Ignite Creation Date:
2024-05-06 @ 7:37 AM
Last Modification Date:
2024-10-26 @ 11:50 AM
Study NCT ID:
NCT02563379
Status:
UNKNOWN
Last Update Posted:
2015-10-01
First Post:
2015-09-28
Brief Title:
Association of Dipping Pattern or Early Morning Surge of BP With Asymptomatic Episodes of Paroxysmal Atrial Fibrillation in Subjects With Hypertension DIMOSPAF
Sponsor:
Evangelismos Hospital
Organization:
Evangelismos Hospital
Study Overview
Official Title:
Association Between Circadian Blood Pressure Patterns With Asymptomatic Episodes of Paroxysmal Atrial Fibrillation in Hypertensive Subjects
Status:
UNKNOWN
Status Verified Date:
2015-09
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DIMOSPAF
Brief Summary:
The goals of our study are to determine athe association between abnormal circadian BP and the development of paroxysmal AF in hypertensive patients bat which level of TOD paroxysmal AF episodes are detected in hypertensive subjects cif there is any association between systolic andor diastolic BP levels with AF occurrence dwhether the mean heart rate during a 24-hr interval is associated with the development of paroxysmal AF and finally eexamine the relationship between a wide PP and asymptomatic AF episodes in patients with HTN
Detailed Description:
Atrial fibrillation also known as AF or Afib is an abnormal and irregular heart rhythm in which electrical signals are generated chaotically throughout the upper chambers atria of the heart According to the NICE clinical guidelines a patient who experiences recurrent two or more AF episodes that terminate spontaneously without any treatment in less than seven days and usually within 48 hours is classified as having paroxysmal AF It has been shown that paroxysmal AF comprises approximately between 25 and 62 of cases of AF and it is estimated that both its incidence and prevalence are likely to rise as the worldwide population ages dramatically over the next twenty years Interestingly hospitalizations due to AF have increased sharply in the US during the last decade posing thereby a heavy economic burden on the health care system and society
Likewise hypertension HTN also constitutes a major public health problem globally and its prevalence is set to increase owing to widespread population ageing This epidemiological trend is especially prevalent in rapidly developing countries where early routine screening at any point of health care is underutilized among risk subjects due to several perceived barriers Moreover HTN awareness is critical for optimal BP control since under-diagnosis under-treatment andor un-treatment of high BP levels can have deleterious effects on the cardiovascular system In addition HTN is the single most important risk factor for cerebrovascular stroke and it has been clearly demonstrated that it is also associated with structural and functional changes in the myocardium that favor the development of AF further increasing the risk of thromboembolism Among those alterations left ventricular hypertrophy LVH impaired ventricular filling left atrial enlargement and slowing of atrial conduction velocity have been identified as important heralds of cardiovascular morbidity and mortality More specifically since HTN and AF are two conditions that often co-exist especially in patients with advanced age the risk for considerable morbidity and mortality is increased even more which points towards the significance that optimal BP control holds in the prevention of cardiovascular events To our knowledge in the Framingham Heart Study after controlling for age and other predisposing conditions HTN and diabetes emerged as the only cardiovascular risk factors predicting AF
It has also been suggested that nocturnal HTN and non-dipping of BP during sleep are distinct entities that often occur together and are regarded as important harbingers of poor cardiovascular prognosis Recently Pierdomenico et al showed that non-dipper sustained hypertensives have a two-fold greater risk of developing AF than dipper ones This may be due to the fact that nighttime HTN may be a powerful determinant of long-standing left ventricular diastolic dysfunction which subsequently increases atrial stretch Furthermore it has been observed that nighttime hemodynamics are associated with higher sympathetic and reduced vagal activity which may trigger AF Additionally sympathetic activation is associated with the stimulation of the renin-angiotensin-aldosterone axis RAAA which leads to increased left ventricular diastolic preload both atrial and ventricular fibrosis exerting thus direct cellular electrophysiological effects Besides scientists suggested that nighttime HTN is better associated with cardiovascular target organ damage TOD as compared with the non-dipping pattern
According to the most recent guidelines of the ESH the presence of microalbuminuria increased pulse wave velocity LVH on echocardiogram and carotid plaques detected during carotid ultrasonography constitute markers of asymptomatic organ damage and it has been clearly demonstrated from multiple studies that they can predict CV mortality independently of SCORE stratification
In our study we will try to investigate whether abnormalities in the circadian rhythm of BP such as extreme dipping or non-dipping pattern andor morning surge in hypertensive subjects with or without TOD are associated with the development of new-onset paroxysmal AF
24-hr ambulatory BP monitoring ABPM along with the 24-hour blood pressure monitors with AF detector will help us to examine the incidence of AF in extremely dippers or non-dippers andor patients exhibiting a morning surge in BP with or without TOD Some of the questions that we aim to answer while conducting this study are whether an asymptomatic AF episode is more commonly detected in extreme dippers non-dippers or morning surgers during daytime or during nighttime or whether TOD is associated with asymptomatic AF episodes
Importantly Iqbal et al demonstrated that there is an association between AF and nighttime DBP On top of that during the past decade a research study conducted in 546 hypertensive subjects aged 60 years of age and who were followed-up for 92 years showed that DBP whether 24-hr mean daytime mean or nighttime mean provided the most incremental value for the prediction of morbid events Thereby we want to examine if AF episodes have any association with the 24hr systolic and the diastolic blood pressure DBP levels It would also be interesting to observe for any associations between AF occurrence and the mean 24-hr ABPM and office heart rate HR
Moreover it has been showed that pulse pressure PP determines left atrial enlargement in non-dipper patients with never-treated essential HTN Thus in our study we will also examine whether a wide PP is associated with silent AF episodes in treated hypertensive subjects
Summarizing the goals of our study are to determine athe association between abnormal circadian BP and the development of paroxysmal AF in hypertensive patients bat which level of TOD paroxysmal AF episodes are detected in hypertensive subjects cif there is any association between systolic andor diastolic BP levels with AF occurrence dwhether the mean heart rate during a 24-hr interval is associated with the development of paroxysmal AF and finally eexamine the relationship between a wide PP and asymptomatic AF episodes in patients with HTN
Study Population We will evaluate all adult patients referred by their family physicians to the Hypertension and Cardiovascular Prevention Outpatient Clinic at Evangelismos General Hospital in Athens from June 2015 to present
All patients with an average office systolic BP 140 mmHg andor an average diastolic BP 90 mmHg on three consecutive visits are considered as having essential HTN Furthermore individuals under treatment with one or more antihypertensive drug are also enrolled in the study
Objectives Primary endpoint
To investigate whether nighttime BP patterns extreme dipping normal dipping or reduced dipping and non-dipping including risers or early morning surge are associated with the detection of paroxysmal AF in hypertensive subjects
Further definitions Normal diurnal systolic and diastolic BP pattern arterial BP has a daily variation characterized by substantial reductions during sleep a rapid rise upon awakening and increased variability during the awake period in ambulant normal subjects and hypertensive patients
Reduced diurnal systolic and diastolic BP pattern nocturnal systolic andor DBP fall from 1 to 10 of daytime values or nightday systolic andor diastolic BP ratio 1 and 09
Nocturnal HTN increased absolute level of night time systolic andor diastolic BP 12070 mmHg19 Dipping pattern is defined as daytime-nighttime BPdaytime BP reduction - based on either ABP or home BP HBP monitoring- greater than 10 for systolic andor diastolic BP Nighttime HTN is defined as nighttime ABP or HBP 12575 mmHg systolic andor diastolic
Non-dipping and rising no reduction or increase in nocturnal systolic andor diastolic BP or nightday systolic andor diastolic BP ratio 1
Extreme dipping marked nocturnal systolic andor diastolic BP fall20 of daytime systolic andor diastolic values or nightday systolic andor diastolic BP ratio 08
Morning surge excessive systolic andor diastolic BP elevation rising in the morning
Secondary endpoints
To detect asymptomatic and intermittent AF using a 24h ABPM with atrial fibrillation detector device and to compare its accuracy with Holter monitoring
To investigate the agreement in the detection of paroxysmal AF using simultaneously the 24h-ABP with AF detection device and loop recording
To observe at which level of TOD asymptomatic AF episodes are more commonly detected
To study if there is any relationship between systolic andor diastolic BP levels with AF occurrence
To examine whether office HR or mean HR using ABPM is associated with the development of silent AF episodes
To examine whether a wide PP in ABPM is associated with the development of silent AF episodes
Variables used to determine the primary and secondary endpoints
Sociodemographic data birth date gender education level employment status place of residence smoking statushabits alcohol consumption
Anthropometric characteristics body weight height waist circumference
Any abnormal findings on physical examination
Clinical relevant medical history and comorbidities
Concomitant medications
Electrocardiographic assessment
Investigation of TOD including echocardiography carotid artery triplex 24h-urine albumin excretion and ABI
Recent laboratory testing results including hemoglobin hematocrit blood glucose kidney and liver function tests
Management of HTN pharmacologic and non-pharmacologic treatment
Inclusion Criteria
Patients diagnosed with essential HTN office BP14090mmHg or patients receiving at least one antihypertensive medication ie RAAA inhibitors or diuretic aged 18-85 years of age
Patients with at least one of the following risk factors organ damage or other evidence of cardiovascular disease
Previous stroke
Transient ischemic attack TIA
Systemic embolism
Diabetes mellitus type 2
Obesity
Obstructive sleep apnea OSA
Dyslipidemia
History of coronary artery disease CAD
Valvular heart disease VHD
Echocardiographic findings attributed to HTN ie diastolic dysfunction LVH
White coat hypertension WCH masked hypertension MH
Positive family history for rhythm disturbances
Exclusion Criteria
Patients already diagnosed with paroxysmal or permanent AF
Severe renal insufficiency eGFR according to MDRD formula 25mlmin173m2
Patients unable to attend follow-up visits
Clinical evidence of severe heart failure
Suspected secondary HTN
Mental disorders
Patients with cancer
The study protocol needs to be approved by the scientific board of the hospital and signed informed consent needs to be obtained from all participants
Study Design We are going to conduct a cross-sectional observational study
Likewise hypertension HTN also constitutes a major public health problem globally and its prevalence is set to increase owing to widespread population ageing This epidemiological trend is especially prevalent in rapidly developing countries where early routine screening at any point of health care is underutilized among risk subjects due to several perceived barriers Moreover HTN awareness is critical for optimal BP control since under-diagnosis under-treatment andor un-treatment of high BP levels can have deleterious effects on the cardiovascular system In addition HTN is the single most important risk factor for cerebrovascular stroke and it has been clearly demonstrated that it is also associated with structural and functional changes in the myocardium that favor the development of AF further increasing the risk of thromboembolism Among those alterations left ventricular hypertrophy LVH impaired ventricular filling left atrial enlargement and slowing of atrial conduction velocity have been identified as important heralds of cardiovascular morbidity and mortality More specifically since HTN and AF are two conditions that often co-exist especially in patients with advanced age the risk for considerable morbidity and mortality is increased even more which points towards the significance that optimal BP control holds in the prevention of cardiovascular events To our knowledge in the Framingham Heart Study after controlling for age and other predisposing conditions HTN and diabetes emerged as the only cardiovascular risk factors predicting AF
It has also been suggested that nocturnal HTN and non-dipping of BP during sleep are distinct entities that often occur together and are regarded as important harbingers of poor cardiovascular prognosis Recently Pierdomenico et al showed that non-dipper sustained hypertensives have a two-fold greater risk of developing AF than dipper ones This may be due to the fact that nighttime HTN may be a powerful determinant of long-standing left ventricular diastolic dysfunction which subsequently increases atrial stretch Furthermore it has been observed that nighttime hemodynamics are associated with higher sympathetic and reduced vagal activity which may trigger AF Additionally sympathetic activation is associated with the stimulation of the renin-angiotensin-aldosterone axis RAAA which leads to increased left ventricular diastolic preload both atrial and ventricular fibrosis exerting thus direct cellular electrophysiological effects Besides scientists suggested that nighttime HTN is better associated with cardiovascular target organ damage TOD as compared with the non-dipping pattern
According to the most recent guidelines of the ESH the presence of microalbuminuria increased pulse wave velocity LVH on echocardiogram and carotid plaques detected during carotid ultrasonography constitute markers of asymptomatic organ damage and it has been clearly demonstrated from multiple studies that they can predict CV mortality independently of SCORE stratification
In our study we will try to investigate whether abnormalities in the circadian rhythm of BP such as extreme dipping or non-dipping pattern andor morning surge in hypertensive subjects with or without TOD are associated with the development of new-onset paroxysmal AF
24-hr ambulatory BP monitoring ABPM along with the 24-hour blood pressure monitors with AF detector will help us to examine the incidence of AF in extremely dippers or non-dippers andor patients exhibiting a morning surge in BP with or without TOD Some of the questions that we aim to answer while conducting this study are whether an asymptomatic AF episode is more commonly detected in extreme dippers non-dippers or morning surgers during daytime or during nighttime or whether TOD is associated with asymptomatic AF episodes
Importantly Iqbal et al demonstrated that there is an association between AF and nighttime DBP On top of that during the past decade a research study conducted in 546 hypertensive subjects aged 60 years of age and who were followed-up for 92 years showed that DBP whether 24-hr mean daytime mean or nighttime mean provided the most incremental value for the prediction of morbid events Thereby we want to examine if AF episodes have any association with the 24hr systolic and the diastolic blood pressure DBP levels It would also be interesting to observe for any associations between AF occurrence and the mean 24-hr ABPM and office heart rate HR
Moreover it has been showed that pulse pressure PP determines left atrial enlargement in non-dipper patients with never-treated essential HTN Thus in our study we will also examine whether a wide PP is associated with silent AF episodes in treated hypertensive subjects
Summarizing the goals of our study are to determine athe association between abnormal circadian BP and the development of paroxysmal AF in hypertensive patients bat which level of TOD paroxysmal AF episodes are detected in hypertensive subjects cif there is any association between systolic andor diastolic BP levels with AF occurrence dwhether the mean heart rate during a 24-hr interval is associated with the development of paroxysmal AF and finally eexamine the relationship between a wide PP and asymptomatic AF episodes in patients with HTN
Study Population We will evaluate all adult patients referred by their family physicians to the Hypertension and Cardiovascular Prevention Outpatient Clinic at Evangelismos General Hospital in Athens from June 2015 to present
All patients with an average office systolic BP 140 mmHg andor an average diastolic BP 90 mmHg on three consecutive visits are considered as having essential HTN Furthermore individuals under treatment with one or more antihypertensive drug are also enrolled in the study
Objectives Primary endpoint
To investigate whether nighttime BP patterns extreme dipping normal dipping or reduced dipping and non-dipping including risers or early morning surge are associated with the detection of paroxysmal AF in hypertensive subjects
Further definitions Normal diurnal systolic and diastolic BP pattern arterial BP has a daily variation characterized by substantial reductions during sleep a rapid rise upon awakening and increased variability during the awake period in ambulant normal subjects and hypertensive patients
Reduced diurnal systolic and diastolic BP pattern nocturnal systolic andor DBP fall from 1 to 10 of daytime values or nightday systolic andor diastolic BP ratio 1 and 09
Nocturnal HTN increased absolute level of night time systolic andor diastolic BP 12070 mmHg19 Dipping pattern is defined as daytime-nighttime BPdaytime BP reduction - based on either ABP or home BP HBP monitoring- greater than 10 for systolic andor diastolic BP Nighttime HTN is defined as nighttime ABP or HBP 12575 mmHg systolic andor diastolic
Non-dipping and rising no reduction or increase in nocturnal systolic andor diastolic BP or nightday systolic andor diastolic BP ratio 1
Extreme dipping marked nocturnal systolic andor diastolic BP fall20 of daytime systolic andor diastolic values or nightday systolic andor diastolic BP ratio 08
Morning surge excessive systolic andor diastolic BP elevation rising in the morning
Secondary endpoints
To detect asymptomatic and intermittent AF using a 24h ABPM with atrial fibrillation detector device and to compare its accuracy with Holter monitoring
To investigate the agreement in the detection of paroxysmal AF using simultaneously the 24h-ABP with AF detection device and loop recording
To observe at which level of TOD asymptomatic AF episodes are more commonly detected
To study if there is any relationship between systolic andor diastolic BP levels with AF occurrence
To examine whether office HR or mean HR using ABPM is associated with the development of silent AF episodes
To examine whether a wide PP in ABPM is associated with the development of silent AF episodes
Variables used to determine the primary and secondary endpoints
Sociodemographic data birth date gender education level employment status place of residence smoking statushabits alcohol consumption
Anthropometric characteristics body weight height waist circumference
Any abnormal findings on physical examination
Clinical relevant medical history and comorbidities
Concomitant medications
Electrocardiographic assessment
Investigation of TOD including echocardiography carotid artery triplex 24h-urine albumin excretion and ABI
Recent laboratory testing results including hemoglobin hematocrit blood glucose kidney and liver function tests
Management of HTN pharmacologic and non-pharmacologic treatment
Inclusion Criteria
Patients diagnosed with essential HTN office BP14090mmHg or patients receiving at least one antihypertensive medication ie RAAA inhibitors or diuretic aged 18-85 years of age
Patients with at least one of the following risk factors organ damage or other evidence of cardiovascular disease
Previous stroke
Transient ischemic attack TIA
Systemic embolism
Diabetes mellitus type 2
Obesity
Obstructive sleep apnea OSA
Dyslipidemia
History of coronary artery disease CAD
Valvular heart disease VHD
Echocardiographic findings attributed to HTN ie diastolic dysfunction LVH
White coat hypertension WCH masked hypertension MH
Positive family history for rhythm disturbances
Exclusion Criteria
Patients already diagnosed with paroxysmal or permanent AF
Severe renal insufficiency eGFR according to MDRD formula 25mlmin173m2
Patients unable to attend follow-up visits
Clinical evidence of severe heart failure
Suspected secondary HTN
Mental disorders
Patients with cancer
The study protocol needs to be approved by the scientific board of the hospital and signed informed consent needs to be obtained from all participants
Study Design We are going to conduct a cross-sectional observational study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None