Effects of the circadian time of antihypertensive treatment on the ambulatory blood pressure pattern of elderly patients with essential hypertension

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Untreated subjects Variable

1st session

2nd session

% of nearTest-retest Bland-Altman maximal correlation coefficient variability

Clinic SBP/DBP 146 ⫾ 16/87 ⫾ 12 143 ⫾ 21/86 ⫾ 11 0.58/0.57 Awake SBP/DBP 140 ⫾ 15/86 ⫾ 19 139 ⫾ 11/83 ⫾ 9 0.54/0.33 Clinic-awake 6 ⫾ 18/0 ⫾ 20 5 ⫾ 11/3 ⫾ 11 0.69/0.28 SBP/DBP difference

36/22 26/37 32/40

54/52 56/78 44/78

Similar results were obtained for the total population. Thus, the relation between a subject’s clinic SBP and awake SBP, even in our practicebased setting, is a repeatable ABPM variable both categorically and as a continuous variable. Key Words: Masked Hypertension, Reproducibility, White Coat Hypertension

P-49 24-HOUR AVERAGE HEART RATE IN PATIENTS WITH INSULIN RESISTANCE Enrique Bernal, Olivia Sanchez, Eva Fernandez, Begonia Monge, Judith Marquez, Rosa Fabregate, Angela Trueba, Jose Saban-Ruiz. Endothelial Pathology Unit, Ramon y Cajal Hospital, Madrid, Madrid, Spain. Introduction: Studies have demostrated an increase in cardiovascular risk related with heart rate(HR)⬎80 bpm. An association between HR and other risk factors has been found, including the components of the metabolic syndrome(MS), and both could be reflective of an activation of the sympathetic nervous system(SNS). Objectives: 1.To correlate mean HR with Insulin resistance(IR), and MS. 2.To verify if the increase in HR correlates in an independent way with C-reactive protein(CRP)as an inflammatory marker. Methods: N⫽190;98M,aged 35-85(58⫹-12),110 hypertensives,93 DM2, 65 dyslipemics,28 smokers.BMI(Kg/m2), waist(cm), Glycaemia, Triglycerides, Chol, HDLc HITACHI, LDL:Friedewald, Insulinaemia (␮U/mL) Inmmulite DPC, C-peptide(ng/mL) Inmulite 2000 and IR(HOMA score).CRP(mg/l):Nephelometer. Hemodynamic parameters: ABPM:Spacelabs Model 90207.Average Systolic,Diastolic and Mean BP, Ambulatory Pulse Pressure(PP),HR. Statistical analysis: t-Student, Chi-square,multivariate analysis. Results: 1.A total of 44.2% of patients had a Mean HR⬎75 bpm.They were younger(p⫽0.008) and had a greater waist circumference(p⫽0.001), IR(p⫽0.007), insulinaemia(p⫽0,016), C-peptide (p⫽0.001) and triglyceridemia(p⫽0,004). There were no differences in relation to BMI, glycaemia, chol, LDL and HDL. 2.Patients with a higher average HR had greater average Systolic BP(p⫽0,023), Diastolic BP(p⬍0,001), Mean BP(p⬍0,001) and PP(p⫽0,012). 3.CRP was higher in patients with elevated HR(p⬍0,05). Conclusions: 1.Average HR⬎75 bpm is correlated with waist circumference, IR, insulinaemia, C-peptide and triglyceridemia. 2.In spite of being of younger, patients with a higher average HR had greater Systolic BP, Diastolic BP, Mean BP and PP. 3.CRP was higher in patients with greater HR,but not in an independent way. 4.Activated SNS could participate in the genesis of the MS and its complications. 5.Average HR could be a reliable marker of this activation and its consequences. Key Words: Ambulatory Blood Pressure Monitoring, Heart Rate, Insulin Resistance

P-50 HOME BLOOD PRESSURE MONITORING: A SUITABLE EVALUATION TOOL FOR PROBE DESIGNED TRIALS. COSIMA STUDY Guillaume Bobrie, Alain Giacomino, Nicolas Postel-Vinay, Cyril Moulin, Roland Asmar. Hypertension, HEGP-Broussais, Paris, France; MG Recherches, Paris, France; Cardiology, Cardiovascular Institute, Paris, France. The purpose of the study was to demonstrate that home blood pressure monitoring (HBPM) with data teletransmission can be used in PROBE

AJH–May 2005–VOL. 18, NO. 5, PART 2

(prospective, randomised, open-label, blinded-endpoint) designed trials comparing the efficacy of 2 antihypertensives. Untreated or uncontrolled treated hypertensive adults (n⫽800) were enrolled (V1) in a 5-week open-label lead-in phase in which they received 12.5 mg HCTZ od. Those whose blood pressure remained uncontrolled (office SBP ⬎ 140 mm Hg after 4 weeks (V2) and SBP measured by HBPM ⬎ 135 mm Hg at week 5 - at least 12 valid measurements over 5 days) were randomised (n⫽464) at V3 to either irbesartan/HCTZ (150/12.5 mg) or valsartan/HCTZ (80/12.5 mg) for 8 weeks. Treatment was administered every morning, except at the final visit (V4). BP measurements: after 5 minutes rest, 3 measurements were performed at 1 minute intervals in a sitting position. Office BP: sphygmomanometer or validated electronic device, same device and same arm throughout the study. HBPM: in the morning, before treatment intake (6-10 am) and in the evening (6-10 pm), for at least 3 days; validated device, Tensioday®, with data teletransmission at weeks 5 (before V3) and 13 (before V4) to an independent core laboratory blinded to treatment allocation. The intent-to-treat dataset included 449 patients (irbesartan/HCTZ: 222 and valsartan/HCTZ: 227). Baseline characteristics were well matched: mean age 59.3, 56% men; initial home SBP/DBP 148.8/89.5 mm Hg and office SBP/DBP 153.0/90.6 mm Hg. The differences (mm Hg) in HBPM (W5-W13) and office BP (V3-V4) are presented in the table below. mm Hg

⌬ Home SBP

⌬ Home DBP

⌬ office SBP

⌬ office DBP

irbesartan/HCTZ valsartan/HCTZ ⌬, mean [95CI] p

13.0 ⫾ 9.5 10.6 ⫾ 9.5 2.4 [0.6;4.2] 0.0094

9.5 ⫾ 6.2 7.4 ⫾ 6.2 2.0 [0.9;3.2] 0.0007

15.0 ⫾ 11.2 11.8 ⫾ 11.2 3.2 [1.1;5.3] 0.0027

8.6 ⫾ 7.1 6.9 ⫾ 7.1 1.7 [0.4;3.0] 0.0113

All values are expressed as mean ⫾ sd / CI: confidence interval

The overall safety was similar in the two groups. In conclusion, the superiority of the combination irbesartan/HCTZ over valsartan/HCTZ evidenced in an objective manner, independently from the investigator by HBPM with data teletransmission, supports the usefulness of such a technique in PROBE designed trials. Key Words: Home Blood Pressure Monitoring, Irbesartan/HCTZ, Valsartan/HCTZ

P-51 EFFECTS OF THE CIRCADIAN TIME OF ANTIHYPERTENSIVE TREATMENT ON THE AMBULATORY BLOOD PRESSURE PATTERN OF ELDERLY PATIENTS WITH ESSENTIAL HYPERTENSION Carlos Calvo, Ramon C Hermida, Diana E Ayala, Jose E Lopez, Marta Rodriguez, Manuel Covelo. Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago, Spain; Bioengineering and Chronobiology Labs, University of Vigo, Vigo, Spain. Recent results indicate that non-dipping in hypertensive patients treated with single morning doses is markedly related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097-1104]. In the elderly, as compared to younger patients, the day/night ratio of blood pressure (BP) (calculated as the nocturnal decline of BP relative to the diurnal mean) is diminished due to a progressive increase in nocturnal BP with aging. Accordingly, we studied the impact of antihypertensive treatment and the time of therapy on the circadian pattern of BP in elderly patients with essential hypertension. We studied 1286 elderly patients with grade 1-2 essential hypertension (573 men), 68.4⫾5.6 years of age. Among them, 352 patients were untreated at the time of the study, 547 patients were receiving all their antihypertensive medication upon awakening, and 387 were taken one antihypertensive drug at bedtime. BP was measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately

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calculate the diurnal and nocturnal means of BP on a per subject basis. Among untreated patients, 62.5% were non-dippers. In treated patients, BP was highly reduced during diurnally active hours, but not during nocturnal sleep, as compared to untreated patients. The percentage of non-dippers among treated patients was increased up to 66.3%. As a function of the circadian time of treatment, 75.2% of the patients with all drugs on awakening were non-dippers. This percentage was significantly reduced to just 53.7% in patients who received one antihypertensive drug at bedtime (P⬍0.001). Antihypertensive therapy, mostly given exclusively upon awakening, significantly modifies the circadian pattern of BP. In the elderly, pharmacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient, as a function of the therapeutic coverage of the drugs and the baseline circadian BP profile of the patient. This chronotherapeutic approach allows reducing the prevalence of an altered non-dipper BP profile, associated with an increased cardiovascular risk.

These results may improve the way pulsatile and steady hemodynamics are quantified in central arteries.

Key Words: Chronotherapy, Elderly Patients, Non-Dipper

P-52 FRACTIONAL SYSTOLIC PRESSURE AND FRACTIONAL DIASTOLIC PRESSURE ARE RECIPROCAL INDICES OF PULSATILITY IN THE AORTA Denis Chemla, Isabelle Antony, Karen Zamani, Alain Nitenberg. Physiology, CHU de Biceˆtre-Universite Paris-Sud 11, 94275 Le Kremlin-Bicetre, France; Physiology, CHU Jean Verdier - Universite´ Paris 13, 93143 Bondy, France. Background: In the ascending aorta, the fractional systolic pressure (FSP), i.e., the systolic over mean pressure ratio (SAP/MAP), and the fractional diastolic pressure (FDP), i.e., the diastolic over mean pressure ratio (DAP/MAP), are related to the risk of coronary heart disease. Aortic pressure exhibit a sine-wave like pattern, such that the SAP/MAP and MAP/DAP ratios may display roughly similar values. Our study tested the hypothesis that FSP and 1/FDP gave interchangeable estimates of aortic pulsatility. Methods: We retrospectively analyzed high-fidelity pressures recorded at the aortic root level in 139 resting subjects (109 M / 30 F, 49 ⫹/- 12 years) including controls (C), hypertensives (HT), grafted heart (GH), idiopathic dilated cardiomyoapthy (IDCM) and miscellaneous cardiac diseases. Results: Data were obtained over a 66 to 160 mmHg MAP range (time-averaged). The FSP and 1/FDP values were similar in the overall population (1.35⫹/-0.12 vs 1.34⫹/-0.12) as well as in each subgroup (see Table).

Key Words: Fractional Diastolic Pressure, Fractional Systolic Pressure, Mean Aortic Pressure

P-53 CHARACTERISTICS OF NOCTURNAL DIPPING AND NONDIPPING 24-HOUR AMBULATORY BLOOD PRESSURE PATTERN AND ITS ASSOCIATED MORTALITY RISK AT A TERTIARY HYPERTENSION CENTER Kenneth L Choi, Paras Bhatt, William J Elliott. Preventive Medicine, Rush University Medical Center, Chicago, IL. Several prospective studies have shown that a nocturnal nondipping 24 hour ambulatory blood pressure pattern is associated with increased risk for mortality and cardiovascular events. We analyzed 553 patients who had a 24 hour ambulatory blood pressure monitor (ABPM) performed at our hypertension center from 1990 through 2004, and obtained mortality information from the Social Security Death Index through 01 November 2004. A normal nocturnal dipping pattern was defined by a greater than 10% decrease in average nocturnal systolic blood pressure (BP) compared to average daytime systolic BP. All patients who did not meet this criteria were classified as having a nocturnal nondipping pattern. The 332 (60.0%) patients with a nocturnal nondipping pattern were more likely to be female (52.7 vs 43.4%; P ⫽ 0.0003), had a higher average BP (136.3⫾15.2/81.8⫾10.5 vs 130.9⫾13.4/79.4⫾8.5 mm Hg, mean⫾ standard deviation; P ⬍ 0.001/0.003) and tended to be older (57.2 vs 54.9 years; P ⫽ 0.077) compared to the 221 (40.0%) patients with a normal nocturnal dipping pattern. The average nighttime systolic and diastolic BPs were higher in patients with a nondipping pattern compared to patients with a dipping pattern (134.3⫾16.1/78.9⫾11.1 vs 115.4⫾13.7/ 68.5⫾7.9 mmHg; p⬍0.001). During an average of 6.8⫾4.1 years of possible follow-up, 29 of the 332 (8.7%) patients with a nocturnal nondipping pattern died compared to 9 of the 221 (4.1%) patients with a nocturnal dipping pattern (unadjusted risk ratio⫽2.14; p⫽0.04 by logrank test). In a Cox proportional hazards model using 2 or 3 covariates, age was the major predictor of mortality (adjusted relative risk 1.09 per year, 95% confidence interval (CI): 1.06-1.12) and neither gender nor nondipping pattern was significant. The adjusted relative risk for nocturnal nondipping pattern was 1.69 (95% CI: 0.78-3.63). These data suggest that, in patients undergoing 24-hour ABPM at our hypertension center, a nocturnal nondipping BP pattern was associated with older age and female sex, with a trend toward increased mortality (after adjustment for baseline differences between patients with a nocturnal dipping and nondipping pattern). Key Words: Ambulatory Blood Pressure Monitor, Mortality, Nocturnal Nondipping Blood Pressure

Fractional systolic (ESP) and 1/fractional diastolic (FDP) pressure C, n ⫽ 31 HT, n ⫽ 46 GH, n ⫽ 18 IDCM, n ⫽ 14 Miscellaneous, n ⫽ 30

FSP

1/FDP

1.35 (0.10) 1.44 (0.11)* 1.26 (0.06)* 1.25 (0.08)* 1.29 (0.10)†

1.35 (0.10) 1.42 (0.13)* 1.25 (0.05)* 1.25 (0.06)* 1.30 (0.07)†

Values are means (SD). * P less than 0.01 vs C. † P ⫽ 0.05 vs C

As we found that (SAP/MAP ⫽ MAP /DAP), this implied that MAP was the square root of the SAP x DAP product, i.e., the geometric average of SAP and DAP (mean bias⫾SD ⫽ 0.3⫹/-2.7 mmHg; n⫽139). Other mathematical averages of SAP and DAP (arithmetic, harmonic and quadratic averages) as well as the classic empirical formulas were less reliable estimates of MAP. Conclusions: In the ascending aorta of resting humans, FSP and FDP were reciprocal estimates of pulsatility, thus implying that MAP was equal to the square root of the (SAP x DAP) product (“geometric MAP”).

P-54 CHARACTERISTICS OF WHITE COAT HYPERTENSION AND ITS ASSOCIATED MORTALITY RISK AT A TERTIARY HYPERTENSION CENTER Kenneth L Choi, Paras Bhatt, William J Elliott. Preventive Medicine, Rush University Medical Center, Chicago, IL. Several prospective studies have shown that white coat (WC) hypertension is associated with a lower risk of death and/or cardiovascular morbidity and mortality than sustained hypertension. We analyzed 554 patients who had a 24 hour ambulatory blood pressure monitor (ABPM) performed at our hypertension center from 1990 to 2004, and obtained mortality information from the Social Security Death Index through 01 November 2004. WC hypertension was diagnosed when the average office systolic BPs (measured by 3 or more readings at the beginning of the monitoring period) was ⱖ 10% higher than the daytime average