Browsing by Author "Pappas, Maria K."

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Delayed systolic blood pressure recovery following exercise as a mechanism of masked uncontrolled hypertension in chronic kidney disease
    (Oxford, 2017-10) Agarwal, Rajiv; Pappas, Maria K.; Medicine, School of Medicine
    Background Among people treated for hypertension, the presence of elevated blood pressure (BP) out of the clinic but normal BP in the clinic is called masked uncontrolled hypertension (MUCH). What causes MUCH remains unknown. The purpose of this study was to answer the question of whether patients with MUCH have an increased hemodynamic reactivity to exercise and delayed hemodynamic recovery following exercise. Methods Four groups were compared: controlled hypertension (CH, n = 58), MUCH (n = 34) and uncontrolled hypertension (UCH, n = 12), all of which had chronic kidney disease (CKD), and a group of healthy normal volunteers who did not have hypertension or CKD (n = 16). All participants underwent assessment of 24-h ambulatory BP monitoring, BP measurement during a graded symptom-limited exercise using a cycle ergometer and BP recovery over 7 min following exercise. Results Exercise-induced increase in systolic BP was similar among the four groups. When compared with healthy controls, recovery of systolic BP following termination of exercise was blunted among the CKD groups in unadjusted (P < 0.0001) and adjusted (P < 0.001) models. During recovery, the healthy control group had 5.9% decline in systolic BP per minute. In contrast, MUCH had only 3.3% per minute reduction and the UCH group had 0.3% reduction per minute. A test of linear trend was significant (P = 0.002, adjusted model). Conclusion Because there was no impairment in the heart rate recovery among groups, we speculate that the parasympathetic pathway appears intact among treated hypertensives with CKD. However, the failure to withdraw sympathetic tone upon termination of exercise causes ongoing vasoconstriction and delayed systolic BP recovery providing a biological basis for MUCH. Delayed recovery from exercise-induced hypertension in those with poorly controlled BP provides potentially a new target to assure round-the-clock BP control.
  • Thumbnail Image
    Item
    Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial
    (Oxford University Press, 2014-03-01) Agarwal, Rajiv; Sinha, Arjun D.; Pappas, Maria K.; Abraham, Terri N.; Tegegne, Getachew G.; Department of Medicine, IU School of Medicine
    Background The purpose of this study was to determine among maintenance hemodialysis patients with echocardiographic left ventricular hypertrophy and hypertension whether in comparison with a β-blocker-based antihypertensive therapy, an angiotensin converting enzyme-inhibitor-based antihypertensive therapy causes a greater regression of left ventricular hypertrophy. Methods Subjects were randomly assigned to either open-label lisinopril (n = 100) or atenolol (n = 100) each administered three times per week after dialysis. Monthly monitored home blood pressure (BP) was controlled to <140/90 mmHg with medications, dry weight adjustment and sodium restriction. The primary outcome was the change in left ventricular mass index (LVMI) from baseline to 12 months. Results At baseline, 44-h ambulatory BP was similar in the atenolol (151.5/87.1 mmHg) and lisinopril groups, and improved similarly over time in both groups. However, monthly measured home BP was consistently higher in the lisinopril group despite the need for both a greater number of antihypertensive agents and a greater reduction in dry weight. An independent data safety monitoring board recommended termination because of cardiovascular safety. Serious cardiovascular events in the atenolol group occurred in 16 subjects, who had 20 events, and in the lisinopril group in 28 subjects, who had 43 events {incidence rate ratio (IRR) 2.36 [95% confidence interval (95% CI) 1.36–4.23, P = 0.001]}. Combined serious adverse events of myocardial infarction, stroke and hospitalization for heart failure or cardiovascular death in the atenolol group occurred in 10 subjects, who had 11 events and in the lisinopril group in 17 subjects, who had 23 events (IRR 2.29, P = 0.021). Hospitalizations for heart failure were worse in the lisinopril group (IRR 3.13, P = 0.021). All-cause hospitalizations were higher in the lisinopril group [IRR 1.61 (95% CI 1.18–2.19, P = 0.002)]. LVMI improved with time; no difference between drugs was noted. Conclusions Among maintenance dialysis patients with hypertension and left ventricular hypertrophy, atenolol-based antihypertensive therapy may be superior to lisinopril-based therapy in preventing cardiovascular morbidity and all-cause hospitalizations. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number: NCT00582114)
  • Thumbnail Image
    Item
    Masked Uncontrolled Hypertension in CKD
    (American Society of Nephrology, 2016-03) Agarwal, Rajiv; Pappas, Maria K.; Sinha, Arjun D.; Department of Medicine, IU School of Medicine
    Masked uncontrolled hypertension (MUCH) is diagnosed in patients treated for hypertension who are normotensive in the clinic but hypertensive outside. In this study of 333 veterans with CKD, we prospectively evaluated the prevalence of MUCH as determined by ambulatory BP monitoring using three definitions of hypertension (daytime hypertension ≥135/85 mmHg; either nighttime hypertension ≥120/70 mmHg or daytime hypertension; and 24-hour hypertension ≥130/80 mmHg) or by home BP monitoring (hypertension ≥135/85 mmHg). The prevalence of MUCH was 26.7% by daytime ambulatory BP, 32.8% by 24-hour ambulatory BP, 56.1% by daytime or night-time ambulatory BP, and 50.8% by home BP. To assess the reproducibility of the diagnosis, we repeated these measurements after 4 weeks. Agreement in MUCH diagnosis by ambulatory BP was 75-78% (κ coefficient for agreement, 0.44-0.51), depending on the definition used. In contrast, home BP showed an agreement of only 63% and a κ coefficient of 0.25. Prevalence of MUCH increased with increasing clinic systolic BP: 2% in the 90-110 mmHg group, 17% in the 110-119 mmHg group, 34% in the 120-129 mmHg group, and 66% in the 130-139 mmHg group. Clinic BP was a good determinant of MUCH (receiver operating characteristic area under the curve 0.82; 95% confidence interval 0.76-0.87). In diagnosing MUCH, home BP was not different from clinic BP. In conclusion, among people with CKD, MUCH is common and reproducible, and should be suspected when clinic BP is in the prehypertensive range. Confirmation of MUCH diagnosis should rely on ambulatory BP monitoring.
  • Thumbnail Image
    Item
    A randomized trial of intravenous and oral iron in chronic kidney disease
    (Nature Publishing Group, 2015-10) Agarwal, Rajiv; Kusek, John W.; Pappas, Maria K.; Department of Medicine, IU School of Medicine
    Although iron is commonly used to correct iron deficiency anemia (IDA) in chronic kidney disease (CKD), its effect on kidney function is unclear. To assess this, we randomly assigned patients with stage 3 and 4 CKD and IDA to either open-label oral ferrous sulfate (69 patients to 325 mg three times daily for 8 weeks) or intravenous iron sucrose (67 patients to 200 mg every 2 weeks, total 1 g). The primary outcome was the between-group difference in slope of measured glomerular filtration rate (mGFR) change over two years. The trial was terminated early on the recommendation of an independent data and safety monitoring board based on little chance of finding differences in mGFR slopes, but a higher risk of serious adverse events in the intravenous iron treatment group. mGFR declined similarly over two years in both treatment groups (oral -3.6 ml/min per 1.73 m(2), intravenous -4.0 ml/min per 1.73 m(2), between-group difference -0.35 ml/min per 1.73 m(2); 95% confidence interval -2.9 to 2.3). There were 36 serious cardiovascular events among 19 participants assigned to the oral iron treatment group and 55 events among 17 participants of the intravenous iron group (adjusted incidence rate ratio 2.51 (1.56-4.04)). Infections resulting in hospitalizations had a significant adjusted incidence rate ratio of 2.12 (1.24-3.64). Thus, among non-dialyzed patients with CKD and IDA, intravenous iron therapy is associated with an increased risk of serious adverse events, including those from cardiovascular causes and infectious diseases.