous exercise is associated with increased bone mass, recent evidence suggests that loss of calcium in sweat may result in a negative calcium balance and, ultimately, a decrease in bone mass. Anthropometric characteristics, habitual physical activity levels, dietary calcium intake, bone mineral content, and bone turnover markers were measured in 42 male recruits before and after 4 months of firefighter training. During two strenuous mid-training sessions, sweat calcium concentrations were measured; they averaged 1.1 mM. Whole body and total hip bone mineral content increased significantly, as did one marker of bone formation, and were not associated with sweat calcium concentration. This study demonstrates that intense physical training sessions that produce high sweat rates do not have an adverse effect on the bone mineral content of healthy young men.

Accelerating Scientific Discovery Through Computation and Visualization.

The rate of scientific discovery can be accelerated through computation and visualization. This acceleration results from the synergy of expertise, computing tools, and hardware for enabling high-performance computation, information science, and visualization that is provided by a team of computation and visualization scientists collaborating in a peer-to-peer effort with the research scientists. In the context of this discussion, high performance refers to capabilities beyond the current state of the art in desktop computing. To be effective in this arena, a team comprising a critical mass of talent, parallel computing techniques, visualization algorithms, advanced visualization hardware, and a recurring investment is required to stay beyond the desktop capabilities. This article describes, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing and visualization to accelerate condensate modeling, (2) fluid flow in porous materials and in other complex geometries, (3) flows in suspensions, (4) x-ray absorption, (5) dielectric breakdown modeling, and (6) dendritic growth in alloys.

Clinical utility of lipid and lipoprotein levels during hospitalization for acute myocardial infarction.

The management of dyslipidemia after myocardial infarction (MI) is an important aspect of post-myocardial infarction care. However, acute changes in the lipid profile immediately following myocardial infarction have resulted in uncertainty regarding the clinical utility of lipid levels assessed during hospitalization for MI. We studied the effect of the timing of plasma lipid assessment among 294 patients who presented with MI to determine whether the differences between the serum lipid values in-hospital when compared with post-discharge values (generally 2-3 months after MI) would have a substantial impact on the decision to initiate lipid-lowering therapy. We found that the mean total and LDL cholesterol levels were significantly lower in-hospital when compared with generally 2-3 months later. However, patients whose lipids were measured within 48 h of presentation did not have significantly different values compared with generally 2-3 months post-discharge. Moreover, despite slightly lower in-hospital levels, 83.7% of patients were above the National Cholesterol Education Program target LDL for secondary prevention and 57.6% met the criteria for drug therapy based on in-hospital assessment. Total and LDL cholesterol levels fall modestly after an acute MI; however, from a clinical perspective, in-hospital levels can be used to guide decisions regarding lipid-lowering therapy which can begin in the immediate post-MI setting. In-hospital levels approximate post-MI levels, particularly if drawn within 48 h of presentation. All patients with acute myocardial infarction should have complete lipid profiles measured prior to discharge.

Misclassification and under-reporting of acute myocardial infarction by elderly persons: implications for community-based observational studies and clinical trials.

We investigated the accuracy of self-report of hospitalization for acute myocardial infarction (MI) by elderly persons in a community-based prospective study. Among 3809 persons aged 65 years or older followed up for 6 years, self-reported hospitalization for MI was validated by review of primary records and Medicare diagnoses. Among 147 who self-reported MI and for whom hospital records were available, the diagnosis was confirmed in 79 (54%). Myocardial infarction was not a reason for hospitalization among the remaining 68 participants; misclassification with other cardiovascular diagnoses was common. Medicare diagnosis correlated well with primary hospital records. Using Medicare diagnoses as the standard, the diagnosis of MI was confirmed in 53% of self-reports; the sensitivity and specificity of self-report were 51% and 98%, respectively. False-negative reporting was common because only half of hospitalizations for MI were reported. Self-report of hospitalization for MI by elderly persons in the community may be unreliable for ascertaining trends in cardiovascular diseases.

Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group.

Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults, aged 35-54 y, with diastolic blood pressure of 80-89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions (weight loss, sodium reduction, stress management, and supplementation with calcium, magnesium, potassium, and fish oil). At 6 and 18 mo, weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures (-2.9/-2.4 and -2.1/-1.2 mm Hg for weight loss and sodium reduction, respectively, at 18 mo). None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits. These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension. The long-term effects of both of these interventions are being tested in phase 2 of the trial.

Intraoperative salvage in patients undergoing elective abdominal aortic aneurysm repair: an analysis of cost and benefit.

PURPOSE: Although autologous blood procurement has become a standard of care in elective surgery, recent studies have questioned its cost-effectiveness. We therefore reviewed our 3-year experience with intraoperative cell salvage in patients who underwent elective abdominal aortic aneurysm repair. METHODS: A 3-year retrospective chart review of elective abdominal aortic aneurysm (infrarenal and suprarenal) repair was performed. Transthoracic repairs were excluded. RESULTS: Estimated blood lost was 1748 +/- 1236 ml, or 35% of baseline blood volume (5012 +/- 689 ml). Overall, 164 (89%) received red blood cell (RBC) transfusions (3.5 +/- 2.0 U/patient). The cost per patient for cell salvage was $315 +/- $97, representing 31% of all RBC costs and 24% of total blood component costs. Mean salvage volume infused was 578 +/- 600 ml; at a mean hematocrit level of 55.7% the RBC volume infused from salvage during surgery was 313 +/- 328 ml (representing 27% of total RBC volume lost during the hospital stay). This mean RBC volume salvaged represented the equivalent of 1.6 blood bank RBC units. The mean blood bank costs saved by using cell salvage was $248, or 79% of the $315 actually spent for salvage. We found no decrease in percentage of patients undergoing transfusion until salvage volumes that were infused exceeded 750 ml, or the equivalent of two blood bank units; all of these patients who benefitted had estimated blood lost > or = 1000 ml. CONCLUSIONS: We conclude that use of intraoperative cell salvage was most beneficial for patients who had estimated blood loss greater than or equal to 1000 ml and cell salvage volumes infused greater than or equal to 750 ml. Patients who are estimated to lose less than 1000 ml receive little benefit yet incur substantial costs from intraoperative cell salvage.

Recruitment for phase II of the Trials of Hypertension Prevention. Effective strategies and predictors of randomization. Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase II of the Trials of Hypertension Prevention is a multicenter, randomized, controlled trial designed to determine the efficacy of weight loss and reduction of sodium intake for lowering blood pressure and incidence of hypertension among persons with high-normal levels of blood pressure. The 2 x 2 factorial study design includes weight loss alone, restricted sodium intake alone, the combination of weight loss and sodium restriction, and a control group. Nine clinical centers used a variety of recruitment strategies to enroll 2382 participants over 17 months, which exceeded the sample size goal of 2250. Among randomized participants, 21% were minorities and 34% were women. Overall, direct mail generated the most randomized participants (73%), followed by community screening (12%) and media advertisement (11%). Referrals from community health care providers yielded few participants. Prescreening improved overall efficiency and reduced costs. Participants who were more likely to drop out voluntarily during the three-visit screening regimen tended to be younger, single, male, smokers, and less educated.

The effect of potassium supplementation in persons with a high-normal blood pressure. Results from phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

We conducted a randomized, double-blind, placebo-controlled trial of oral potassium chloride supplementation (60 mmol/d) in 353 men and women with an initial average diastolic blood pressure between 80 and 89 mm Hg. In the active (n = 178) compared to the placebo (n = 175) treatment group, the urinary potassium level was significantly (p < 0.001) increased by an average of 44.0 and 42.3 mmol/24 h following 3 and 6 months of therapy, respectively. Compared to placebo, active treatment was associated with a small (mean = 1.8 mm Hg) but significant (p = 0.04) reduction in diastolic blood pressure following 3 months of therapy. Following 6 months, however, this apparent treatment effect had virtually disappeared (mean reduction in diastolic blood pressure = 0.3 mm Hg). There was no significant effect of potassium supplementation on systolic blood pressure at either follow-up visit. There was a significant, independent, dose-response relationship between change in both 24-hour urinary potassium excretion and urinary sodium-potassium ratio and the corresponding change in diastolic blood pressure (-1.49 mm Hg for the highest versus the lowest quartile of change in urinary potassium excretion.