New Understandings/ New Opportunities Learning Objectives Show why - PowerPoint PPT Presentation

Reassessing the Definition and Treatment of Severe Hypertension New Understandings/ New Opportunities

Learning Objectives Show why the current definitions of severe HTN are 1. wrong and suggest changes Provide a ‘working’ understanding of the 2. microcirculation 3. Briefly introduce old and newly acquired technologies for measuring the microcirculation Convince you that this is important to you as a 4. Cardiologist caring for the vascular health of your patients

ASSESSMENT OF SEVERE HYPERTENSION 1. How high is the BP (> 180/120 mmHg)? 2. Is there evidence of critical vascular damage in vital organs? AMI Pulmonary edema Hemorrhagic Stroke Hypertensive encephalopathy Dissecting aneurism Acute renal failure

PRES (RPLE) (Posterior Reversible Encephalopathy Syndrome) Cardinal Sx: H/A, altered LOC, seizures (generalized or focal, usually multiple including status epilepticus and can be non convulsive), focal neurological sx, particularly visual disturbances. PRES is 2- fold more common in females. Diagnosis: Clinical features + early Neuroimaging. Seen on MRI with T2 Diffusion weighted/FLAIR and DWI is the gold standard. The posterior circulation is almost always involved, but can include anterior circulation and brainstem. Also, do an EEG. ??? OCT-SD Prognosis: Potentially reversible with recognition and aggressive use of antihypertensive agents and anticonvulsants. However, can progress to ischemia/hemorrhage with permanent deficits and even death if not and treated promptly and appropriately.

MAP = 100 BERNOULLI’S PRINCIPLE (conservation of energy) P c = 25

AUTOREGULATION OF CEREBRAL BLOOD FLOW CBF 60 120 Mean Arterial Pressure (mmHg)

STARLING EQUATION (the convective movement of water and small solutes across membranes) P filtration = P transudation - P oncotic = (P cap - P interst ) - (O cap - O interst )

AReg  P/  R=±F  P P c ± F c ± NonReg P c  F c   P/ ± R=  F

AReg  P/  R=±F  F P c ± F c ± NonReg P c  F c  P c  F c   P/ ± R=  F

Re-setting of CEREBRAL AUTOREGULATION Time Course of this is Minutes, Up to an Hour CBF 60 120 Mean Arterial Pressure (mmHg)

AUTOREGULATION of a very abnormal Cerebral Circulation CBF 60 120 230 Mean Arterial Pressure (mmHg)

Systematic Review of All Cohort Studies and Case Reports of Hypertensive PRES 2005-2011 149 HTN MAP PRES MAP Baseline Median Delta MAP Delta MAP Mean 147 100 37 38 95% CI 143-150 93-106 31-45 205/118 (200-209/114-121) from an  baseline BP BP equiv

C+Tx C+Tx C+Tx CisP

Loss of AUTOREGULATION of Cerebral Blood Flow { 15mmHg } CBF 60 70 90 105 120 Mean Arterial Pressure (mmHg)

Reported Associations with PRES Hypertension, sudden and severe, or not severe but significantly elevated above baseline BP Eclampsia Immunosuppressive Rx (cyclosporine, tacrolimus/sirolimus, steroids) Cytotoxic agents (cyclophosphamide, cisplatin and Pl analogues) Acute or chronic renal failure Alpha interferon, IgG, antiretroviral Rx, VEGEF inhibitors (bevacizumab) Post Vaccination for measles Lupus and other CTD TTP/HUS Erythropoetin Blood transfusions Acute Intermittent Porphyria HIV Sepsis BM transplant Hypercalcemia/hyperparathyroidism Contrast agents Stimulant abuse

149 HTN MAP PRES MAP Baseline Delta MAP Median Delta MAP Mean 147 100 37 38 95% CI 143-150 93-106 31-45 BP Equiv 205/118 (200-209/114-121) from a (N) baseline BP 37 Low MAP PRES MAP Baseline Delta MAP Median Delta MAP BP Mean 98 94 3 2 95%CI 87-103 89-99 -8-14 BP Equiv 139/77 (131-146/73-82); baseline 5 mmHg lower

ASSESSMENT OF SEVERE HYPERTENSION 1. Is there evidence of critical organ damage? 2. Has there been a blood pressure elevation high enough and long enough to account for that organ injury? 3. What was the patient’s baseline BP in the days or weeks prior to the event? 4. Has the BP been poorly controlled for any length of time in the past?

TOD for Dx of a Hypertensive Emergency Supporting Evidence Major Criteria Hypertensive encephalopathy/PRES Proteinuria/microalbuminuria Acute stroke - ischemic or hemorrhagic Pressure natriuresis Acute coronary syndrome Elevated urate Acute LV dysfunction/pulmonary edema Thrombocytopenia Acute aortic dissection Schistocytosis Acute renal failure Elevated LDH Pregnancy + symptoms of PRES Coagulopathy Pregnancy + HELLP syndrome Fx impairment of any other organ Pregnancy + capillary leak (  BP not req’d) Significant troponin leak Intractable bleeding P max , PWD, repolarzn abn on ECG Syndromes of catecholamine excess

A Severe BP Rise Should be Defined: a) In all patients, as a persistent rise in MAP of greater than 30-45 mmHg over baseline MAP, or if baseline MAP is not known, above an MAP of 90 mmHg developing over the course of several hours to days, or a rise in MAP of 40- 60 mmHg lasting longer than 1 hour. b) In patients with sepsis/SIRS or those receiving immune modulating or cytotoxic chemotherapy that potentially impair cerebral autoregulation and/or vascular permiability, BP elevations less than these levels may similarly cause a hypertensive emergency.

c) Patients with poorly controlled hypertension with BPs above 180/120 for a period of time greater than 3 to 6 months are likely to possess adaptive structural changes in their heart and systemic vasculature that support a higher BP. These people are at particular risk of ischemic injury if the BP is rapidly lowered below autoregulatory limits. Thus, severe, poorly controlled hypertension is also a Hypertensive Emergency

Long Term Outcome of Patients After a Hypertensive Microvascular Event MacDonald et al. Am Heart J 2008; 156:91830 Meta-analysis of 5 case control and 10 cohort studies 116,175 eclamptics, 2,259, 576 controls, age < 56 yr OR of subsequent CVD including MI, stroke & CV mortality 2-fold. Also showed an increasing graded risk for  severity Bellamy et al. BMJ; doi:10.1136/bmj.39335.385301.BE Meta-analysis of all prospective and retrospective studies 198,252 eclamptics, 3,488,160 controls, weighted mean f/u 14.7 yr OR for IHD, stroke and VTE 1.8-2.2; overall mortality 1.5 Absolute risk of IHD was 4% at 11.7yrs

D E M E N T i A

How Can We Assess Whether the Microcirculation is in Trouble? EEG, MRI Microalbuminuria Pressure Natriuresis, Uric acid INR, VWF, platelet cts, schistocytosis, lactate P-wave dispersion, repolarization abns on the ECG, CMR Ach- or other endothelial-mediated vasomotion Studies of the retinal microvasculature OCT-SD

Hughes AD et al. J Hypertension 2006;24:889-94