N. Vogiatzakis

Biomarkers of Atrial Fibrillation in Hypertension

BACKGROUNDnAtrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia globally and substantially increases the risk for thromboembolic disease. Albeit, 20% of all cases of AF remain undiagnosed. On the other hand, hypertension amplifies the risk for both AF occurrences through hemodynamic and non-hemodynamic mechanisms and cerebrovascular ischemia. Under this prism, prompt diagnosis of undetected AF in hypertensive patients is of pivotal importance.nnnMETHODnWe conducted a review of the literature for studies with biomarkers that could be used in AF diagnosis as well as in predicting the transition of paroxysmal AF to sustained AF, especially in hypertensive patients.nnnRESULTSnPotential biomarkers for AF can be broadly categorized into electrophysiological, morphological and molecular markers that reflect the underlying mechanisms of adverse atrial remodeling. We focused on P-wave duration and dispersion as electrophysiological markers, and left atrial (LA) and LA appendage size, atrial fibrosis, left ventricular hypertrophy and aortic stiffness as structural biomarkers, respectively. The heterogeneous group of molecular biomarkers of AF encompasses products of the neurohormonal cascade, including NT-pro BNP, BNP, MR-pro ANP, polymorphisms of the ACE and convertases such as corin and furin. In addition, soluble biomarkers of inflammation (i.e. CRP, IL-6) and fibrosis (i.e. TGF-1 and matrix metalloproteinases) were assessed for predicting AF.nnnCONCLUSIONnThe reviewed individual biomarkers might be a valuable addition to current diagnostic tools but the ideal candidate is expected to combine multiple indices of atrial remodeling in order to effectively detect both AF and adverse characteristics of high risk patients with hypertension.

ACUTE DETRIMENTAL EFFECTS OF E-CIGARETTE AND TOBACCO CIGARETTE SMOKING ON BLOOD PRESSURE AND SYMPATHETIC NERVE ACTIVITY IN HEALTHY SUBJECTS

Objective: This study aimed to assess the acute effects of tobacco cigarettes, e-cigarettes and sham smoking on blood pressure and sympathetic nervous system in healthy subjects. Design and method: We studied 10 normotensive male habitual smokers (mean age 33 years, body mass index: 24.1u200akg/m2, office blood pressureu200a=u200a117/72 mmHg) free of cardiovascular disease. The study design was randomized and placebo controlled with 3 experimental sessions. Subjects smoked 2 tobacco cigarettes containing 1.1u200amg nicotine or simulate smoking (sham smoking) with the 2 cigarettes separated by 5 minutes, while 45 minutes after finishing the second cigarette, subjects smoked a third cigarette or sham cigarette. Additionally, participants smoked e-cigarettes for a period of 5 and 30 minutes. Sympathetic drive was assessed by muscle sympathetic nerve activity (MSNA) (baroreflex-dependent) and skin sympathetic nerve activity (SSNA) (baroreflex-independent). Results: After the first, second and third tobacco cigarette smoking there was an increase in mean arterial pressure (by 11.2u200a±u200a1.4%, 12.3u200a±u200a1.3% and 13.1u200a±u200a1.4%, respectively, pu200a<u200a0.05 for all) and heart rate (by 25.1u200a±u200a3.7%, 26.3u200a±u200a2.7% and 25.9u200a±u200a3.7%, respectively, pu200a<u200a0.05 for all). Similarly e-cigarette smoking at 5 and 30 minutes was accompanied by augmentation of mean arterial pressure (by 10.9u200a±u200a1.2% and 12.8u200a±u200a1.4%, respectively, pu200a<u200a0.05 for both) and heart rate (by 22.5u200a±u200a3.3% and 23.9u200a±u200a3.8%, respectively, pu200a<u200a0.05 for both). The first, second and third tobacco cigarette smoking was accompanied by lower MSNA (by 28.1u200a±u200a4.4%, 29.6u200a±u200a5.3% and 30.1u200a±u200a5.2%, respectively, pu200a<u200a0.05 for all), whereas SSNA was increased (by 98.2u200a±u200a19.4%, 100.2u200a±u200a22.7% and 101.5u200a±u200a21.6%, respectively, pu200a<u200a0.05 for all). Additionally, e-cigarette smoking at 5 and 30 minutes caused a decrease in MSNA (by 26.9u200a±u200a3.6%, and 28.3u200a±u200a5.1%, respectively, pu200a<u200a0.05 for both), and an augmentation in SSNA (by 97.9u200a±u200a20.1% and 100.9u200a±u200a20.6%, respectively, pu200a<u200a0.05 for both). Sham smoking was devoid of any effects on blood pressure, MSNA and SSNA. Conclusions: E-cigarette smoking acutely increases blood pressure and has a detrimental effect on sympathetic nerve activity regulation similar to tobacco smoking in healthy subjects.

REDUCED BLOOD PRESSURE VARIABILITY AS A PREDICTOR OF CARDIAC EVENTS AFTER MYOCARDIAL INFARCTION: A 6 MONTHS FOLLOW-UP STUDY

Objective: The impact of blood pressure variability (BPV) on cardiac function has been mainly examined through the prism of congestive heart failure and hypertension, but not in the setting of an acute coronary syndrome (ACS). The aim of this study is to determine the association between in-hospital short-term BPV and the development and aggravation of cardiac dysfunction in patients with acute myocardial infarction (AMI). Design and method: A total population of 57 AMI patients [74.5% male; mean age: 67.56 years;75.4% hypertensives]underwent 24hr ambulatory BP measurement during hospitalization.At 6 months a follow-up was scheduled for each patient in order to collect data on hospitalizations for heart failure (HF), but also to assess the overall cardiovascular outcome.The latter was defined as the composite end-point ofhospitalizations for heart failure (nu200a=u200a8), decline in ejection fraction (EF%) compared to the in-hospital value (nu200a=u200a11), deterioration of NYHA class (nu200a=u200a3) and new onset of heart failure symptoms (nu200a=u200a2). In-hospital BPV was assessedusing standard deviation (SD) and average real variability (ARV). The study population was divided intoa STEMI group (nu200a=u200a24) and a non-STEMI (nu200a=u200a33) one. Results: BPV was not associated with hospitalizations for HF. However, when the composite end-point was assessed, ARV of systolic BP demonstrated a significant negativeassociation [Bu200a=u200a-0.430; odds ratio, 0.651; CI, 0.473–0.895 (Pu200a=u200a0.008)]in the total population. A relatively significant predictive roleof ARV was shown after splitting the population into the STEMI [Bu200a=u200a−0.531; odds ratio, 0.588; CI, 0.339–1.019 (Pu200a=u200a0.058)]and non-STEMI group[Bu200a=u200a−0.4; odds ratio, 0.670; CI, 0.443–1.014 (Pu200a=u200a0.058)]. Multinomial logistic regression analysis of incidence of cardiovascular events highlightedsystolic BP ARVas the onlyindependent predictor during a 6-month follow-up [Bu200a=u200a−0.508; odds ratio, 0.602; CI, 0.407–0.891 (Pu200a=u200a0.011)] regardless the ACS type. Conclusions: In the setting of ACS, reduced in-hospital systolic BP ARV was associated with cardiovascular morbidity during the 6 months of follow-up. This finding could be attributed to a dysautonomic state of the cardiovascular system related to the pathophysiology of ACS, linking BP regulation mechanisms to worse overall outcome in this high risk setting.

BLOOD PRESSURE VARIABILITY AND CLINICAL CHARACTERISTICS OF PATIENTS HOSPITALIZED FOR ACUTE MYOCARDIAL INFARCTION

Objective: The aim of the present study was to assess blood pressure variability (BPV) in patients hospitalized for acute myocardial infarction. Design and method: We studied 75 patients (76% males, age 65u200a±u200a13 years) who were hospitalized because of ST-elevation myocardial infarction (STEMI) and Non ST–elevation myocardial infarction (NSTEMI). All patients underwent baseline estimation of clinical and laboratory parameters during their hospitalization. Additionally, BPV was estimated based on double daily measurements of BP during hospitalization and with 24-hour ambulatory BP monitoring during the third day of hospital stay. The parameters of BPV analyzed were: a) standard deviation (SD) of systolic BP (24-h, daytime and nighttime), b) SD of diastolic BP (24-h, daytime and nighttime) and c) the coefficient of variation (CV) of systolic BP (24-h, daytime) and d) the average real variability (ARV) of systolic and diastolic BP across 24-h. Results: From the total population, 20% had family history of cardiovascular events, 72% were hypertensives, 32% had diabetes, 51% were smokers and 32% had previous history of coronary artery disease. Regarding the type of myocardial infarction, 37% were admitted for STEMI and 55% had coronary revascularization. Focusing on the mean systolic and diastolic BP and their SD the values were 72u200a±u200a6.1mmHg, 127u200a±u200a11.4mmHg and 74.5u200a±u200a6.5mmHg, respectively. From the ambulatory BP the daytime, nighttime and total SD of systolic BP was 11.3u200a±u200a2.8mmHg, 9.8u200a±u200a3.1mmHg and 11.7u200a±u200a2.9mmHg, respectively. Moreover, ARV was 9.31u200a±u200a2.1mmHg while CV was 10.21u200a±u200a26 %. The type of MI (STEMI and NSTEMI) was significantly related to systolic and diastolic ARV (ru200a=u200a0.29, pu200a=u200a0.012 and ru200a=u200a0.28, pu200a=u200a0.014, respectively). Conclusions: In patients admitted for acute myocardial infarction there is a relationship between the ARV and the type of myocardial infarction. These findings suggest differential impact of hemodynamic load on the cardiovascular system in patients with STEMI and NSTEMI.

IN-HOSPITAL BLOOD PRESSURE VARIABILITY AS A PREDICTOR OF RENAL IMPAIRMENT IN PATIENTS WITH MYOCARDIAL INFARCTION: A 6-MONTH FOLLOW-UP STUDY

Objective: Recent data have associated blood pressure variability (BPV) with subclinical renal damage, acute renal injury and progression of chronic kidney disease but not in the setting of an acute coronary event. The aim of this study is to determine the impact of in-hospital short-term BPV on future renal impairment in patients suffering an acute myocardial infarction (AMI). Design and method: A total population of57 AMI patients [74.5% male; mean age: 67.56 years;75.4% hypertensives; 28.1% chronic kidney disease (GFRu200a<u200a60u200aml/min on admission)]underwent 24hr ambulatory BP measurement during their hospitalization. At 6months a follow-up was scheduled foreach patient in order to estimate their present renal function. Renal impairment was defined as a decline in GFR value between a discharge and a 6-month visit, which were calculated by using the Cockcroft-Gault Equation. In-hospital BPV was derived by assessment of standard deviation (SD), weighted-SD (SDw), average real variability (ARV) and coefficient of variability (CV). The study population was divided intoa STEMI group (nu200a=u200a24) and a non-STEMI(nu200a=u200a33) one. Results: After analysis of BPV indices, 6-month renal impairment was significantly associated with increased SBP CV[odds ratio, 0.467; CI, 0.218–1.003 (Pu200a=u200a0.051)]. This observation was met only in the STEMI group. A multinomial logistic regression analysiswas conducted for this group of patients, in which SBP CV demonstrated a significant prognostic role of renal impairment [odds ratio, 0.623; CI, 0.394–0.987 (Pu200a=u200a0.044)], independently of age, gender and24hr SBP. Conclusions: In the setting of STEMI, assessment of BPV using SBP CV has a prognostic role in the future development of renal dysfunction. This observation, if confirmed by further studies, could influence the therapeutic approach of ACS in terms of BP management.

IN-HOSPITAL BLOOD PRESSURE VARIABILITY AS A PREDICTOR OF CARDIO-RENAL OUTCOMES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Objective: Data are scarce regarding the possible prognostic role of blood pressure variability (BPV) in the setting of acute coronary syndrome (ACS). The aim of this study is to determine the impact of in-hospital short-term BPV on cardiovascular outcomes and renal function in patients suffering an acute myocardial infarction (AMI). Design and method: A total population of 150 AMI patients (78.7% male; mean age: 63.57 years;68% hypertensives) underwent 24hr ambulatory BP measurement during their hospitalization. Systolic BPV was derived by coefficient of variability (CV). The study population was divided intoa STEMI group (nu200a=u200a72) and a non-STEMI (nu200a=u200a78) one. Cardiovascular outcomes included: new onset of ACS, pulmonary edema, hypertensive emergency, life threatening arrhythmias, whereas worsening of renal function (WRF) was defined as a reduction of GFRu200a>u200aoru200a=u200a25% according to the RIFLE criteria.No deaths or strokes occurred during the study. Results: In the total study population a significant positive association was demonstrated between SBP CV andthe incidence of total cardiovascular outcomes [odds ratio, 1.240; CI, 1.023–1.503 (Pu200a=u200a0.028)]as well asWRF[odds ratio, 1.394; CI, 1.109–1.753 (Pu200a=u200a0.004)]. Results for the STEMI group were similar regarding both cardiovascular outcomes [odds ratio, 1.38; CI, 1.066–1.794 (Pu200a=u200a0.015)]and WRF [odds ratio, 1.666; CI, 1.126–2.465 (Pu200a=u200a0.011)]. However, the non-STEMI group failed to demonstrate any significant associations. Finally, we conducted a multinomial logistic regression model for the STEMI group, where SBP CV showed relative significance as a predictor of cardiovascular outcomes [odds ratio, 1.317; CI, 0.994–1.746 (Pu200a=u200a0.056)], independently of age, gender and history of hypertension, diabetes mellitus or coronary heart disease. Conclusions: In the setting of STEMI, assessment of systolic BPV using systolic BP CV could have a prognostic role of in-hospital cardio-renal outcomes suggesting a clinical need for further individualization of BP regulation in the integrative ACS management.

Cardiovascular morbidity of severe resistant hypertension among treated uncontrolled hypertensives: a 4-year follow-up study

Data regarding the prognosis of resistant hypertension (RHTN) with respect to its severity is limited. We investigated the cardiovascular risk of severe RHTN in a prospective observational study. A cohort of 1700 hypertensive patient with treated uncontrolled HTN was followed for a mean period of 3.6u2009±u20091.8 years. At baseline, standard clinical and laboratory workup was performed, including testing for secondary causes of RHT where applicable. Three groups were identified depending on presence of RHTN (office-based uncontrolled HTN under at least three drugs including a diuretic) and levels of office systolic blood pressure (BP): 1187 patients (70%) without RHTN, 313 (18%) with not-severe RHTN (systolic BPu2009<u2009160u2009mmHg) and 200 (12%) with severe RHTN (systolic BPu2009≥u2009160u2009mmHg). Endpoint of interest was cardiovascular morbidity set as the composite of coronary heart disease and stroke. During follow-up, incidence rates of cardiovascular events per 1000 person-years were 7.1 cases in the non-RHTN group, 12.4 cases in the not-severe RHTN group and 18 cases in the severe RHTN group. Unadjusted analysis showed that compared to uncontrolled patients without RHTN, patients with not-severe RHTN exhibited a similar risk but patients with severe RHTN had a significantly higher risk, by 2.5 times (CI: 1.28–4.73, pu2009=u20090.007). Even after multivariate adjustment for established risk factors including BP levels and isolated systolic HTN, severe RHTN remained as an independent predictor of the cardiovascular outcome (OR: 2.30, CI: 1.00–5.29, pu2009=u20090.05). In conclusion, among treated yet uncontrolled hypertensive patients, severe RHTN exhibits a significantly higher cardiovascular risk indicating the need for prompt management.

[BP.07.03] EXAGGERATED EXERCISE BLOOD PRESSURE RESPONSE IS ACCOMPANIED BY INCREASED SYMPATHETIC ACTIVITY AND ARTERIAL STIFFNESS IN SUBJECTS WITH HIGH NORMAL BLOOD PRESSURE

Objective: The clinical importance of a hypertensive response to exercise (HRE) in subjects with high normal blood pressure (BP) is not fully elucidated, while sympathetic overactivity and arterial stiffening are linked with adverse cardiovascular prognosis. The aim of this study was to assess the relation of HRE with sympathetic drive as assessed by muscle sympathetic nerve activity (MSNA) and arterial stiffness in subjects with high normal BP. Design and method: 20 subjects with high normal office BP [defined as office systolic BP=130–139 mmHg and office diastolic BP=85–89 mmHg (age: 52u200a±u200a9 years, 12 males, office BP: 135/85 mmHg, 24-hour BP: 115/73 mmHg)] with a negative treadmill exercise test (Bruce protocol) were divided into those with HRE (n=6) (peak exercise systolic BPu200a>u200a=210mmHg in men and >=190 mmHg in women) and those without HRE (nu200a=u200a14). Arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) values. In all participants sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography). Results: Subjects with a HRE compared to those without exhibited higher waist circumference (109.2u200a±u200a5.3 vs 94.8u200a±u200a9.1u200acm, pu200a=u200a0.001) and were characterized by greater levels of carotid to femoral PWV (8.5u200a±u200a0.7 vs 7.1u200a±u200a0.9u200am/sec, pu200a<u200a0.001) and sympathetic nerve traffic as reflected by MSNA levels (42.1u200a±u200a1.5 vs 33.1u200a±u200a1.9 bursts per 100 heart beats, pu200a<u200a0.001), while did not differ regarding metabolic profile and left ventricular mass index (pu200a=u200aNS). In the total population, peak exercise systolic BP was related to 24-h systolic BP (ru200a=u200a0.229, pu200a<u200a0.05), PWV (ru200a=u200a0.218, pu200a=u200a0.002), and MSNA (ru200a=u200a0.214, pu200a<u200a0.05). Moreover, MSNA was related to waist circumference (ru200a=u200a0.33, pu200a=u200a0.004) and office systolic BP levels (ru200a=u200a0.31, pu200a<u200a0.05) but there was no association with PWV values (pu200a=u200aNS). Conclusions: In subjects with high normal BP, a HRE indentifies a state of arterial stiffening and sympathetic overdrive, as reflected by increased PWV and MSNA levels respectively. These finding suggest that exercise testing provides additional clinical information regarding the vascular status and modulation of sympathetic tone in this setting.