G. Bilo

Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditionsA joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine

Abstract Take home figure Adapted from Bärtsch and Gibbs2 Physiological response to hypoxia. Life-sustaining oxygen delivery, in spite of a reduction in the partial pressure of inhaled oxygen between 25% and 60% (respectively at 2500u2009m and 8000u2009m), is ensured by an increase in pulmonary ventilation, an increase in cardiac output by increasing heart rate, changes in vascular tone, as well as an increase in haemoglobin concentration. BP, blood pressure; HR, heart rate; PaCO2, partial pressure of arterial carbon dioxide.

Blood pressure response to six-minute walk test in hypertensive subjects exposed to high altitude: effects of antihypertensive combination treatment

ABSTRACT Background Limited evidence exists on blood pressure (BP) responses to exercise in hypertensive subjects exposed to high altitude, and on the effects of antihypertensive treatment in this setting. We aimed to asses BP response to submaximal exercise in hypertensive lowlanders acutely exposed to high altitude, and the effects of a calcium antagonist–angiotensin receptor blocker combination in this condition. Methods 89 mild-hypertensive participants in HIGHCARE-ANDES study performed a six-minute walk test in 3 conditions: at sea-level off-treatment; at sea-level after 6weeks of double-blind treatment with telmisartan 80mg+slow release nifedipine 30mg or with placebo; on the first full day of permanence at 3260m altitude under randomized treatment. Results The distance walked in 6min was reduced by about 10% at high altitude in both groups (p Conclusions In mild hypertensives, acute exposure to high altitude enhances the BP response to exercise. Such an enhanced response is effectively reduced by telmisartan/nifedipine combination therapy, without affecting exercise performance.

Blood pressure variability: clinical relevance and application

Blood pressure variability is an entity that characterizes the continuous and dynamic fluctuations that occur in blood pressure levels throughout a lifetime. This phenomenon has a complex and yet not fully understood physiological background and can be evaluated over time spans ranging from seconds to years. The present paper provides a short overview of methodological aspects, clinical relevance, and potential therapeutic interventions related to the management of blood pressure variability.

BLOOD PRESSURE VARIABILITY AS A PREDICTOR OF CARDIOVASCULAR MORTALITY: RESULTS OF DUBLIN OUTCOME STUDY: 4B.01

Objective: While the relationship of blood pressure (BP) variability (V) with organ damage is fairly well documented, the data on its relationship with cardiovascular (CV) events and mortality is controversial. The aim of this study was to evaluate the relationship of BPV estimated with different methods with cardiovascular mortality in a large cohort of previously untreated subjects. Methods: The study included 10,538 subjects (age 54.4 ± 14.5, 47% males) referred for assessment of their hypertension between 1982 and 2002 in Dublin, Ireland, in whom 24 hour ambulatory blood pressure monitoring of adequate quality was obtained off treatment. BPV was assessed separately for systolic (S) and diastolic (D) BP as 24 h standard deviation (SD), weighted 24 h standard deviation (wSD), daytime SD and night-time SD. The association of these variables with cardiovascular mortality ascertained through the analysis of death certificates was assessed in Cox regression models adjusted for age, sex, BMI, smoking status, diabetes, previous cardiovascular disease, 24 h SBP and 24 h DBP. Results: 498 CV deaths occurred in the study population over the average follow-up period of 5.8 years. 24 h SBP SD showed a weak inverse relationship with CV mortality (ß = −0.024, p = 0.03), which disappeared when nocturnal BP fall was included in the model. No other estimate of SBP variability was related to the outcome. DBP wSD and daytime SD were directly and significantly related to CV mortality (ß = 0.053, p = 0.003 and ß = 0.040, p = 0.006, respectively) while the relation of the outcome with 24 h DBP SD (p = 0.55) and night-time DBP SD (p = 0.11) was not significant. Figure shows the Kaplan-Meier survival curves for subjects stratified according to DBP wSD below or above 10 mmHg. Figure 1. No caption available. Conclusions: The relationship of 24 h BP SD with CV mortality is affected by the contribution of nocturnal fall to 24 h BPV. When BPV is assessed with other methods, devoid of interference from nocturnal BP fall, variability of DBP (but not of SBP) appears to independently predict CV mortality. Both wSD and daytime SD appear superior to night-time SD in this regard.

CENTRAL SLEEP APNEAS AND BLOOD PRESSURE DURING ACUTE EXPOSURE TO MODERATE ALTITUDE

Objective: The association between obstructive sleep apnea (OSA) and both acute and chronic blood pressure (BP) increase is well established but it is not clear whether similar relationship exists for central sleep apneas (CSA). CSA are common in advanced heart failure but in these patients BP is usually low due to the effects of the disease and drugs used. Exposure to elevated altitudes may induce both CSA and BP increase. Aim of this study was to investigate the relationship between the presence of CSA and BP changes in healthy subjects acutely exposed to moderate altitude (MA). Design and method: 44 healthy volunteers (mean age 41u200a±u200a12y, 16 males) residing at low altitude were transported to the altitude of 2035 m asl (Sestriere, Italy). During the first and second 24-hours of exposure they underwent in a random order 24-hour ambulatory BP monitoring (AND TM-2430) and cardiorespiratory sleep study (Embletta). The investigations were performed also at sea level (SL). Analyses involved pairwise comparisons of BP and cardiorespiratory variables between SL and MA as well as unadjusted and adjusted correlations between changes in these variables. Results: Significant increases occurred at MA in 24-hour, daytime and night-time systolic/diastolic BP (difference vs. SL 5.36u200a±u200a8.4/3.55u200a±u200a4.6, 4.98u200a±u200a11.0/2.98u200a±u200a6.7, 4.97u200a±u200a10.8/3.75u200a±u200a7.0 mmHg), respectively. No changes in the size of nocturnal BP fall were observed. In parallel, the rate of CSA increased (total Apnea Hypopnea Index: 1.55 vs 4.90, pu200a<u200a.0001; central apnea index: 0.75 vs 1.30, pu200a=u200a0.0004; Oxygen Desaturation Index 1.50 vs 7.85, pu200a<u200a.0001 for SL vs MA, respectively), while mean nocturnal oxyhemoglobin saturation decreased (95.7u200a±u200a1.5% vs. 91.6u200a±u200a1.5%, pu200a<u200a.001). No correlations between BP changes and indices characterizing breathing during sleep were observed either in univariate analysis (all correlation coefficientsu200a<u200a0.2) or after considering possible confounders (age, sex, BMI). Conclusions: At variance with what observed with OSA, presence and severity of CSA induced in healthy lowlanders by MA exposure seems unrelated to BP increase occurring in this condition, either during day or during night-time. This may depend either on pathophysiological differences between OSA and CSA or on inadequacies of indices characterizing breathing pattern during sleep.

PREDICTIVE POWER OF 24-HOUR AMBULATORY PULSE PRESSURE COMPONENTS FOR CARDIOVASCULAR MORTALITY IN DIFFERENT AGE AND HEART RATE STRATA DERIVED FROM DATA OF DUBLIN OUTCOME STUDY

Objective: It has been previously shown that average pulse pressure (PP), the systolic-diastolic blood pressure (BP) difference, measured with 24-hour ambulatory BP monitoring (24hABPM), can be expressed as a sum of two components: ‘elastic’ PP (elPP) and ‘stiffening’ PP (stPP) associated, respectively, with arterial stiffness (at the diastolic pressure) and its pressure dependence. The study objective was to determine PP, elPP and stPP (‘PP variables’) and assess their prognostic value in a large cohort of previously untreated subjects stratified by age and pulse rate (PR). Design and method: The study included untreated subjects assessed for hypertension in Dublin, Ireland, in whom 24hABPM records of adequate quality were obtained. The PP components were determined from the linear relationship between systolic- and diastolic BP using a model based on the nonlinear pressure-volume relationship in arteries that expresses stiffness-pressure relationship. Predictive power for cardiovascular (CV) mortality was expressed by hazard ratio (HR) determined using Cox regression models applied separately to PP and elPP & stPP (combined), adjusted for age, sex, BMI, smoking status, diabetes, previous CV disease, 24u200ah mean arterial pressure (MAP) and MAP dipping, and for the age and PR strata shown in the Table. Results: Of the 11,291 subjects included (age 54.4u200a±u200a14.5, 47% male) 566 CV deaths occurred during the follow-up period (mean 5.8 years). Meanu200a±u200aSD of PP, elPP and stPP were, respectively, 56.6u200a±u200a12.4, 49.0u200a±u200a9.8, and 7.6u200a±u200a6.9 mmHg, and elPP and stPP were uncorrelated (ru200a=u200a0.075). Table shows that the predictive power of elPP increased progressively with ageing, mainly for low PR. For age>=65 years elPP had greater predictive power than PP and stPP, especially for low PR. In contrast, for ageu200a<u200a50 and high PR, PP and stPP were stronger predictors than elPP, and for low PR none of PP variables had significant predictive power. Conclusions: PP components derived from 24hABPM may have greater predictive power for CV death than PP itself in elderly subjects. Studies investigating occurrence of an independent association of PP components with additional fatalities are required in order to demonstrate the specificity of these new measures. Figure. No caption available.

UPWARD-SHIFT AND STEEPENING OF THE BLOOD PRESSURE RESPONSE TO EXERCISE IN HYPERTENSIVE SUBJECTS AT HIGH ALTITUDE

Objective: Acute exposure to high altitude hypobaric hypoxia induces a blood pressure rise in hypertensive humans, both at rest and during exercise. It is unclear whether this phenomenon reflects specific blood pressure hyperreactivity or rather an upward shift of blood pressure levels. We aimed at evaluating the extent and rate of blood pressure rise during exercise in hypertensive subjects acutely exposed to high altitude, and how these alterations can be counterbalanced by antihypertensive treatment. Design and method: Fifty-five mild hypertensive subjects, double-blindly randomized to placebo or to a fixed-dose combination of an angiotensin-receptor blocker (telmisartan 80u200amg) and a calcium-channel blocker (nifedipine slow release 30u200amg), performed a cardiopulmonary exercise test at sea level and after the first night of stay at 3260 m altitude. Results: High altitude exposure caused both a 8 mmHg upward-shift (pu200a<u200a0.01) and a 0.4u200ammHg/mL/Kg/min steepening (pu200a<u200a0.05) of the systolic blood pressure/oxygen consumption relationship during exercise, independently of treatment (figure 1a). Telmisartan/nifedipine did not modify blood pressure reactivity to exercise, but downward shifted (pu200a<u200a0.001) the relationship between systolic blood pressure and oxygen consumption by 26 mmHg, both at sea level and at altitude (figure 1a). Muscle oxygen delivery, as evaluated by means of the relationship between oxygen consumption and workload, was not influenced by altitude exposure, but was higher on telmisartan/nifedipine than on placebo (pu200a<u200a0.01, figure 1b). Figure. No caption available. Conclusions: In hypertensive subjects exposed to high altitude we observed a hypoxia-driven upward-shift and steepening of the blood pressure response to exercise. The effect of the combination of telmisartan/nifedipine slow-release outweighed these changes, and was associated with better muscle oxygen delivery.

[OP.1C.05] DIFFERENT PROGNOSTIC RELEVANCE OF 24-HOUR SYSTOLIC AND DIASTOLIC BLOOD PRESSURE VARIABILITY IN DIFFERENT AGE STRATA. DUBLIN OUTCOME STUDY

Objective: 24-hour blood pressure (BP) variability (V) has been repeatedly shown to be associated with cardiovascular outcomes but in different studies this association was stronger for either systolic (S) or diastolic (D)BPV. Whether these discrepancies are age related remains an unresolved issue. Aim of this analysis was to separately assess the association of SBPV and DBPV with cardiovascular (CV) mortality in different age strata. Design and method: Dublin Outcome Study included untreated subjects assessed for hypertension followed on average for 5.8 years. Among them we selected 7950 individuals with daytime BP>=135/85 mmHg (age 54.8u200a±u200a13.9y, 49.2% males, BMI 27.4u200a±u200a4.6u200akg/m2). SBPV and DBPV were assessed from 24-hour ABPM with different methods (daytime standard deviation [SD], 24-hour weighted SD [wSD], average real variability [ARV]). The association of these variables with CV mortality (death certificates) was assessed in Cox regression models subdividing study subjects into three age groups, respectively young (<50 yrs), middle age (50–65 yrs) and elderly (>65 yrs) by age. Results: 410 CV deaths occurred among study subjects. Only DBPV was independently associated with CV mortality in the whole group. Adjusted hazard ratios (HR) for CV mortality associated with 1 SD change in SBPV and DBPV by age are summarized in the Table. Figure. No caption available. Conclusions: Short-term BP variability independently predicts cardiovascular mortality but the prognostic value of SBPV and DBPV varies according to age. Associations of DBPV with CV mortality were observed at all ages, being particularly significant in older subjects, while in young individuals SBPV was more relevant, possibly reflecting sympathetic activation and/or early vascular damage (e.g. increased arterial stiffness). More individualized application of BP variability components may thus increase their usefulness for cardiovascular risk stratification.

1B.11: ACCURACY OF DIFFERENT TYPES OF BLOOD PRESSURE MEASURING DEVICES AT HIGH ALTITUDE. DATA FROM HIGHCARE-ALPS STUDY.

Objective: Blood pressure (BP) measuring devices may become inaccurate at high altitude due to low barometric pressure. Aim of this study was to assess the changes in the accuracy of different types of BP measuring devices between sea level and high altitude, taking auscultatory measurements with mercury sphygmomanometer as reference. Design and method: In the frame of HIGHCARE-ALPS project, we obtained multiple BP measurements in 39 healthy, normotensive volunteers (age:36.4u200a±u200a8.5y,u200aM/F:21/18), using a mercury (MER, reference), an aneroid (ANE), and two validated oscillometric devices [one for home (OSC-HBP; AND UA-767PC) and one for ambulatory (OSC-ABP; AND TM2430)] BP monitoring, at sea level and during acute exposure to high altitude (4559m, 437–439 Torr). BP measurements with the different devices were performed sequentially on the same arm in random order, consistent under both study conditions. Results: Mean systolic (S) and diastolic (D)BP were higher at high altitude than at sea level (MER: 117.6/80.3 vs. 110.9/74.1 mmHg, pu200a<u200a0.001) The mean differences in SBP between MER (reference) and the other devices at baseline and high altitude were 1.7u200a±u200a6.5/0.6u200a±u200a7.1 (OSC-ABP), −3.1u200a±u200a5.3*/−3.8u200a±u200a6.3* (ANE) and −1.2u200a±u200a7.0/−5.0u200a±u200a6.7* (OSC-HBP) respectively. The corresponding differences for DBP were −3.9u200a±u200a5.9*/−4.5u200a±u200a6.5* (OSC-ABP), −2.2u200a±u200a5.1*−5.3u200a±u200a6.7* (ANE) and −4.8u200a±u200a7.6*/−1.8u200a±u200a7.1 (OSC-HBP), (mmHg, *pu200a<u200a0.01 vs. MER). The over or underestimations of BP values by tested devices as compared with MER were consistent and similar at sea level and high altitude, except for a greater underestimation of SBP by OSC-HBP (pu200a=u200a0.01), and of DBP by ANE (pu200a=u200a0.03) at altitude, and for a greater underestimation of DBP by OSC-HBP (pu200a=u200a0.02) at sea level. In spite of the statistical significance, the absolute changes in the size of error between sea level and high altitude never exceeded 4 mmHg. The distribution of mean between-device differences within the group was consistent between sea level and high altitude, with about 50% of subjects displaying between-devices differences always smaller than 5 mmHg (Figure). Figure. No caption available. Conclusions: BP measuring devices commonly used at sea level remain reasonably accurate at high altitude. We did not find consistent and clinically relevant changes in the accuracy of the tested devices caused by low barometric pressure at altitude.

508 EFFECT OF ANTIHYPERTENSIVE TREATMENT ON MORNING BLOOD PRESSURE SURGE. DETAILED ASSESSMENT BY COMBINATION OF 24 H AMBULATORY BLOOD PRESSURE MONITORING AND POLYSOMNOGRAPHY

Background: The rate of morning blood pressure rise, appears to significantly contribute to the higher morning incidence of cardiovascular events. Aim of our study was to compare the effects of once a day administration of Telmisartan (T) and Valsartan (V) in patients with mild to moderate hypertension, according to a randomized, double-blind design. Sleep was objectively quantified by polysomnography. Methods: 31 consecutive patients with essential hypertension were enrolled. Patients underwent 24 h ambulatory (A) BP monitoring and full polysomnography combined with beat by beat BP monitoring, under placebo (P), T 80 mg and V 160 mg. Results: At the end of each 2 month treatment period the rate of patients with controlled ASBP and ADBP with T and V, respectively, was 95% vs 50% for early morning hours; 62% vs 37% for 24 h ABP; 69% vs 31% for daytime ABP and 69% vs 50% for night-time ABP, (all T-to-V differences p < 0.05). The corresponding rates of ABP normalization with P were 50% for early morning hours, 0% for 24 h, 12% for daytime,14% for night-time ABP. The rate of clinic BP normalization was 81% vs 62% with T vs V respectively (p < 0.05). The proportion of dippers was 69% with P, 75% with T and 56% with V (T vs P and T vs V p < 0.05). Conclusions: T administration offered a significantly better clinic and 24 h ABP control than either P or V, also when focusing on early morning hours. T on morning administration was also associated with greater ABP dipping rate than P or V.