381. Intraindividual blood pressure responses to angiotensin-converting enzyme inhibition and angiotensin receptor blockade.
Stergiou GS, Efstathiou SP, Roussias LG, Mountokalakis TD.
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This study aims to test the hypothesis that in some hypertensive subjects the blood pressure (BP) response to angiotensin-converting enzyme inhibition differs from that to angiotensin receptor blockade (ARB); a responder to angiotensin-converting enzyme inhibition may not respond to ARB or the opposite. A randomized, open-label, crossover, comparative trial of lisinopril 20 mg compared with telmisartan 80 mg (5 weeks per treatment period) was conducted in 32 untreated hypertensives using 24-hour ambulatory BP monitoring. Subjects were classified as "responders" and "nonresponders" using an arbitrary threshold of ambulatory BP response (> or =10 mm Hg systolic or > or =5 diastolic) or the median response achieved by each drug. No difference was detected between the drugs in their effect on ambulatory BP (mean difference 1.2+/-7.1/0.7+/-5.1 mm Hg, systolic/diastolic). Significant correlations were found between the antihypertensive responses to the two drugs (r=0.77, p<0.001). Using the arbitrary response criterion, there was a difference between the drugs in the responses in 28%/13% of subjects (9/4 patients) for systolic/diastolic BP (19%/25% using the median response criterion). These data suggest that in some hypertensive patients the BP response to angiotensin-converting enzyme inhibition may fail to predict the response to ARB. It appears that there are differences in the antihypertensive action of angiotensin-converting enzyme inhibitors and ARBs that may be clinically important.
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382. Office and out-of-office blood pressure measurement in children and adolescents.
Stergiou GS, Alamara CV, Vazeou A, Stefanidis CJ.
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Office and out-of-office blood pressure measurements are being used for the diagnosis of hypertension in children and adolescents. The US National Heart, Lung, and Blood Institute have recently presented a new classification of blood pressure. On the basis of office measurements the 90th, 95th and 99th percentile for gender, age and height are used to classify children and adolescents as normotensive, pre-hypertensive and stage-1 or stage-2 hypertensive. Although auscultation using a standard mercury sphygmomanometer remains the recommended method, accumulating evidence suggests that ambulatory blood pressure monitoring is useful for the detection of white-coat hypertension and the prediction of target organ damage in children and adolescents. Studies have shown ambulatory blood pressure to be more reproducible than office measurements and normative tables for ambulatory measurements have been developed from cross-sectional studies in children and adolescents. In regard to home measurements in children, there are limited data from small trials showing lower blood pressure levels than daytime ambulatory blood pressure. In conclusion, ambulatory blood pressure monitoring is already finding a role as a supplementary source of information in children and adolescents, whereas at present home measurements should not be used for decision making in this population.
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383. Self monitoring of blood pressure at home.
Stergiou G, Mengden T, Padfield PL, Parati G, O'Brien E.
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Is an important adjunct to clinic measurements
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384. Out-of-office blood pressure in children and adolescents: disparate findings by using home or ambulatory monitoring.
Stergiou GS, Alamara CV, Kalkana CB, Vaindirlis IN, Stefanidis CJ, Dacou-Voutetakis C, Mountokalakis TD.
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385. Angiotensin receptor blockade in the challenging era of systolic hypertension.
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Systolic blood pressure is a major cardiovascular risk factor which is often associated with arterial stiffness. Markers of arterial stiffness, such as pulse pressure and carotid-femoral pulse wave velocity, have been proved independent predictors of cardiovascular risk. Recent evidence suggests that the renin-angiotensin system is involved in the pathogenesis of systolic hypertension and arterial stiffness. Outcome trials have shown impressive cardiovascular protection by reducing systolic blood pressure (BP) with drug treatment. However, in clinical practice systolic hypertension remains largely uncontrolled, first, because systolic BP goal is more difficult to be reached than diastolic and, second, because physicians are often reluctant to intensify treatment in patients with systolic BP close to 150 mmHg. Recent trials have focused on the effects of antihypertensive drugs not only on blood pressure, but also on pulse pressure and pulse-wave velocity. Blockade of the renin-angiotensin-aldosterone system, using angiotensin-converting enzyme inhibitors and more recently angiotensin receptor blockers, has been shown to provide beneficial effects on arterial stiffness that appear to be independent of their antihypertensive effects. Recent outcome trials have shown significant cardiovascular protection with angiotensin receptor blockers. These drugs have an excellent placebolike profile of adverse effects which is maintained when these drugs are combined with low-dose diuretics. Therefore, an angiotensin receptor blocker-based treatment strategy appears to be an attractive and evidence-based approach for the management of systolic hypertension, the reduction of arterial stiffness and the prevention of cardiovascular disease.
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386. Self blood pressure measurement at home: how many times?
Parati G, Stergiou G.
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387. New European, American and International guidelines for hypertension management: agreement and disagreement.
Stergiou GS, Salgami EV.
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Hypertension is a leading cause of morbidity and mortality worldwide and its control rates remain poor. In 2003, several official organizations presented new guidelines for hypertension management. These guidelines were developed using an evidence-based interpretation of the available information. Recommendations on hypertension prevention, diagnosis, patients' evaluation, decision to treat, antihypertensive drug selection and goals of treatment are included. There is considerable agreement among the new guidelines and only a few points of disagreement, that are of minor significance. Emphasis has been placed on the simplicity of recommendations in order for them to be easily applied by primary care physicians. This review focuses on the key messages of the 2003 guidelines and the areas of agreement and disagreement among them.
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388. Renin-angiotensin system blockade at the level of the angiotensin converting enzyme or the angiotensin type-1 receptor: similarities and differences.
Stergiou GS, Skeva II.
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The development of drugs which block the renin-angiotensin system (RAS) has been proven a major advance in cardiovascular medicine. Angiotensin converting enzyme (ACE) inhibitors, which block the formation of angiotensin II from the inactive angiotensin I, are widely used as first line treatment in hypertension, heart failure and diabetic nephropathy. More recently, selective antagonists of the angiotensin type-1 receptor (AT1R) have become available for clinical use. Accumulating evidence suggests that AT1R antagonists have similar effects to ACE inhibitors in hypertension, heart failure and diabetic nephropathy. Although ACE inhibitors and AT1R antagonists block the same system, experimental evidence suggest that their mechanisms of action differ in several respects, such as increased bradykinin and angiotensin 1-7 levels with ACE inhibitors and AT2R activation with AT1R antagonists. Nevertheless, the clinical significance of these differences remains largely unknown and, in practice, the only clear advantage of AT1R antagonists over ACE inhibitors is the absence of cough as a side effect. Recent clinical data suggest that combined ACE inhibition and AT1R antagonism offer additive effects in reducing blood pressure in hypertension, in reducing proteinuria in nephropathy and in improving prognosis in heart failure. Further evidence suggests that some hypertensive patients may have a good antihypertensive response with ACE inhibition but not with AT1R antagonism, or the reverse. These data suggest that these two drug classes have important similarities, because they act on the same system, but they also appear to have important differences, which are not only of theoretical but also of clinical importance.
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389. White coat effect in treated versus untreated hypertensive individuals: a case-control study using ambulatory and home blood pressure monitoring.
Stergiou GS, Efstathiou SP, Argyraki CK, Roussias LG, Mountokalakis TD.
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390. Diagnostic value of strategy for the detection of white coat hypertension based on ambulatory and home blood pressure monitoring.
Stergiou GS, Alamara CV, Skeva II, Mountokalakis TD.
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An algorithm has been proposed for the detection of white coat hypertension among subjects with elevated blood pressure (BP) on at least three clinic visits using home BP monitoring (screening test) and, if this is low, ambulatory BP monitoring (diagnostic test). This study aims to test this strategy in practice. The proposed algorithm was applied in 133 untreated subjects with elevated BP assessed in a previous prospective study using repeated clinic, home and ambulatory BP measurements. The proportions of detected and missed cases of white coat hypertension and the diagnostic value of the algorithm were calculated. By applying the algorithm, 99 subjects (74%) were found eligible for home measurements and 35 (26%) for ambulatory monitoring. There were 38 subjects with white coat hypertension (38%), of whom 15 (39%) were not detected by the proposed strategy. The sensitivity, specificity, and the positive and negative predictive value of the algorithm to diagnose white coat hypertension were 61, 81, 66 and 77%, respectively. Of the 34 subjects with normal BP on the third clinic visit, 15 (42%) had elevated home and/or ambulatory BP. These data suggest that, using the proposed strategy, many white coat hypertensives may remain undetected and may receive unnecessary long-term drug treatment. Therefore, more research is needed on the optimal strategy for detecting white coat hypertension in clinical practice.
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391. Home or self blood pressure measurement? What is the correct term?
Stergiou GS, Efstathiou SP, Alamara CV, Mastorantonakis SE, Roussias LG.
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392. Aggressive blood pressure control in general practice (ABC-GP) study: can the new targets be reached?
Stergiou GS, Karotsis AK, Symeonidis A, Vassilopoulou VA.
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Based on outcome trials, guidelines for hypertension management recommend lower blood pressure (BP) goals using an individualized treatment strategy (IND) and referral to a specialist of patients uncontrolled after 6 months of treatment. This study aimed to evaluate the performance of General Practitioners (GPs) in reaching the recommended BP goals using the IND, or a stepwise treatment strategy (STEP) as used in the outcome trials. Trained GPs were randomized to reach the BP goals within 6 months using the IND or a STEP strategy in untreated or treated uncontrolled hypertensives. In all, 24 GPs recruited 528 patients of whom 443 were analysed (mean age 65+/-9 years, 42% men, 70% treated, STEP/IND 12/12 GPs, 231/211 patients). After 6 months, 83% of the patients had reached the diastolic BP goal, whereas only 51% the systolic (P<0.0001 for difference). Factors associated with uncontrolled systolic BP were diabetes, age >60 years and triple antihypertensive therapy at baseline. A faster BP reduction was achieved during the first 3 months using the STEP strategy, but at the cost of using more drugs (combination therapy in 68/59% for STEP/IND, P=0.06). At 6 months similar rates of control were achieved with the two strategies. In conclusion, in primary care the diastolic BP goal can be reached within 6 months in the majority of patients, whereas systolic BP remains uncontrolled in 50% of the cases. The IND should be the recommended treatment strategy, but further investigation is required on the reasons for treatment failure and the optimal strategy for its improvement.
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393. Which is the correct term for blood pressure measurements taken at home?
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The terms 'self-blood pressure' and 'home blood pressure' are being used to describe measurements of blood pressure taken by the patients at home. However, home measurements are not always self-measurements, because these are often taken by the patients' relatives. There is little evidence on the effect of self-measurement on the level of blood pressure taken using automated electronic devices. In regard to clinic blood pressure, two studies using automated devices found no difference between measurements taken by physicians or patients themselves, irrespective of whether self-measurements were taken in the presence or the absence of the physician. In regard to home blood pressure, one randomized crossover trial showed no difference between home measurements taken by the patients themselves or their relatives using fully automated devices. On the other hand, many studies have consistently shown home blood pressure to be lower than clinic pressure. Taken together these data suggest that self-measurement has no effect on the level of blood pressure, either in the clinic, or at home. The lower level of home in comparison to clinic blood pressure seems to be exclusively attributed to the effect of the different setting, rather than the person who is taking measurements. Therefore the term 'self blood pressure' seems to be a misnomer, whereas the term 'home blood pressure' represents a more appropriate term for home measurements taken by patients or their relatives.
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394. Blood pressure- and pulse pressure-lowering effects, trough:peak ratio and smoothness index of telmisartan compared with lisinopril.
Stergiou GS, Efstathiou SP, Roussias LG, Mountokalakis TD.
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395. Comparison of the smoothness index, the trough : peak ratio and the morning : evening ratio in assessing the features of the antihypertensive drug effect.
Stergiou GS, Efstathiou SP, Skeva II, Baibas NM, Roussias LG, Mountokalakis TD.
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396. European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement.
O'Brien E, Asmar R, Beilin L, Imai Y, Mallion JM, Mancia G, Mengden T, Myers M, Padfield P, Palatini P, Parati G, Pickering T, Redon J, Staessen J, Stergiou G, Verdecchia P.
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397. Self measured and ambulatory blood pressure in assessing the 'white-coat' phenomenon.
Parati G, Stergiou GS.
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398. Genomic and chromosomal organization of Ty1- copia-like sequences in Olea europaea and evolutionary relationships of Olea retroelements.
Stergiou G, Katsiotis A, Hagidimitriou M, Loukas M.
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The Ty1- copia-like retrotransposon is one of the commonest class of transposable elements in the plant kingdom, often comprising several percent of the total DNA content. We aimed to study the evolutionary relationships of Olea retroelements, using part of the reverse transcriptase domain, as well as the genomic and chromosomal organization of these sequences in Olea europaea chromosomes and their transcription activity and copy number. Fourteen clones, that were isolated from four different species, were sequenced and a phylogenetic tree was constructed based on their predicted amino acids. Five clones derived from O. europaea were clustered together with a 87% nucleotide sequence homology and two Olea oleaster clones showed 98% sequence homology. The rest of the clones showed heterogeneity among them, leading to a common ancestral transposon that existed before the genus arose. The Ty1- copia-like sequences have a dispersed genomic organization, physically distributed on all chromosomes, showing minor clustering in some cases and low copy numbers in the smallest chromosome pair. The total copy number in the O. europaea genome was estimated by dot blotting to be 40,000 in a haploid nucleus, but a number of these are non-functional since the sequenced clones contained stop codons and frame-shifts. Some Ty1- copia-like copies, present in O. europaea, were found to be methylated, while no differences in methylation were observed between DNA isolated from young leaves and callus-suspension cultures.
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399. Assessment of drug effects on blood pressure and pulse pressure using clinic, home and ambulatory measurements.
Stergiou GS, Efstathiou SP, Skeva II, Baibas NM, Kalkana CB, Mountokalakis TD.
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This study investigated the differences in the effect of an angiotensin converting enzyme inhibitor (ACEI) compared with an angiotensin receptor blocker (ARB) on blood pressure (BP) and pulse pressure (PP) measured in the clinic (CBP and CPP, respectively), at home (HBP, HPP) and with ambulatory monitoring (ABP, APP). Twenty-seven hypertensive patients were randomised to receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks, and were subsequently crossed-over to the alternative treatment for a second 5-week period. Measurements of CBP, 24-h ABP and 5-days HBP were performed before randomisation and at the end of each treatment period. All measurement methods showed that lisinopril was more effective than losartan in reducing BP. However, the difference between the two drugs was demonstrated with greater precision using HBP (P<0.001) than 24-h ABP (P<0.01), whereas the poorest precision for demonstrating this difference was provided by CBP (P<0.05). Lisinopril was also found more effective than losartan in reducing HPP (P=0.01) and 24-h APP (P=0.03) whereas no such a difference was detected using measurements of CPP. It was concluded that the antihypertensive drugs may differ in their effects not only on BP, but also on PP. HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP. Clinic measurements seem to be the least reliable method, particularly in the detection of differences in PP.
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400. Determinants of arterial stiffness in Greek and French hypertensive men.
Achimastos A, Benetos A, Stergiou G, Argyraki K, Karmaniolas K, Thomas F, Mountokallakis T.
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The aim of the present study was to assess the main determinants of arterial stiffness in Greek and French middle-aged, hypertensive men, by using pulse wave velocity (PWV) measurements, which is an established method of quantification of arterial stiffness. The study was performed in 83 consecutive Greek and 79 consecutive French untreated male hypertensive outpatients aged 45-65 years. French subjects were examined in Paris at the "Centre d'Investigations Préventives et Cliniques" (the IPC Center). Greek patients were examined in Athens at the hypertension outpatient clinic in Sotiria Hospital (University of Athens). In both Greek and French hypertensive subjects, aortic stiffness was determined by the same parameters: age, blood pressure and heart rate (HR) explained approximately 40% of the aortic PWV variations, whereas lipids, triglycerides and tobacco smoking were not significant associated with aortic stiffness. After multivariate adjustments, Greek hypertensives had higher aortic stiffness as compared to the French patients by 1.2 m/s (approximately 10%); p < 0.001. Greek hypertensive subjects had also a higher body weight, waist, HR and prevalence of smoking. However, among all these factors only HR had a significant effect on PWV. Also after adjustment for HR, the difference in PWV between the two populations persisted. In conclusion, in two different populations, stiffness seems to be regulated by the same major factors. The higher aortic stiffness found in Greek hypertensives may be explained by the presence of other non-evaluated risk factors and/or patient selection differences.
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