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. J Clin Hypertens (Greenwich). 2008;10:751-760.ª 2008 Le Jacq M ore than 70 million Americans-nearly 1 in 3 adults-have hypertension; its prevalence increases with age.

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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 anti-hypertensive 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.)

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.

OBJECTIVETo 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 METHODSAn 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.RESULTSAt 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 m2 (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.CONCLUSIONSParticipants 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.

A defect in urine concentrating ability occurs in individuals with sickle cell trait (HbAS). This may result from intracellular polymerization of sickle hemoglobin (HbS) in erythrocytes, leading to microvascular occlusion, in the vasa recta of the renal medulla. To test the hypothesis that the severity ofthe concentrating defect is related to the percentage of sickle hemoglobin present in erythrocytes, urinary concentrating ability was examined after overnight water deprivation, and intranasal desmopressin acetate (dDAVP) in 27 individuals with HbAS. The HbAS individuals were separated into those who had a normal a-globin genotype (aa/aa), and those who were either heterozygous (-a/aa) or homozygous (-a/-a) for gene-deletion a-thalassemia, because a-thalassemia modulates the HbS concentration in HbAS. The urinary concentrating ability was less in the aa/aa genotype than in the -a/aa or -a/-a genotypes (P < 0.05). After dDAVP, the urine osmolality was greater in patients with the -a/-a genotype than with the -a/aa genotype (882±37 vs. 672±38 mOsm/kg H20) (P < 0.05); patients with the -a/aa genotype had greater concentrating ability than individuals with a normal a-globin gene arrangement. There was an inverse linear correlation between urinary osmolality after dDAVP and the percentage HbS in all patients studied (r = -0.654; P < 0.05). A linear correlation also existed for urine concentrating ability and the calculated polymerization tendencies for an oxygen saturation of 0.4 and 0 (r = -0.62 and 0.69, respectively). We conclude that the severity of hyposthenuria in HbAS is heterogeneous. It is determined by the amount of HbS polymer, that in turn is dependent upon the percentage HbS, which is itself related to the a-globin genotype. (J. Clin.

Fractional lithium clearance (CLi/CIn), transit time occlusion time (e-TT/OT), and late proximal tubule fluid-to-plasma inulin ratio [1/(TF/P)In] determined by micropuncture were measured in the same kidney during 5-sec-butyl-5-ethyl-2-thiobarbituric acid (Inactin) anesthesia in rats fed either less than 2 mu eq sodium/g diet, rodent chow containing 20 mu eq sodium/g diet, or rodent chow and 0.5% NaCl to drink. Both CLi/CIn vs. e-TT/OT (r = 0.59) or 1(TF/P)In (r = 0.65) were linearly correlated at all sodium intakes. Quantitative estimates of proximal delivery by 1/(TF/P)In and e-TT/OT were similar (P = NS), whereas estimates from CLi/CIn were lower (P less than 0.05 or less) than the direct methods even when corrected for pars recta reabsorption. After acetazolamide or amiloride, but not furosemide, all methods for proximal delivery correlated quantitatively (P = NS) in sodium-restricted rats. Between amiloride and nondiuretic sodium-restricted rats, 1/(TF/P)In was not different. Proximal delivery estimated by CLi/CIn slightly (P = NS) underestimated direct measurements during 2% volume expansion [fractional sodium excretion (FeNa) 0.65 +/- 0.08%]. Thus, in the rat, CLi/CIn is not a quantitative estimate of proximal delivery if FeNa is less than 0.65% due to distal lithium reabsorption. CLi/CIn determined after amiloride may provide a correct estimate of proximal delivery during sodium restriction.

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