Essential Hypotension and Adaptability Registry (EssentialHAR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by CES University
Sponsor:
Information provided by (Responsible Party):
Luis Eduardo Medina, CES University
ClinicalTrials.gov Identifier:
NCT02018497
First received: November 29, 2013
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

The essential arterial hypotension and adaptability registry is an observational, prospective, cohort type, descriptive and comparative research about the low arterial blood pressure with no identifiable cause, in a population that visits a cardiologist's office in Medellin, Colombia.

The population consists of patients of any age and gender, which are classified according to their blood pressure in: normotensive, hypertensive and hypotensive. In addition, they are also classified according to their adaptability in hypo, normal adaptability and hyper.

The aim is to evaluate how clinical, laboratory, paraclinical examinations and certain comorbidities behave between the three groups of blood pressure and adaptability in order to define the meaning of the essential hypotension and the adaptability and propose possible mechanisms mediating this relationship.

HYPOTHESIS

This hypothesis is the result of previous exploratory studies that has been already published.

Causes of the diseases (Essential Hypotension) are multifactorial.

  1. The organism's ability to adapt to stress of any kind is vital for life. Type of stress that humans are exposed most often is the psychosocial stress.
  2. The organism´s response to stress involves the autonomic nervous, the endocrine and the inflammatory systems
  3. Stressor can be acute, sub-acute or chronic; isolated, simultaneous or repetitive; mild, moderate or severe, which will determine the total burden of stress.
  4. The organism has acute, sub-acute and chronic adaptation, and it has a limited reserve of response in each case.
  5. The individual's response to stress is not homogenous in the population, it may be: excessive, proportioned and deficient (Figure 1).
  6. Chronic stress requires resistance and resilience, which are also different between individuals (Figure 1). It is proposed that chronic stress is lower in hypotensive and higher in hypertensive (but the adaptability group could predominate over the blood pressure group).
  7. The adaptive response to chronic stress may contribute decisively to produce blood pressure essential disorders (Figure 2), high (excessive response) and low (deficient response).
  8. Essential disorders in blood pressure would be an indicator of the individual's adaptability to stress, and the associated diseases would be part of the same response spectrum.
  9. The physiological disorders or associated diseases to stress adaptability can be: a) the result of the adaptive response (for example, blood pressure essential disorders), or b) the lack of ability to adapt (for example, fibromyalgia and chronic fatigue syndrome) (Figure 1).
  10. It is considered that most of the individual's functions have their base in the Central Nervous System, which has a limited ability to fulfill these functions. If the reserve is low and the challenge too severe and prolonged, the Central nervous system would begin to relegate some functions and prioritize in others. Those relegated functions (such as pain control) may cause diseases such as fibromyalgia.
  11. The concept of essential: If the diseases afflicting an important mass of the population may be the result of the body's response to stress, in an attempt to maintain homeostasis, it is postulated that both the magnitude and direction of this response must have a distribution that is between one and two standard deviations of the Gaussian curve (see Figure 3), probably more or less than others.
  12. The concept of psychobiotype: The homeostasis (allostasis) is the result of both: biological (biostasis) and psychological (psychostasis) abilities. This concept propose that both components behave in similar direction and magnitude. For example, the hypotensive patients would fall their blood pressure by assuming the standing position (orthostatic stress), the blood glucose may fall within the first 2 hours of a 75 grams of glucose challenge (reactive hypoglycemia, metabolic challenge) (Figure 4) and they would have an increased susceptibility to stress (psychological stress), that may cause depression, among other pathologies. These responses would not be presented consistently in time.

Condition
Blood Pressure
Depression
Panic Attack
Fibromyalgia
POTS
Inappropriate Sinus Tachycardia
Coronary Heart Disease
Acute Coronary Syndrome (ACS)
Acute Myocardial Infarction (AMI)
Cerebrovascular Disease (CVD)
Transient Ischemic Attack (TIA)
Atrial Fibrillation
Diabetes Mellitus
Cancer
Systolic Heart Failure
Diastolic Heart Failure
Chronic Fatigue Syndrome
Syncope
Vasovagal Syncope

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 15 Years
Official Title: Essential Arterial Hypotension and Adaptability Registry

Resource links provided by NLM:


Further study details as provided by CES University:

Primary Outcome Measures:
  • Relationship between Blood pressure group and comorbidities [ Time Frame: A 7-year prospective study ] [ Designated as safety issue: No ]

    Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

    Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others.

    Cardiovascular mortality Total mortality


  • Relationship between adaptability group and comorbidities [ Time Frame: A 7-year prospective study ] [ Designated as safety issue: No ]

    Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others.

    Cardiovascular mortality Total mortality


  • Relationship between blood pressure group, adaptability group and comorbidities [ Time Frame: A 7-year prospective study ] [ Designated as safety issue: No ]

    Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

    Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others.

    Cardiovascular mortality Total mortality



Secondary Outcome Measures:
  • Relationship between blood pressure group, habits and anthropometric, metabolic, endocrine, Electrocardiogram, Holter, ambulatory blood pressure monitoring (ABPM) [ Time Frame: A 7-year prospective study ] [ Designated as safety issue: No ]

    Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

    Habits: smoke and drink

    Anthropometric variables: Body mass index, waist, hip

    Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, homoeostasis model assessment (HOMA), total cholesterol, LDL, HDL, triglycerides.

    Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone

    Electrocardiogram: HR; PR interval, QRS complex, cQT interval

    Holter variables: HR, standard deviation of NN intervals (SDNN) and sympathovagal balance, at day, night and 24 hs.

    ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.


  • Relationship between blood pressure group, adaptability group, habits anthropometric, metabolic, endocrine, electrocardiographic, Holter, ambulatory arterial blood pressure monitoring. [ Time Frame: A 7-year prospective study ] [ Designated as safety issue: No ]

    Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

    Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable.

    Habits: smoke and drink

    Anthropometric variables: Body mass index, waist, hip

    Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides.

    Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone

    Electrocardiogram: PR interval, QRS complex, Heart rate, cQT interval

    Holter variables: HR, SDNN and sympathovagal balance, at day, night and 24 hs.

    ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.


  • For metabolic disorders what it matters the most: the anthropometric variables vs blood pressure group vs adaptability group [ Time Frame: A 7-year prospective study ] [ Designated as safety issue: No ]

    Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

    Adaptability group: 1) Hyper adaptable, 2) normal adaptability and 3) hypo adaptable.

    Habits: smoke and drink, exercise

    Anthropometric variables: Body mass index, waist, hip

    Metabolic and other variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides; thyrotropine,

    Holter variables: HR, standard deviation of NN intervals (SDNN) and sympathovagal balance, at day, night and 24 hs.

    ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.


  • Relationship between adaptability group, habits and anthropometric, metabolic, endocrine, Electrocardiogram, Holter, ambulatory blood pressure monitoring (ABPM) [ Time Frame: A 7-year prospective study ] [ Designated as safety issue: No ]

    Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable.

    Habits: smoke and drink Anthropometric variables: Body mass index, waist, hip

    Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides.

    Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone

    Electrocardiogram: PR interval, QRS complex, Heart rate, cQT interval

    Holter variables: HR, SDNN and sympathovagal balance, at day, night and 24 hs.

    ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.



Other Outcome Measures:
  • Syncope Registry [ Time Frame: Up 100 weeks ] [ Designated as safety issue: No ]
    Clinical syncope characteristics (age of first syncope, number of syncope episodes, trauma, duration, clinical score, convulse, sphincter relaxation, etc.) Syncope cause Blood pressure group Adaptability group Prognosis

  • Tilt table testing (TTT) registry [ Time Frame: Up to 100 weeks ] [ Designated as safety issue: No ]

    TTT protocol: describe the protocol, the time at positive response, nitroglycerine use, autonomic and hemodynamic variables.

    TTT outcome for syncope: positive or negative TTT other outcomes: 1) Chronotropic incompetence, 2) arterial orthostatic hypotension, 3) carotid hypersensitivity, 4) POTS, 5) IST The relationship between TTT results and Clinical score for syncope in regard to: syncope behaviour and other orthostatic intolerance entities, symptoms and comorbidities.

    The relationship between neurally mediated syncope response at the TTT and comorbidities.


  • Sinus node function at the electrophysiological study (EPS) [ Time Frame: Up to 100 weeks ] [ Designated as safety issue: No ]
    EPS variables: AH, AV, CL, sino atrial conduction time (SACT), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), response to Isoproterenol, intrinsic heart rate Diagnosis: control, sick sinus syndrome, IST, chronotropic incompetence at the TTT HR at the ECG HR at the Holter monitoring HR at the TTT HRV at the Holter monitoring Syncope, cardiac or neurally mediated HR at the physical treadmill test Relationship with the blood pressure group Relationship with the adaptability group

  • Score for coronary artery disease [ Time Frame: Up to 200 weeks ] [ Designated as safety issue: No ]
    Define how the blood pressure group and/or the adaptability group may add to the already known and include in this registry, in the diagnosis of cardiovascular complications as coronary artery disease, cerebrovascular disease, peripheral artery disease, nephropathy.

  • Neurally Mediated Syncope: further of the transient lost of consciousness (TLC) [ Time Frame: A 7-year prospective study ] [ Designated as safety issue: No ]

    Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

    Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, COPD, and others.

    Mortality


  • Psychobiotype: relationship between biological and psychological variables [ Time Frame: Up to 100 weeks ] [ Designated as safety issue: No ]

    Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

    Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable.

    Psychiatric variables:

    1. Big Five Questionary (BFQ) for personality.
    2. Modify of the Coping Scale (Scale of modified coping strategies)
    3. Zung questionary for depression and anxiety
    4. MINI in those patients with moderate or severe depression and/or anxiety at the Zung questionary


Estimated Enrollment: 5000
Study Start Date: January 1995
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Consecutive patients who consult a cardiologist

Consecutive patients who consult a cardiologist - electrophysiologist since June 2006, regardless of the age or gender in the city of Medellin, Colombia. They could have consulted previously (considered as the enrollment date) if they had, at least, one measurement of their BP in supine position, and an immediate measurement of their BP in standing position that allows diagnosing their group of blood pressure. All patients have a record in paper and/or magnetic file and in OpenClinica.

No interventions.


  Hide Detailed Description

Detailed Description:

DEFINITIONS

ESSENTIAL ARTERIAL HYPERTENSION: without identifiable cause

  • In the doctor's office: one or more visits with Systolic Blood Pressure (SBP) numbers > 140 and Diastolic Blood Pressure (DBP) numbers > 90 mmHg.
  • Ambulatory blood pressure monitoring (ABPM):

Vigil: BP >135/85; Night: BP > 120/75; During 24 hours: BP > 130/80 (20,43,53)

  • Patients with old diagnosis who are under antihypertensive medication.

WHITE COAT HYPERTENSION: At least in one occasion; high blood pressure in the medical environment, and normal ABPM. They are assigned to the normal BP group.

MASKED HYPERTENSION: Blood pressure are in normal or in hypotension ranges during the consultations. The ABPM numbers are over the upper limit. They are assigned to the hypertension group

NORMOTENSION: All patients who are not included in the categories previously exposed, including those with white coat hypertension.

ESSENTIAL HYPOTENSION

SBP < 90 mmHg at any position. DBP < 60 mmHg at any position. A fall in systolic and/or diastolic blood pressure of 20 and 10 mmHg respectively, which occurs during the first 3 minutes after getting up.

Patients must be in the absence of medication for hypertension, and hypotension must be dismissed as a secondary manifestation of another disease or other condition such as: dehydration, medication causing hypotension for other conditions (like those used for prostatic hyperplasia and others) or secondary dysautonomia.

There are 3 types of orthostatic hypotension Initial: in the first 30 seconds after assuming the standing position. It represents the 78% of the population of this registry.

Classic: It occurs between the 1st and 3rd minute. Late: It occurs between 5 and 45 minutes later (no patients within this category.)

ESTIMATION OF TARGET-ORGAN DAMAGE Electrocardiogram, two-dimensional and/or Doppler echocardiogram, creatinine and urinalysis, lipid and metabolic profile and microalbuminuria are requested to the patients; carotid Doppler is also requested in patients with suspect of disorder.

ARTERIAL HYPERTENSION TREATMENT. Those with ambulatory blood pressure monitoring were treated if the numbers exceeded the normality levels, and prevail over the pressure levels obtained in the doctor's office.

The treatment always starts with a low-sodium diet (by the nutritionist), increase in fruits and vegetables intake, weight loss, exercise, stop smoking, and changes in the lifestyle (stress).

In patients without associate pathologies, the pharmacological first step is the use of Enalapril (ARA II if there is cough), as a second step the use of calcium channel blockers, and the third step is the use of diuretics like the Hydrochlorothiazide 12.5mg (or up to 25mg). If there is orthostatic hypotension, it is considered to start with Amlodipine. In those patients with tachyarrhythmia, heart failure or coronary disease is used Metoprolol or Carvedilol.

ESSENTIAL HYPOTENSION TREATMENT The treatment starts with the use of non-pharmacological measures consisting of postural hygiene (avoid assuming the standing position abruptly, avoid staying in the standing position for too long), eat salty (10 g), drink more than 2 or 3 liters of water per day, do aerobic exercises (for a routine, it is recommendable to start with 10 minutes of walking, cycling or swimming, four times a week), and raise the head of the bed. If there is not improvement, the patient can wear gradient tights up to the waist. If there is not improvement after complying with these measures, and if symptoms are significant, it is prescribed Fluorohydrocortisone 0.05 daily or every other day, making emphasis on the need of keeping the recommendations about water and sodium. Instructions are given about the need of keeping in touch due to the risks of hypertension or if there is a weight gain greater than 3 kg in the first month. Counterpressure maneuvers are recommended if there is a threat of syncope, it is recommended to sit or lie down on the bed to abort the syncope episode. Midodrine (from 5 to 20mg daily, distributed at 06:00, 10:00 and 14:00 hours or when needed, avoid it after 6:00 pm).

ADAPTABILITY

For the effects of what is mentioned here, adaptability is defined as the ability to maintain homeostasis through the neuroendocrine response to the stress of any type. There is experimental evidence, measuring the sympathetic nerve activity during the mathematical stress with microneurography of the peroneal nerve (muscle sympathetic nerve activity or MSNA) that the response may be increasing, neutral or decreasing.

The alterations in blood pressure are considered objective, which may be the result of strategies and different responses to stress (adaptability), through the neuroendocrine system (mainly the sympathetic nervous system).

The following variables are evaluated to describe the adaptability:

  1. SYMPTOMS OF HYPOTENSION: postural dizziness, dizziness after squatting, dizziness during childhood or adolescence (in elementary school, high school and occasionally in college) during the mass, at public events, religious processions or military parades. It is also taken into account the previous diagnosis of low pressure or "hypoglycemia" (which in our culture mainly refers to symptoms of orthostatic hypotension).
  2. HISTORY OF NEURALLY MEDIATED SYNCOPE OR VASOVAGAL SYNCOPE diagnosed by the scores of Calgary or Tilt-test; or vasovagal syncope (syncope caused by seeing blood, a venipuncture or donating blood; pain, by seeing or speaking about dramatic things, when coughing, swallowing, defecating, urinating, laughing, or other situations. If these situations occur with significant dizziness or pre-syncope, but it is not syncope itself, it is called vasovagal component.
  3. BLOOD PRESSURE

The adaptability is classified as

  1. Hypo-adaptability: presence of at least one of the followings:

    1. Symptoms of hypotension and/or
    2. Neurally mediated syncope (clinical or at the tilt-test) or vasovagal syncope and/or
    3. Hypotension at the office or at the tilt-test
  2. Normal-adaptability: normal blood pressure and no symptoms of hypotension, no neurally mediated syncope or vasovagal syncope (spontaneous or induced in the tilt table test) and no presence of hypotension. Include those who develop permanent hypertension after 70 yo.
  3. Hyper-adaptability: Arterial hypertension starting before 71 yo, with no identifiable cause, no symptoms of hypotension, neurally mediated syncope or vasovagal syncope.

Adaptability scores (scores between 1 and 7 apply for hypo-adaptive only)

  1. Only the presence of symptoms
  2. Only essential hypotension
  3. Only neurally mediated syncope
  4. 1 and 2
  5. 1 and 3
  6. 2 and 3
  7. 1, 2 and 3
  8. Normotensive
  9. Hypertensive
  10. The patient does not remember

Thus then, 3 groups of blood pressure are recognized at the moment of evaluating their impact on the comorbidities:

  1. Normotensive
  2. Hypotensive
  3. Hypertensive, that in turn can be:

    1. Hypertensive since the admission
    2. Previously hypotensive
    3. Previously normotensive

Here the evidence shows that there are individuals with essential hypertension and are hypo-adaptive. How can we reconcile this? Possible explanations are:

1. Other factors related to the elevation of blood pressure may be involved (greater genetic load, more structural changes, greater contribution of the renin-angiotensin-aldosterone system, etc.) 2. A change in the neuroendocrine response pattern by altering central regulators may be altered 3. Factors associated with age, but more active in this group of patients 4. It must be investigated about other causes of hypertension.

METHODS

Cohort.

LABORATORY EXAMINATIONS Complete blood count Basal glycemia and 2 hour post-load 75 g glucose Insulinaemia Glycated hemoglobin Serum ferritin Thyroid stimulating hormone (TSH) and sometimes free thyroxine (T4) Sodium and serum potassium Uric acid Lipid profile Creatinine Basal serum cortisol and/or post-Adrenocorticotropic hormone (ACTH) 24-hour urinary free cortisol Post-dexamethasone cortisol: in those with high cortisol with not recognized cause 24-hour urine catecholamines (Epinephrine, Norepinephrine and Metanephrines) Microalbuminuria Others depending on the case, such as: gliadin antibodies, vanillylmandelic acid, PTH (parathyroid hormone), vitamin B12, folic acid, ANAs, testosterone, creatinine clearance, antibodies against human hemoglobin in stool, hypersensitive reactive C protein (RCP), 24-hours urinary sodium, brain natriuretic peptide, etc.

There is not a single laboratory to make the blood tests, so there are different values of normality for some tests.

PHYSICAL EXAMINATION

ANTHROPOMETRIC MEASUREMENTS:

In every medical consultation, the patient is weighed wearing trousers or skirt. The waist is measured at an equidistant level between the last rib and the iliac crest. The hip is measured at the level of the greater trochanter. Finally, the size that appears in the identity card of the patient, or the latest measurement is written down.

TAKING OF BLOOD PRESSURE:

It is performed using a mercury sphygmomanometer from Tycos brand (it is revised annually in accordance with the current rules of the Ministry of Health), and it is controlled that the mercury column falls to 2 mm per second.

The bracelet must cover approximately the 80% of the forearm. We have three sizes of bracelets as needed, including a pediatric bracelet. This should be positioned at heart level.

The appearance of the first sound and the disappearance of Korotkoff sounds are taken as systolic and diastolic blood pressure respectively.

About 6 BP measurements are taken, two on supine position and the second one after 5 minutes supine, this second supine value is the one used to calculate the BP drop upon standing. Later, and having the bracelet previously inflated, the BP is taken immediately the supine position is assumed (first 30 seconds). Then, additional pressures are taken at the first, second and third minute.

The same process is fulfilled for the HR. During the taking of blood pressure neither the patient nor the doctor talk, and it is avoided making any comments that might alter the patient psychologically, and potentially modify their blood pressure levels.

ELECTROCARDIOGRAM (HEWLETT PACKARD AND MORTARA) It is made a careful reading of each plot, in which are recorded the HR, PR and cQT intervals, and QRS complex (automatic measurements).

24 HOURS ECG MONITORING (HOLTER) With at least 18 hours of registration, it is specified the patient rhythm, if is under medication that may affect the heart rate variability (HRV) and, it is recorded the name and type of drug. The number of supraventricular and ventricular premature complexes are counted.

The components of heart rate variability (HRV) allows calculating the sympathovagal balance (SVB) in 24 hours, in the day (06:00 to 22:00) and at night (22:00 to 6:00).

Low frequency (LF), high frequency (HF), very low frequency (VLF), Total power (TP) LF or HF one = LF or HF x 100/ TP-VLF SVB = LFone/HFone

AMBULATORY BLOOD PRESSURE MONITORING (ABPM) The systolic and diastolic BP and HR are registered in 24 hours, in the day and at night, as in the 24-hour Holter monitoring. This test is requested for all patients in order to define the presence of white coat hypertension or masked hypertension and to define an effective treatment.

Morning surge in SBP: It results from the difference between the averages of SBP taken in the first 2 hours from awakening and the lower nighttime.

COLOR DOPPLER ECHOCARDIOGRAM AND/OR STRESS ECHOCARDIOGRAM It is made the measurement of the heart and if the response to stress is positive or negative.

The ejection fraction (EF) is usually measured by the technique of Simpson or in a qualitative way.

Body surface area = (weight x height / 36) X 1/2 Cardiac mass = 1.05 [(LVDD + SW + PW)3 - LVDD3] - 14 Cardiac mass index = cardiac mass / body surface area

ABDOMINAL ULTRASOUND It is recorded the presence of fatty liver and abdominal aortic aneurysm

UPPER GASTROINTESTINAL ENDOSCOPY AND COLONOSCOPY The main findings are recorded

CORONARY ANGIOGRAPHY According to the judgment of the specialist who makes the examination, it is made a ventriculography and a qualitative or quantitative measurement of the EF.

Indication: For those who belong to the protocol and will indicate it, it is tried that the indication belongs to a score between 7 and 9 (appropriate test for a specific indication) of the recommendation of the working group aforementioned.

Indication:

  1. In patients with symptoms of acute coronary syndrome or positive test for myocardial ischemia in individuals with moderate or high cardiovascular risk
  2. In patients with sustained ventricular tachyarrhythmias with unidentifiable cause that stop spontaneously or require resuscitation
  3. In patients with left ventricular dysfunction at basal conditions (ejection fraction < 40%) and evidence of viability in the affected segments.
  4. Evidence of new segmental alteration of motility of unknown etiology, mainly if associated with symptoms of coronary disease.
  5. Suspected ischemic mitral regurgitation or interventricular septal defect.
  6. Presence on the CT scan of lesions > 50% on the left main trunk or other vessels, or possibly obstructive lesions of debatable severity in symptomatic patients (when in the left main trunk, also in asymptomatic patients)

It is classified according to the obstruction to coronary flow as follows:

  • Lesion < 50%, non-obstructive (if not the left main trunk)
  • Between 50 - 69%, intermediate lesion (if not the left main trunk)
  • > 70% or > 50% of the left main trunk, it is a significant obstructive lesion. It is neither specified the number of affected vessels nor the vessel diameter.

ELECTROPHYSIOLOGICAL STUDY The patient must be in a fasting state and must stop taking medications that affect the study for at least 5 half-lives. It is made by puncturing the right femoral vein, electro-catheters are placed in the high right atrium, in the bundle of His and in the right ventricular apex. It is stimulated the double of the thresholds to 3 cycle lengths (600, 500 and 430 ms) and three extra cycles, starting at 350 ms, and with successive decreases of 10 ms until the refractory period is found.

The study is made at basal conditions and in presence of Isoproterenol up to 4 micrograms/minute; the sedation is obtained with Midazolam, administered 10 minutes before starting the procedure.

Sinus function tests: Sinoatrial conduction time (by Narula method), the sinus node recovery time (SNRT) and the corrected sinus node recovery time (CSNRT)). For the SNRT, it is stimulated to several cycle lengths for one minute, with decreases of 100 ms up to 430 ms, and the longest pause is considered as the recovery time; if greater than 1500 ms is considered abnormal.

The CSNRT is the result of SNRT minus the cycle length of the patient. It is considered abnormal 500 ms or more (sensitivity of 85% and specificity of 90%). Additionally, at five minutes, it is evaluated the response of the heart rate to the infusion of 3 micrograms of Isoproterenol per minute (an increase of 25% from basal HR) and the intrinsic heart rate.

This latter is made by administering Atropine 0.04 mg/kg and propranolol 0.2 mg/kg, the intrinsic heart rate is dependent on the age, and is calculated as follows:

118.1 - (0.57 x age), for people under the age of 45 the value is adjusted + 14% and for people over the age of 45 + 18%.

Indication:

  1. In patients with syncope and ischemic heart disease, when the initial evaluation suggests an arrhythmic cause, except when it was already defined to implant an implantable cardioverter-defibrillator (ICD).
  2. In patients with syncope and bundle branch block, when the noninvasive evaluation has not clarified the diagnosis.
  3. When brief and sudden palpitations precede syncope, when the noninvasive evaluation has not clarified the diagnosis.
  4. In some cases of Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy.
  5. In high-risk patients in whom other methods have not clarified the diagnosis.

TILT TABLE TEST The patient is connected to the noninvasive blood pressure beat to beat monitor. Currently a Task Force Monitor is used.

The patient must be fasting for at least 4 hours; should stay 5 minutes in supine position and then is bent at 60 degrees for 20 minutes. Then, it is administered 400 micrograms of sublingual nitroglycerin for 20 more minutes. The tilt table test is considered positive if the patient presents syncope or if the systolic blood pressure is lower than 60 mmHg. The hemodynamic variables, the heart rate variability, and the blood pressure are written down for those patients who have these values available.

Other diagnoses written down on the tilt table test are:

  • Postural orthostatic tachycardia syndrome (POTS):
  • Inappropriate sinus tachycardia (IST):

It is defined as a HR greater than 90 bpm in supine position. - Orthostatic hypotension (OH): Fall in the systolic BP > 20 mmHg or a systolic BP lower than 90 mmHg, at any time of the Tilt Table Test. It can be symptomatic or asymptomatic.

- Asystole: Isoelectric line that last for more than 3 seconds on the electrocardiogram plot. The duration in seconds of the asystole is recorded.

  • Chronotropic incompetence (CI):

It refers to the inability of the heart to increase the HR more than 10% when standing up within the first 10 minutes, and if the HR in supine < 70 bpm. Also, if this criterion is not met but the HR to 60 degrees is lower than 65 bpm.

Indication:

Single syncope episode of unknown origin in high risk patients, or recurrent syncope in absence of organic heart disease; or in presence of organic heart disease if cardiac etiology was previously dismissed.

To show to the patient that he/she has this mechanism of syncope. To discriminate between reflex and orthostatic syncope To differentiate syncope from epilepsy To diagnose patients with recurrent unexpected falls To evaluate patients with recurrent syncope and psychiatric disease Many patients referred by other colleagues already have the Tilt-test.

CAROTID SINUS MASSAGE (CSM) It is made during the tilt table test (TTT)

Contraindications for the accomplishment of the procedure:

  1. History of cerebrovascular disease
  2. Acute myocardial infarction in the previous 3 months, or
  3. Presence of carotid bruit during the neck auscultation. The test consists of doing pressure and circular movements during 10 seconds on each carotid sinus, allowing an interval of 1 minute between both sides to avoid the additive effect of these two. The massage is made at 0 and 60 degrees tilt. It is considered a vasodilatory response if the systolic BP falls at least 50 mmHg, and chronotropic response if an asystole is induced for 3 or more seconds. If this latter occurs, it is expected the patient to recover and the carotid massage is repeated after applying atropine 1 mg. If still positive for syncope it is considered a mixed response to the CSM.

OTHER EXAMINATIONS

These tests are requested as needed to clarify other findings. Some of the diagnostic aids used are:

  1. Computerized axial tomography of brain, heart
  2. Brain or heart nuclear magnetic resonance
  3. Polysomnography
  4. Meta-iodo-benzyl-guanidine
  5. Extracranial circulation
  6. Renal and lower limbs arteries Duplex
  7. Heart or other structures biopsy
  8. Others

DATABASE We have over 1100 variables in OpenClinica 3.1.4

UPDATING INFORMATION It is made through the consultations, phone calls or emails sent to the patient email address. The patients should be contacted annually.

Requested information:

  1. Updating of landlines, cell phones and e-mail addresses
  2. Full treatment
  3. Patient is questioned about new family histories
  4. Patient is questioned about new comorbidities, when were they diagnosed and by whom, following the existing comorbidities in the database.
  5. Patient is questioned about his/her current weight
  6. Paraclinical laboratory tests are requested to the patient to write them down in the medical history.

COMORBIDITIES DIAGNOSTIC CRITERIA

  1. Depression:

    The diagnosis is made by a psychiatrist and/or if the patient meets the criteria of DSM IV. If there is difference between the psychiatric diagnosis and the DSM IV criteria, it always prevails the diagnosis made by the psychiatrist.

  2. Panic attack:

    The diagnosis is made by a psychiatrist, the DSM IV criteria or both, it always prevails the diagnosis made by the psychiatrist.

  3. Fibromyalgia:

    It is diagnosed by a rheumatologist.

  4. Postural Orthostatic Tachycardia Syndrome (POTS):

    • Increase in the HR > 30 bpm when standing up.
    • Increase in the HR > 40 bpm when standing up, between 12 and 18 years old.
    • HR > 120 bpm during the first 10 minutes of standing up, not associated with hypotension.
  5. Inappropriate sinus tachycardia:

    It is the HR average during the 24-hour Holter monitoring > 90 bpm, in absence of medication or hyperthyroidism.

  6. Coronary heart disease:

    It is diagnosed by the ACS criteria or by the abnormal coronary angiogram.

  7. Acute coronary syndrome (ACS):

    It refers to clinical, enzymatic, electrocardiographic, echocardiographic or angiographic findings, diagnosis of acute coronary disease. It should be dismissed the cocaine abuse, Prinzmetal's angina and Takotsubo cardiomyopathy. This latter is classified as such in a separate box.

  8. Acute myocardial infarction (AMI):

    Term used when there is evidence of myocardial tissue necrosis in the clinical spectrum of myocardial ischemia.

    Ischemic symptoms. New changes or presumed new in the ST segment and T wave, or a new left bundle branch block (LBBB).

    Development of new Q waves on the ECG Evidence by images of loss of viable myocardium, or the emergence of a segmental defect in the motility.

    Identification of an intracoronary thrombus in an angiography or autopsy.

    Criteria for prior myocardial infarction:

    Pathological Q waves on the ECG, with or without symptoms, in absence of non-ischemic causes.

    Evidence by images of loss of viable myocardium, which is thinner and does not contract, in absence of non-ischemic cause.

    Pathological findings of a previous MI.

  9. Cerebrovascular disease (CVD) or transient cerebral ischemia (TCI):

    The TCI has traditionally been considered as a deficit lower than 24 hours in duration, and so it is considered in this protocol. Well-founded evidence suggests duration lower than 60 minutes, and no evidence of nerve damage proved by CT scan or MRI.

  10. Atrial fibrillation:

    Baseline low amplitude oscillations with irregular rhythm, with major episodes of 6 minutes on the ECG, in presence or absence of symptoms, or associated with CHADS score >= 1.

    Any evidence of clinical relevance.

  11. Diabetes mellitus:

    Fasting glucose > 126 mgs/dl Occasional glucose > 200 mgs/dl with symptoms Glucose load (75 g): > 200 at 2 hours A1C > 6.5.

  12. Cancer:

    It is diagnosed by oncologist. It includes basal cell carcinoma (BCC).

  13. Systolic or diastolic heart failure:

    Patients should be symptomatic. It is considered systolic if the ejection fraction is decreased, otherwise, it is considered diastolic. In case of being diastolic, it should be dismissed other causes of dyspnea, such as lung diseases. If the origin is cardiac, it must be present with increased brain natriuretic peptide, which is requested.

  14. Chronic fatigue syndrome or idiopathic chronic fatigue:

    Persistent or chronic fatigue, clinically evaluated, unexplained, which lasts for 6 or more consecutive months, of recent onset, not explained by exercising, not improved substantially with rest and that produces a substantial reduction in previous levels of occupational, social, educational and personal activities.

    The patient must have 4 of the following symptoms, which must have persisted or be recurrent for 6 or more consecutive months of illness, and must have not been preceded by fatigue: a) self-reporting of poor short-term memory or decreased ability to concentrate, as severe as to alter the previous functional ability, b) dry throat, c) armpit and cervical adenopathies, d) muscle pain, joint pain without redness, deformity or swelling, de-novo headache, e) unrefreshing sleep, and malaise post exercise that lasts more than 24 hours.

    Some individuals have fatigue for more than 6 months but they do not meet the criteria previously set out. For example, they have major depression (other less intense depressions do not exclude the diagnosis), so they better qualify for idiopathic chronic fatigue.

  15. Syncope:

    It refers to the transient loss of consciousness secondary to cerebral hypoperfusion, characterized by sudden onset, short duration, and spontaneous and complete recovery.

  16. Vasovagal syncope Emotion mediated syncope or orthostatic stress, usually preceded by autonomic activation prodromes (diaphoresis, pallor, nausea). It includes situational syncope and carotid sinus hypersensitivity.

PSYCHO BIOTYPE EVALUATION

Design to study in depth the Psycho Biotype hypothesis. It consist of consecutive patients of each BP group to whom the following test are apply:

  1. Big Five Questionary (BFQ) for personality.
  2. Modified Coping Scale (Scale of modified coping strategies)
  3. Zung questionary for depression and anxiety
  4. MINI in those patients with moderate or severe depression and/or anxiety at the Zung questionary, apply by a psychiatrist

GENERAL OBJECTIVE

To demonstrate if the essential arterial hypotension and/or the adaptability are clinically important and try to identify the mechanism involve.

SPECIFIC OBJECTIVES

To demonstrate that the three groups of blood pressure differ in the numbers taken as much in the doctor's office as in the ambulatory blood pressure monitoring.

To inquire what variables are different between the groups of blood pressure. To inquire which comorbidities are more associated with each group of blood pressure and evaluate whether the differences persist after a multivariate analysis. The same will be done with the adaptability groups.

To provide hypotheses or evidences to explain the findings of the study.

DESIGN OF THE STUDY

This is an observational, analytic, cohort type study that aims to compare the differences between groups of patients classified according to their BP numbers and their adaptability.

To this end, variables of the clinical, paraclinical, imaging and comorbidities profile will be evaluated.

The database is designed to be flexible. It allows choosing different conditions in different variables. The diagnoses have 3 options: No, New and Old. It is recorded the date of the physical examinations, the diagnoses and the paraclinical results to ensure accuracy in the calculation of the age and the relationship between the different variables during the analysis.

The reports will be of prevalence (cross-sectional) and incidence (cohort). To evaluate the significance between the groups of blood pressure depending on morbidities and other variables, it is used a generalized linear model by adjusting the effect of the response variable based on the age, gender and tension group in all cases. In some cases, and when the response variable requires it, it is added the body mass index (BMI). When the response variable is qualitative, it is used a logit link function and it is obtained the corresponding Odds ratio with confidence intervals to 95%; while if the variable is quantitative it is used the identity function. Finally, the multiple comparison test of Tukey-Kramer is made in order to compare the groups of tension with a significance level of 0.05.

To evaluate the relationship between the blood pressure groups and the comorbidities, and other variables, the free events survival rates among participants using a Kaplan Meir survival curves, adjusted for age and other related variables.

For the diagnosis of coronary disease, it was used a generalized linear model in which was evaluated the adjustment of the effect in the groups of tension by age, gender, and body mass index (BMI), diabetes mellitus (DM), systolic and diastolic blood pressure in supine, total cholesterol, HDL cholesterol, smoking, and blood pressure group. Variables were selected by the method of Backward maintaining in the model those variables with a significance level of 0.05.

LIMITATIONS:

  1. Because patients were recruited at the doctor's office, some of them may decide not to take the required tests or decide not to come back.
  2. Some insurance companies may not provide some test, like the Ambulatory blood pressure monitoring.
  3. Also, the attending practitioner may be busy with too much work and has not available time to see the patients opportunely.
  4. The blood tests can be done at different sites and by different operators.
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Consecutive patients that visits a cardiologist's office in Medellin, Colombia. The population consists of patients of any age and gender, which are classified according to their blood pressure in: normotensive, hypertensive and hypotensive, they are also classified according to their adaptability in hypo, normo and hyper.

Criteria

Inclusion Criteria:

  • Any patient regardless of the age of gender

Exclusion Criteria:

  • Any non-correctable secondary cause of increase or decrease in blood pressure
  • or a pathology that alters the prognosis before the entrance of the patient into this registry.
  • nephropathy prior to the admission,
  • familial dyslipidemia,
  • previous gastric bypass,
  • pre-existing heart failure,
  • chemotherapy-induced cardiotoxicity,
  • arrhythmogenic right ventricular dysplasia,
  • long QT syndrome,
  • hypertrophic cardiomyopathy
  • restrictive cardiomyopathy or sudden death syndromes other than coronary disease
  • Down syndrome,
  • having one single kidney before entering to this registry,
  • polycystic kidney,
  • disability to continue with the treatment
  • organ transplantation (other than cornea),
  • HIV positive,
  • homocystinuria,
  • myelomeningocele,
  • autoimmune diseases,
  • paraplegia,
  • chronic infections (TB),
  • myocarditis of any cause,
  • blood dyscrasia with coagulation disorders,
  • history of pulmonary embolism,
  • sustained or non-sustained ventricular tachycardia,
  • idiopathic tachycardia associated with syncope or complex which is not cured by radiofrequency ablation,
  • pulmonary hypertension,
  • diabetes insipidus,
  • COPD,
  • Gitelman syndrome,
  • Cervical cancer associated with human Papillomavirus,
  • multiple sclerosis,
  • hemochromatosis,
  • not compact ventricle.

It is important to emphasize that all of these patients, currently excluded from the registry, may be studied in the future, they keep on follow-up and taken 6 BP.

Additionally it is planned to compare the evolution of patients with secondary causes of hypertension or hypotension with essential disorders

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02018497

Contacts
Contact: Luis Eduardo Medina, MD. (574)2323218 essentialhypotension@gmail.com

Locations
Colombia
CES University Recruiting
Medellín, Antioquia, Colombia, 00
Contact: Luis E Medina, MD    (57)3104055903    essentialhypotension@gmail.com   
Sub-Investigator: Jose F Florez, PhD         
Sub-Investigator: Jose M Cotes, PhD         
Sponsors and Collaborators
CES University
Investigators
Principal Investigator: Luis Eduardo Medina, MD. Researcher
  More Information

Additional Information:
Publications:
Medina E, Uribe W, Duque M, Alzate L. Variation of arterial blood pressure and heart rate during follow up in patients with orthostatic intolerance. XIth International symposium on the autonomic nervous system, Puerto Rico, 24-30 October 2000. Summary.
Medina E, Uribe W, Duque M, Alzate L. Severity of Compromise and level of Limitation in patients with Orthostatic Intolerance. XIth International Symposium on the autonomic nervous system, Puerto Rico, 24-30 October 2000. Summary
Medina LE, Ospina J, Lemos MA, Cuartas G, Calle J, Gutierrez M, Torres Y. Essential hypotension registry: Psychometric measurements for anxiety, depression and coping strategies: Hypotension is associated with depression and anxiety. Is there a psycho-biotype? Preliminary Report. Clinical Autonomic Research. Vol 19, number 5, page 296, 2009. Summary
Medina LE, Uribe W, Marin J, Aristizabal J, Velasquez J, Miranda A, Torres Y, Restrepo MA, Duque M. The importance of essential hypotension in syncope. A report of 877 patients. The essential hypotension registry. Clinical. Autonomic Research. Vol 20, number 2, page 140, 2010. Summary
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007 Jun;25(6):1105-87. No abstract available. Erratum in: J Hypertens. 2007 Aug;25(8):1749.
White W, Shah H. Ambulatory blood pressure monitoring in clinical hypertension management. In: Hypertension. A Companion to Branwald Heart Disease, 2013, Second edition, Chapter 6, Page 59. Edited by Black H and Elliot W.
Patel MR, Bailey SR, Bonow RO, Chambers CE, Chan PS, Dehmer GJ, Kirtane AJ, Wann LS, Ward RP. ACCF/SCAI/AATS/AHA/ASE/ASNC/HFSA/HRS/SCCM/SCCT/SCMR/STS 2012 appropriate use criteria for diagnostic catheterization: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, Society for Cardiovascular Angiography and Interventions, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012 May 29;59(22):1995-2027. doi: 10.1016/j.jacc.2012.03.003. Epub 2012 May 9.

Responsible Party: Luis Eduardo Medina, Researcher, CES University
ClinicalTrials.gov Identifier: NCT02018497     History of Changes
Other Study ID Numbers: LEMD001
Study First Received: November 29, 2013
Last Updated: May 23, 2014
Health Authority: Colombia: instituto nacional de vigilancia de medicamentos y alimentos INVIMA

Keywords provided by CES University:
Essential arterial hypotension
Arterial hypotension
Low blood pressure
Hypotension
Essential arterial hypertension
Syncope
Dysautonomia
Stress
Adaptability
Reactivity
Homeostasis
Allostasis
Allostatic load
Distress

Additional relevant MeSH terms:
Acute Coronary Syndrome
Atrial Fibrillation
Cerebrovascular Disorders
Coronary Artery Disease
Coronary Disease
Depression
Diabetes Mellitus
Fatigue Syndrome, Chronic
Fibromyalgia
Heart Diseases
Heart Failure
Heart Failure, Diastolic
Heart Failure, Systolic
Hypotension
Infarction
Ischemic Attack, Transient
Myocardial Infarction
Myocardial Ischemia
Myofascial Pain Syndromes
Syncope
Syncope, Vasovagal
Syndrome
Tachycardia
Tachycardia, Sinus
Angina Pectoris
Arrhythmias, Cardiac
Arterial Occlusive Diseases
Arteriosclerosis
Autonomic Nervous System Diseases
Behavioral Symptoms

ClinicalTrials.gov processed this record on October 20, 2014