Effect of Intensive Blood-Pressure Treatment on Patient-Reported Outcomes.

BACKGROUND: The previously published results of the Systolic Blood Pressure Intervention Trial showed that among participants with hypertension and an increased cardiovascular risk, but without diabetes, the rates of cardiovascular events were lower among those who were assigned to a target systolic blood pressure of less than 120 mm Hg (intensive treatment) than among those who were assigned to a target of less than 140 mm Hg (standard treatment). Whether such intensive treatment affected patient-reported outcomes was uncertain; those results from the trial are reported here. METHODS: We randomly assigned 9361 participants with hypertension to a systolic blood-pressure target of less than 120 mm Hg or a target of less than 140 mm Hg. Patient-reported outcome measures included the scores on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Veterans RAND 12-Item Health Survey, the Patient Health Questionnaire 9-item depression scale (PHQ-9), patient-reported satisfaction with their blood-pressure care and blood-pressure medications, and adherence to blood-pressure medications. We compared the scores in the intensive-treatment group with those in the standard-treatment group among all participants and among participants stratified according to physical and cognitive function. RESULTS: Participants who received intensive treatment received an average of one additional antihypertensive medication, and the systolic blood pressure was 14.8 mm Hg (95% confidence interval, 14.3 to 15.4) lower in the group that received intensive treatment than in the group that received standard treatment. Mean PCS, MCS, and PHQ-9 scores were relatively stable over a median of 3 years of follow-up, with no significant differences between the two treatment groups. No significant differences between the treatment groups were noted when participants were stratified according to baseline measures of physical or cognitive function. Satisfaction with blood-pressure care was high in both treatment groups, and we found no significant difference in adherence to blood-pressure medications. CONCLUSIONS: Patient-reported outcomes among participants who received intensive treatment, which targeted a systolic blood pressure of less than 120 mm Hg, were similar to those among participants who received standard treatment, including among participants with decreased physical or cognitive function. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062 .).

Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT.

BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.

Chronic Kidney Disease Classification in Systolic Blood Pressure Intervention Trial: Comparison Using Modification of Diet in Renal Disease and CKD-Epidemiology Collaboration Definitions.

BACKGROUND: Interventional trials have used either the Modification of Diet in Renal Disease (MDRD) or chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation for determination of estimated glomerular filtration rate (eGFR) to define whether participants have stages 3-5 CKD. The equation used to calculate eGFR may influence the number and characteristics of participants designated as having CKD. METHODS: We examined the classification of CKD at baseline using both equations in the Systolic Blood Pressure Intervention Trial (SPRINT). eGFR was calculated at baseline using fasting serum creatinine values from a central laboratory. RESULTS: Among 9,308 participants with baseline CKD classification using the 4-variable MDRD equation specified in the SPRINT protocol, 681 (7.3%) participants were reclassified to a less advanced CKD stage (higher eGFR) and 346 (3.7%) were reclassified to a more advanced CKD stage (lower eGFR) when the CKD-EPI equation was used to calculate eGFR. For eGFRs <90 ml/min/1.73 m2, participants <75 years were more likely to be reclassified to a less advanced CKD stage; this reclassification was more likely to occur in non-blacks rather than blacks. Participants aged ≥75 years were more likely to be reclassified to a more advanced than a less advanced CKD stage, regardless of baseline CKD stage. Reclassification of baseline CKD status (eGFR <60 ml/min/1.73 m2) occurred in 3% of participants. CONCLUSIONS: Use of the MDRD equation led to a higher percentage of participants being classified as having CKD stages 3-4. Younger and non-black participants were more likely to be reclassified as not having CKD using the CKD-EPI equation.

Blood pressure control by drug group in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Blood pressure (BP) control rates and number of antihypertensive medications were compared (average follow-up, 4.9 years) by randomized groups: chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40 mg/d (n=9054) in a randomized double-blind hypertension trial. Participants were hypertensives aged 55 or older with additional cardiovascular risk factor(s), recruited from 623 centers. Additional agents from other classes were added as needed to achieve BP control. BP was reduced from 145/83 mm Hg (27% control) to 134/76 mm Hg (chlorthalidone, 68% control), 135/75 mm Hg (amlodipine, 66% control), and 136/76 mm Hg (lisinopril, 61% control) by 5 years; the mean number of drugs prescribed was 1.9, 2.0, and 2.1, respectively. Only 28% (chlorthalidone), 24% (amlodipine), and 24% (lisinopril) were controlled on monotherapy. BP control was achieved in the majority of each randomized group-a greater proportion with chlorthalidone. Over time, providers and patients should expect multidrug therapy to achieve BP <140/90 mm Hg in a majority of patients.

Effects of nurse counseling on walking for exercise in elderly primary care patients.

Background. Counseling sedentary primary care patients can increase physical activity, but whether this approach will increase exercise and fitness in elderly adults with chronic diseases remains to be determined. Methods. After receiving individualized nurse counseling to begin a program of walking for health, 60- to 80-year-old primary care patients were randomized to one of three levels of telephone contacts over 10 months: (i) 20 nurse-initiated calls, (ii) 10 nurse-initiated calls plus 10 motivational calls programmed through an automated phone calling system, or (iii) no program-initiated phone contacts. Self-reported (diary) walking adherence was the primary outcome; other activity, social support, health quality of life, and measured walking performance, mobility, and body mass index and girths were also assessed during the initiation (months 1-6) and maintenance (months 7-10) phases of the trial. Results. Average adherence for the 181 participants to the goal of walking at least 20 minutes on 3 or more days per week was 44% for initiation and 42% for maintenance. Participants receiving the combination of nurse-initiated personal and automated phone calls walked significantly more frequently than those with no phone contacts. Fitness improved in all three groups; changes were generally correlated with self-reported walking. Having a companion was associated with more frequent walking. Perceived quality of physical and mental health did not change. Conclusions. Simple and relatively inexpensive nurse contacts can motivate elderly primary care patients to walk for exercise, and this activity is associated with measurable health benefits.

Evaluation of the 7-day physical activity recall in urban and rural men.

PURPOSE: To assess reliability and validity of the 7-d physical activity recall (PAR) in 60- to 80-yr-old men from urban and rural homes in the southeastern United States. METHODS: Two hundred twenty 60- to 80-yr-old men (29% minority ethnicity) from Veterans Affairs primary care clinics completed two PAR interviews at 2- to 4-wk intervals. The PAR included modifications to elicit and score light-moderate (2-3 METs) as well as moderate (3-6 METs) and hard (>/=7 METs) physical activity. Reliability was assessed using intraclass correlations from the two interviews. Validity was assessed using Spearman correlations of PAR variables with 6-min walk performance, and with treadmill performance and accelerometer activity counts from subsamples, as well as measures of gait, balance, activities of daily living, and perceived quality of life. Results were examined separately for urban and rural participants. RESULTS: Reliability coefficients were acceptable and PAR measures of estimated energy expenditure, and time spent in hard, moderate, and light-moderate activity correlated as hypothesized with the fitness and health measures. CONCLUSION: Reliability and validity coefficients were generally similar to those found in studies of the PAR with younger samples and with instruments designed specifically for use with elders. The PAR is a useful and flexible instrument for assessing physical activity of varying intensity in older men living in both urban and rural home settings.

Gender differences and similarities in effects of nonpharmacologic approaches to the treatment of mild hypertension.

TAIM, the Trial of Antihypertensive Interventions and Management, studied the effects of dietary sodium restriction or weight reduction, alone and in combination with low-dose diuretic or beta blocker on blood pressure after 6 months. The responses to these interventions of men compared to women are presented for those persons randomized to placebo drug. Men undergoing a weight-reduction intervention were able to lose more weight (5.9 kg) than women (3.1 kg), P ⩽ 05. Men also had a greater percentage of wright loss and a greater reduction in body mass index (BMI), although not significantly so. Weight loss was correlated to a decrease in triglycerides (r = 0.37), but not in cholesterol. The weight-reduction intervention lowered triglycerides more in men (-81 mg/dl) than in women(-21 mg/dl; P = .008). There were no sex differences in abiility to reduce sodium or increase potassium for those in the sodium restriction group. Both men and women decreased their sodium to the same extent by 36 mmol/day and 25 mmol, respectively, and increased their potassium by 13 mmol and 11 mmol, respectively. Blood pressure response at 6 months was greater in men than in women on weight reduction (a drop in diastolic pressure of -11 mmHg in men and 7 mmHg in women, P =.04). Sodium restriction had a similar effect on blood pressure in both sexes, and among men resulted in a significantly smaller reduction in blood pressure than did weight reduction. © 1995 Wiley-Liss, Inc.

Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants.

OBJECTIVE: To assess the reversibility of the elevation of serum creatinine levels in patients with diabetes after 5 years of continuous on-trial fenofibrate therapy. RESEARCH DESIGN AND METHODS: An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate posttrial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, ≥ 20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, ≤ 2% increase); and placebo control subjects (n = 565). Serum creatinine and cystatin C were measured at trial end and 6-8 weeks after discontinuation of trial therapy. RESULTS At trial end, case subjects had the highest adjusted serum creatinine (± SE) mg/dL (1.11 ± 0.02) and the lowest adjusted estimated glomerular filtration rate (eGFR) (± SE) mL/min/1.73 m(2) (68.4 ± 1.0) versus control subjects (1.01 ± 0.02; 74.8 ± 1.3) and placebo subjects (0.98 ± 0.01; 77.8 ± 0.7). After 51 days off-drug, serum creatinine in case subjects was still higher (0.97 ± 0.02) and eGFR still lower (77.8 ± 1.0) than control subjects (0.90 ± 0.02; 81.8 ± 1.3) but not different from placebo subjects (0.99 ± 0.01; 76.6 ± 0.7). Changes in serum cystatin C recapitulated the serum creatinine changes. CONCLUSIONS: Participants with significant initial on-trial increases in serum creatinine (≥ 20%) returned to the same level of renal function as participants receiving placebo while participants who had ≤ 2% increase in serum creatinine had net preservation of renal function compared with the same unselected placebo reference group. The fenofibrate-associated on-trial increases in serum creatinine were reversible, and the reversal was complete after 51 days off-drug. The similarity of the cystatin C results suggests that the mechanism of this change is not specific for serum creatinine.

Counseling for home-based walking and strength exercise in older primary care patients.

BACKGROUND: We evaluated the effects of counseling linked with primary care visits on walking and "strength exercise" (the combination of strength-building and flexibility exercise) in aging veterans. METHODS: Male veterans aged 60 to 85 years (N = 224) with physical function limitations were randomized to either counseling for home-based walking and strength exercise (EXC) or discussion of their choice of health education topics (EDUC) with a nurse at baseline, 1 month, and 5 months. The EXC participants recorded exercise on monthly calendars and received brief follow-up calls from the nurse; all participants received bimonthly newsletters throughout the 10-month trial. RESULTS: Retention was 83% in the EXC group and 97% in the EDUC group (P < .001). With analyses using the last observation carried forward approach, the EXC participants reported more walking time per week at 5 and 10 months (64.5 and 60.6 min/wk, respectively, for the EXC group vs 50.5 and 45.7 min/wk, respectively, for the EDUC group; 2.4 d/wk and 2.3 d/wk, respectively, for the EXC group vs 1.8 and 1.7 d/wk, respectively, for the EDUC group) (P < .001). The EXC participants also reported more strength exercise at 5 and 10 months (44.6 and 41.2 min/wk, respectively, for the EXC group vs 19.8 and 14.7 min/wk, respectively, for the EDUC group; 2.1 and 2.0 d/wk, respectively, for the EXC group vs 0.8 and 0.8 d/wk, respectively, for the EDUC group) (P < .001). The EXC participants reported more frequent moderate- or higher-intensity physical activity (7.1 vs 5.1 sessions/wk) (P < .001). Findings from accelerometer-measured physical activity indicated more EXC than EDUC participants (64% vs 46%), who averaged 30 min/d or more of moderate- or higher-intensity physical activity (P = .03). Participants engaging in strength exercise improved physical performance and reported positive changes in quality of life. CONCLUSION: Relatively brief counseling linked with primary care visits can increase home-based walking and strength exercise in aging male veterans. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00013195.

Efficacy of a program to encourage walking in VA elderly primary care patients: the role of pain.

Pain may be a barrier or a negative outcome of initiating and maintaining an exercise program in elderly patients. The purpose of this study was to examine the role of pain in a program designed to increase walking for exercise in 181 veteran primary care patients (60 - 80 years). Self-reported physical activity (min-walked per week) and pain were assessed at baseline, 6, and 12 months. Walking for exercise increased over time without significant changes in pain. Analyses suggested that baseline pain was not a barrier to initiating or maintaining a walking exercise program, nor did increased walking influence reports of pain. These results suggest that patients can be encouraged to engage in physical activity, even if they are currently suffering from pain.

Physical activity in patients who are severely mentally ill: feasibility of assessment for clinical and research applications.

Few studies have examined physical activity in patients who are severely mentally ill. We assessed feasibility and validity of using standardized self-report and objective measures of physical activity in 20 community-dwelling veteran patients, most with psychotic disorders and substance abuse in remission. Test-retest reliability of a past week physical activity survey and the Community Healthy Activities Model Program for Seniors interview were evaluated with repeated interviews. RT3 accelerometer data provided objective physical activity data. Test-retest reliability and validity correlations for the self-report instruments were similar in magnitude to those reported for nonclinical adult samples. Some activity measures were correlated with cognitive status and quality of life. Results indicate that self-reported physical activity can provide valid information for clinical and research applications in mental health settings. Correlations between physical activity measures and psychiatric symptoms suggested interesting patterns for future study.