Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Essential Hypotension and Allostasis Registry

Summary: The essential arterial hypotension and allostasis registry is a prospective, observational research that has the purpose of demonstrating that essential blood pressure (BP) disorders and the associated comorbidities are a result of the inappropriate allostatic response to daily life stress. This required a functioning brain orchestrating the evaluation of the threat and choosing the response, this is a mind-mediated phenomenon. If the response is excessive it contributes to high BP, if deficient to low BP, and the BP itself will identify the allostatic pattern, which in turn will play an important role in the development of the comorbidities.
  To do so, consecutive patients of any age and gender that visit a cardiologist's office in Medellin, Colombia, are recruited. Individuals are classified according to their arterial BP and allostasis and follow them in time to see what kind of diseases develops the most (including BP) in the follow up according to the categorization of the characteristic chosen and after adjustment for confounder's variables. In addition, stress events with their date are registered.
  HYPOTHESIS
  The causes of the diseases are multifactorial.
  Physical, biochemical, psychological, social, and cultural dimensions of development dynamically interact to shape the health development process.
  A person´s health depends on their:
  1. Biological and physiologic systems
  2. External and internal environment (a) physical, b) internal behavioural and arousal state as registered by the brain.
  3. Their interaction.
  The allostatic mechanisms to the internal and external stressors (allostatic load) involves a network composed by:
  1. Functional systems; mediated by:
  1. The Autonomic Nervous System
  2. The endocrine system
  3. The immune system
  2. Structural changes: whenever the internal and/or external stressors are long lasting and/or strength enough, they may induce changes in:
  1. Epigenetic, endophenotypes, polyphenism.
  2. Plasticity
  3. The interaction between a) and b).
  The network response do not affect exclusively the BP, propitiating the development of comorbidities, which may prompt strategies for prevention, recognition and ultimately, treatment.
  The allostatic model defines health as a state of responsiveness.
  The concept of psycho-biotype: The allostasis is the result of both: biological (allostasis) and psychological (psychostasis) abilities. It is proposed that both components behave in similar direction and magnitude.
  Immune disorders may be associated with the development of cancer. High BP population has a higher sympathetic and lower vagal tone, this has been associated with a decrease in the immune´s system function.
  Resources and energy depletion: Terms like weathering have been used to describe how exposures to different allostatic loads gradually scrape away at the protective coating that keeps people healthy. It is postulated that High BP individuals have more resources and energy.

Detailed description: DEFINITIONS
  ARTERIAL BLOOD PRESSURE CLASSIFICATION
  Arterial Blood Pressure (ABP) is a complex physiological variable in regard to its measure, behavior between BP taken in the same visit at the office and between these and ABPM, chronobiology (different day time BP levels), evolution in time, meaning and classification.
  Not appropriate approach or analysis may be addressed without taking into account all the BP characteristics that have demonstrated prognostic implications.
  In order to arrive to the most comprehensive analysis, BP classification takes into account the following characteristics:
  I. Cause of BP disorder
  A. Primary or Essential: Not clear causes may be identified. Multiple mechanisms may be involved, obvious players and contributors, but no definitive cause.
  B. Secondary: an identifiable cause is characterized.
  .
  II. The supine BP and/or ABPM value
  A. High arterial BP (HBP):
  1. At the office: the two systolic and diastolic supine BP are considered. a) Office Supine SBP ≥140 mm Hg and/ or DPB ≥90 mmHg b) Diagnosis HBP: any value is HBP, as single criteria in the abscence of ABPM
  2. Ambulatory BP Monitoring (ABPM):
  1. 24 hrs: SBP ≥130; DBP ≥80 mmHg.
  2. Awake (06:00-22:00): SBP ≥135; DBP ≥85 mmHg.
  3. Night (22:00-06:00): SBP ≥125; DBP ≥70 mmHg.
  3. Both at the office and ABPM always predominate ABPM:
  1. HBP in ABPM at 24 hrs, awake or night time, regardless of the office BP
  2. Masked hypertension (MHBP): HBP in the ABPM and NBP or LBP at the office.
  4. Normal BP at the office and/or at the ABPM in presence of anti hypertensive treatment.
  B. Low BP (LBP) Since there are no clear limits in ABPM for LBP, only office supine SBP and/or DBP will be considered.
  SBP <90 DBP <60
  C. Normal BP (NBP) > 90 SBP <140 > 60 DBP <90 Include patients with HBP at the office but normal ABPM, White Coat Hypertension (WCHBP)
  .
  III. The BP orthostatic response
  A. Orthostatic hypotension (OhypoT): Drop in BP upon standing
  -  20 mmHg if SBP is normal
  -  30 mmHg if SBP ≥140
  -  10 mmHg in DBP
  B. Orthostatic Hypertension (OhyperT) Rise in SBP upon standing ≥20 mmHg
  C. Orthostatic Normotension (ONT): No criteria for Ohypot or OhyperT .
  IV. The circadian component of BP
  A. Normal Dipper (NDBP): average decrease of SBP between day and night time greater than 10% and less than 20%
  B. Extreme Dippers (EDBP): greater than 20% fall
  C. Nondippers (NonDBP): less than 10% fall
  D. Reverse dippers (RDBP): night time BP higher than daytime average
  E. Abnormal early Morning BP Surge (BPS): A rise ≥50 mmHg.
  .
  V. BP response to treatment (requires office BP and ABPM)
  A. True Control HBP (TCHBP): NBP at the office and the ABPM
  B. True Resistant HBP (TRHBP): HBP at the office and the ABPM
  C. False Control HBP (FCHBP): NBP at the office and HBP in the ABPM
  D. False Resistant HBP (FRHBP): HBP at the office and NBP in the ABPM.
  Patients must be in the absence of medication for Essential hypotension diagnosis and hypotension must be dismissed as a secondary manifestation of another disease or other condition such as dehydration, medication causing hypotension for other conditions or secondary dysautonomia.
  There are 3 types of orthostatic hypotension Initial: in the first 30 sec. after assuming the standing position Classic: It occurs between the 1st and 3rd min. Late: It occurs between 5 and 45 min. later (no patients within this category)
  ESTIMATION OF TARGET-ORGAN DAMAGE Electrocardiogram, Doppler color 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. The treatment starts with a low-sodium diet (by nutritionist whenever possible), increase in fruits and vegetables intake, weight loss, aerobic exercise, stop smoking, and changes in lifestyle.
  The pharmacological first step is the use of IECAs (ARA II if there is cough), calcium channel blockers, 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 Beta blockers are chosen. Alpha blockers are the last step therapy.
  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 liters of water per day, do aerobic exercises, and raise the head of the bed. If there is not improvement, the patient can wear gradient tights up to the waist. Next step is start Fludrocortisone 0.05 daily or every other day. The last step is Midodrine (from 5 to 20mg daily, distributed at 06:00, 10:00 and 14:00 hrs or when needed, avoid it after 6:00 pm). Counterpressure maneuvers are recommended if there is a threat of syncope.
  ALLOSTASIS
  For the effects of what is mentioned here, allostasis is defined as the ability to maintain homeostasis through the neuroendocrine and immune 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 Allostasis:
  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 not syncope itself, it is called vasovagal component.
  3. BLOOD PRESSURE: Low BP
  The allostasis is classified as:
  1. Hypo-allostasis: 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-allostasis: 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 65 yo. After this age, structural components mainly in the Windkessel vessels, may contribute more than the increased sympathetic tone to the hypertension phenomenon. For end points analysis, patients developing Hypertension after 65 yo are considered hypertensives in their BP group, but normal in the adaptability.
  3. Hyper-allostasis: Arterial hypertension starting before 66 yo, with no identifiable cause, no symptoms of hypotension, no neurally mediated syncope or vasovagal syncope.
  Allostasis scores (scores between 1 and 7 apply for hypo-allostasis only)
  1. Only 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
  METHODS
  Cohort.
  LABORATORY EXAMINATIONS
  Complete blood count Basal glycemia and 2 hr post-load 75 g glucose Insulinaemia Glycated hemoglobin Serum ferritin Thyroid stimulating hormone and sometimes free thyroxine Sodium and serum potassium Uric acid Lipid profile Creatinine Basal serum cortisol and/or post-Adrenocorticotropic hormone 24-hr urinary free cortisol Post-dexamethasone cortisol: in those with high cortisol with not recognized cause Microalbuminuria Others depending on the case, such as: 24-hr urine catecholamines (Epinephrine, Norepinephrine and Metanephrines), gliadin antibodies, vanillylmandelic acid, parathyroid hormone, vitamin B12, folic acid, ANAs, testosterone, creatinine clearance, antibodies against human hemoglobin in stool, hypersensitive reactive C protein, 24-hrs 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. After May 2016 measurements are taken in the office.
  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 BP respectively.
  About 6 BP measurements are taken, two on supine position and the second one after 5 min. 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 once the up-right position is assumed (first 30 sec). Then, additional pressures are taken at the first, second and third min.
  Since November the 30th, 2017, two additional BPs will be taken in a seated position; these will be taken at the beginning of the BP taking session. The patient will be seated comfortably with their right arm resting at the heart level. The BPs, HRs, COs and SVRs will be taken first after one minute of having the patient sit comfortably and then again after two minutes. Later on, the patient will assume the first supine position and the protocol continues as explained previously; however, the interval between the two BPs taken at the supine position will be of one and three minutes.
  Starting on January 2018, an immediate standing BP after seated position will be taking.
  The same process is fulfilled for the HR, taken in 15 sec. 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 BP levels. The patient is asked to have an empty bladder and the Physician tries to support the patient´s arm at the heart level in every position.
  NON-INVASIVE BEAT TO BEAT BP MONITORING Non-invasive, beat to beat, BP monitoring and Cardiac Output (CO) and Systemic Vascular Resistance (SVR) started to be used since May 2017 to measure BP, HR, CO, SVR. CNAP Monitor 500, CNSystems, is CE and FDA approved. It is intended to be use in every consecutive patient.
  Instructions:
  1. Rings, bracelets, and wristwatches should be withdrawn from the right arm.
  2. Fingers in the cuffs should not be bending since this could increase BP artificially.
  3. The arm will rest beside the body, relaxed.
  4. When standing, the physician or person taking BP should take the patient´s right arm and help him stand up in an attempt to decrease the arm´s movement and avoid interference on the recording.
  5. The forearm is kept at the heart level.
  6. A screen´s photography will be taken with the cellphone after every BP measure (8).
  7. A label is placed on the recording just after the seating position and before standing.
  8. If the immediate standing BP taken shows a drop in the BP but systemic vascular resistance (SVR) and cardiac output (CO) are those of the supine position then the BP won´t be registered and a picture should be taken immediately SVR and CO are recalculated.
  9. If BP starts to rise, review that fingers in the cuff are straight.
  10. If in doubt, make a manual measure of the BP.
  11. BP and HR date along with SVR and CO will be introduced in the fields of the BP and HR taken with the sphygmomanometer and usual physical examination. New fields were created for SVR and CO.
  12. The completed data is introduced as 3 attachment files for further analysis.
  ELECTROCARDIOGRAM (HEWLETT PACKARD AND MORTARA) A careful reading of each plot is made in which the HR, PR and cQT intervals, and QRS complex are recorded (automatic measurements).
  24 HOURS ECG MONITORING (HOLTER) 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 hrs, 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 hrs, in the day and at night, as in the 24-hr 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 hrs 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 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.
  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.
  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 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/min; the sedation is obtained with Midazolam, administered 10 min. before starting the measurements.
  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 min, 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 min, it is evaluated the response of the HR to the infusion of 3 micrograms of Isoproterenol per min. (an increase of 25% from basal HR) and the intrinsic HR.
  This latter is made by administering Atropine 0.04 mg/kg and propranolol 0.2 mg/kg, the intrinsic HR 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.
  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 BP beat to beat monitor. (Task Force Monitor).
  The patient must be fasting for at least 4 hrs; should stay 5 min. in supine position and then is tilted at 60 degrees for 20 min. Then, it is administered 400 micrograms of sublingual nitroglycerin for 20 min. more. The tilt table test (TTT) is considered positive if the patient presents syncope or if the systolic blood pressure is lower than 60 mmHg. The hemodynamic variables, the HR variability, and the BP are written down for those patients who have these values available.
  Other diagnoses written down on the TTT 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 in diastolic BP ≥10 mmHg, at any time of the TTT.
  . Orthostatic Hypertension: rise in SBP ≥20 mmHg.
  -  Asystole: Isoelectric line that last for more than 3 sec. on the electrocardiogram plot. The duration in sec. 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 min, 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 TTT.
  CAROTID SINUS MASSAGE (CSM) It is made during the 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 sec. on each carotid sinus, allowing an interval of 1 min. between both sides. 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 last 3 or more sec. 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. 1. Computerized axial tomography of brain, heart 2. Brain or heart nuclear magnetic resonance 3. Polysomnography 4. Meta-iodo-benzyl-guanidine 5. Carotid, renal and lower limbs arterial Duplex 6. Heart or other structures biopsy 7. Others
  DATABASE We have over 1100 variables in OpenClinica 3.13
  UPDATING INFORMATION It is made through the consultations, phone calls or emails sent to the patient email address. The patients should be contacted annually if possible.
  Requested information:
  1. Updating of telephone number, cell phone number 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´s current weight and exercise
  6. Paraclinical laboratory tests.
  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, the diagnosis made by the psychiatrist always prevails.
  2. Panic attack:
  The diagnosis is made by a psychiatrist, the DSM IV criteria or both, the diagnosis made by the psychiatrist always prevails.
  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 min. of standing up, not associated with hypotension.
  5. Inappropriate sinus tachycardia:
  It is the HR average during the 24-hr 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 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 hrs in duration, and so it is considered in this protocol. Well-founded evidence suggests duration lower than 60 min, 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 min. 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 hrs A1C > 6.5.
  12. Cancer: It is diagnosed by an oncologist. It includes skin basal cell carcinoma.
  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 hrs.
  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 BP group 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 BP monitoring.
  To inquire what variables are different between the groups of BP. 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. 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.
  5. Black population is not represented in this sample.

Eligibility: 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 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

Relevance to patient case: not relevant