Cerebrovascular Disease: A Discussion of Strokes and TIA’s

Cerebrovascular Disease: A Discussion of Strokes and TIA’s
Nebraska Home Office Life Underwriters Association Meeting Cerebrovascular Disease: A Discussion of Strokes and TIA’s Accompanied by an explanation of current use of IMT and Carotid Ultrasound Reviewed by Bill Rooney MD VP/Medical Director SCOR Global Life USA Reinsurance Company

These are intended to be interesting as well as thought provoking
Overview I have inserted some life-related quotes at the bottom of some of the slides Stroke Facts Mortality numbers Definitions Anatomy review Types of strokes Diagnosis Primary and secondary treatment Another look at Mortality numbers CIMT, Carotid US, and Silent strokes These are intended to be interesting as well as thought provoking And oh, by the way, all of the authors suffered strokes at some point in their lifetime “You only live once, but if you do it right, once is enough” Mae West Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Nebraska Home Office Life Underwriters Meeting Presentation 9/2014
Cases to Consider 2 cases arrive for underwriter review. Which has the worst mortality risk based upon the limited information provided? Case #1 66 y/o female with a hx. of a “TIA-like” event 4 years ago with no subsequent symptoms. Hx. of hypertension and hyperlipidemia. BMI 30 MRI of the brain WNL US of the carotids is WNL ECG is WNL CIMT at 90th percentile for age Case #2 65 y/o female with no known neurological complaints—past or present Hx. of hypertension and hyperlipidemia. BMI 30 MRI of the brain shows 2 small lacunar infarcts—age unknown US of the carotids is WNL ECG is WNL CIMT is WNL Cases described above are not actual cases but instead have been created to illustrate points made during this presentation. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

STROKES ECG Puzzler 6,400,000 stroke survivors
134,000 deaths each year 1 out of every 19 deaths 4th leading cause of death for Americans 795,000 Americans suffer strokes each year . Strokes are frequently recurrent. In fact nearly one of four CVA’s occur in people who have had a previous stroke 34% of people hospitalized for stroke in 2009 were under 65 years of age. STROKES ____ Facts to know Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Prevalence of stroke by age and sex
Chart 4-1. Prevalence of stroke by age and sex (NHANES: 1999–2004). Source: NCHS and personal communication with NHLBI. Rosamond W et al. Circulation 2007;115:e69-e171 Copyright © American Heart Association Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Stroke Facts : Annual stroke death rate fell 35%. Actual number of deaths fell 19%. Stroke is a leading cause of death in the United States behind heart disease and all forms of cancer combined. Approximately 795,000 Americans have a new or recurrent stroke each year. Stroke kills approximately 134,000 Americans each year. From 1996 to 2006, the stroke death rate fell 33.5% and actual number of stroke deaths fell by 18.4%. There are more than 6 million stroke survivors living in the United States. Men make up about 2,500,000 of survivors and women make up 3,900,000. About one-third have mild impairments, another third are moderately impaired and the remainder are severely impaired. References: American Heart Association. Heart Disease and Stroke Statistics 2010 Update At-a-Glance. At: Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

In just this time frame here (1998-2008):
Temporal trends in age-adjusted death rates for the top 10 causes of death in the United States from 1931 to 2008. 2nd most common cause of death world wide In 2008 CVA dropped from the 3rd most common cause of death in the US to the 4th. Towfighi A , and Saver J L Stroke 2011;42: Temporal trends in age-adjusted death rates for the top 10 causes of death in the United States from 1931 to 2008. In just this time frame here ( ): Annual stroke death rate fell 35%. Actual number of deaths fell 19%. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Mortality rate from Stroke Similar downward trend noted in the European Union. Point #1 The stroke mortality rate in the Western countries is declining. Decreased incidence Decreased case-fatality rate Point #2 The projected total number of US deaths from strokes is not expected to decline through 2030 however because of the aging population Trend between 1980 and 2005 stroke mortality rates (rates per 100,000 person-years, standardized using the European Union comprising 25 member states [EU25] population by 5 years as the standard population). Men and women in 7 European countries. Kunst A E et al. Stroke 2011;42: Copyright © American Heart Association Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Definitions TIA Classic Definition: Rapidly developing clinical signs of focal or global disturbance of cerebral function lasting fewer than 24 hours, with no apparent non-vascular cause. June 2009 AHA/ASA scientific statement definition: A transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction CVA An infarction of the central nervous system tissue References: Definition and Evaluation of Transient Ischemic Attack. A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke Council; Easton, Donald J et al Stroke :40: "You have enemies? Good. That means you’ve stood up for something, sometime in your life.“ Winston Churchill Definition and Evaluation of Transient Ischemic Attack. A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke Council; Easton, Donald J et al Stroke :40: Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Consequences of the definition change
Anticipate a drop in annual incidence of TIA’s by 33% Increase in diagnosis of CVA’s by 7%. There has been a change in the enrollment of members into studies Potential change in treatment guidelines in the future Mortality statistics impact Comparison of old statistics to newer and future statistics won’t be apples to apples Potential improvement in CVA morbidity and mortality results from earlier treatment. Decreased “wait and see” approach. References: American Heart Association. Heart Disease and Stroke Statistics 2010 Update At-a-Glance. At: Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Consequences of definition change---Consider 3 diagnosis outcomes
TIA No longer is this the poor prognostic event that it was 90 day risk of stroke with residual symptoms is <1% Image-positive transient event 90 day risk of stroke with residual symptoms is ~14% ~15 x the chance of having a stroke with residual symptoms in the next 7 days as compared to those with a stroke that already have residual neurological symptoms Ischemic stroke with residual neurological symptoms Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Annual risk for future stroke after an initial TIA or ischemic stroke
Annual risk is estimated at ~3-4%1 Great progress has occurred in preventing recurrent stroke2. 1960’s 8.71% 1970’s 6.1% 1980’s 5.41% 1990’s 4.04% Prevention aided by: Antiplatelet therapy/anticoagulation Atrial fibrillation treatments Hypertensive and hyperlipidemia treatments Arterial obstruction treatments 1. Kernan, Walter et al. Guidelines for the prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the AHA/AS. Stroke ; Accessed 5/5/2014 2 Hong KS, Yegiaian S, Lee M, Lee J, Saver JL. Declining stroke and vascular event recurrence rates in secondary prevention trials over the past 50 years and consequences for current trial design. Circulation. 2011;123:2111–2119. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

CVA’s are caused by anything that can cause vascular compromise
Heart Atrial fibrillation/rhythm disturbances VSD/PFO/Endocarditis Large Blood Vessels Thrombus Atherosclerosis Takayasu arteritis Giant cell arteritis Fibromuscular dysplasia Emboli Dissection Marfan’s syndrome and other similar conditions Intracranial Blood Vessels Same as large blood vessels but also includes Moya-Moya Rupture of the Blood vessel and bleeding Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Vascular Compromise Blood itself Bleeding Tendencies
Complication of anticoagulation medications Hemophilia Clotting Tendencies Protein C or S deficiency Prothrombin gene mutation Factor V Leiden Antithrombin III deficiency Hyperhomocysteinemia Antiphospholipid syndrome Essential thrombocytosis Sickle cell anemia Polycythemia Vera “Today was tomorrow yesterday so don`t inhale.” Mel Blanc Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

What type of vascular problem is occurring is important
Inflammation Atherosclerosis Lipohyalinosis Aneurysmal dilation Arterial dissection Thrombosis Embolus Rupture of a vessel in the subarachnoid space or intracerebral tissue Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Two Major Types of Stroke
Ischemia Thrombosis (local obstruction of an artery) Embolism (Debris or blood clot traveling from elsewhere and lodging in an artery causing obstruction) Systemic hypo-perfusion (general medical condition with lack of blood supply reaching the brain Hemorrhage Subarachnoid hemorrhage (bleeding into the CSF within the subarachnoid space around the brain) Intra-cerebral hemorrhage (bleeding directly into the brain tissue) “Death solves all problems, No man, no problem” Joseph Stalin Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

What type of vascular problem is occurring is important
Inflammation Atherosclerosis Lipohyalinosis Aneurysmal dilation Arterial dissection 80% of strokes are ischemic 20% of strokes are hemorrhagic Thrombosis Embolus Rupture of a vessel in the subarachnoid space or intracerebral tissue Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Where the vascular compromise occurs is important Brain cells have different functions in different locations Frontal Lobe Personality Memory Reasoning Temporal Lobe Speech Hearing Parietal Lobe Language Sensation Telling right from left Occipital Lobe Vision Cerebellum Balance Fine motor control Coordination Brain Stem Breathing Swallowing Blood Pressure Smell Hearing Speech Fingers Arm Hip Hand Language Vision Balance Coordination Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Anatomy of the cerebrovascular system Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

The size of the emboli impacts the size of the infarction
The vascular “tree” Strokes from atrial fibrillation are typically associated with more brain tissue involved when compared to carotid artery disease-induced strokes. Presumably due to larger emboli.

Subarachnoid Hermorrhage Intracerebral Hermorrhage
Blood vessel ruptures and blood leaks in between the brain and the skull Intracerebral Hermorrhage Blood vessel ruptures and bleeds directly into the brain tissue Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Neurological Symptoms---A helpful chart TIA—Making the diagnosis Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Several important points here:
Not all neurological symptoms are vascular in etiology TIA—Making the diagnosis Several important points here: There are several potential etiologies for transient neurological events If vascular compromise is of concern there ideally will be results of a typical diagnostic work-up for underwriter review to assess mortality risk Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

CVA—Making the diagnosis
Brain imaging with CT or MRI is indicated in all patients with a suspected TIA or minor non-disabling stroke as soon as possible. The 2013 AHA/ASA guidelines suggest: Imaging techniques and quality of the exams has evolved To some extent the type of imaging performed is based upon the availability of testing devices and expertise of staff Many feel that the Diffusion Weighted Imaging (DWI) MRI is more sensitive than CT for the early detection of acute ischemia. CT’s are frequently more accessible and are frequently used—especially first tests. CT’s are also especially good at detecting the presence of hemorrhage. Imaging within 24 hours of symptom onset MRI and specifically Diffusion-Weighted Imaging MRI as the preferred modality Noninvasive imaging (MRA, CTA of the cervico-cephalic vessels) to be part of the evaluation of suspected TIA’s or non-disabling strokes Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

CVA—Making the diagnosis
Cardiac evaluation is important when TIA or CVA is suspected. Testing frequently performed include: ECG Echocardiogram Cardiac monitoring Other tests are performed as needed Blood cultures Sed rate CBC PT/PTT “My formula for living is quite simple. I get up in the morning and I go to bed at night. In between, I occupy myself as best I can” Cary Grant Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Making the diagnosis of a CVA
Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Thalamocapsular region
DWI T2 weighted FLAIR Cerebellum region Thalamocapsular region

Dissection Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Primary treatment of an acute ischemic CVA or TIA
Acute Ischemic strokes: Thrombolytic therapy with intravenous alteplase (tPA—recombinant tissue-type plasminogen activator) Early treatment important Many exclusions Unfortunately, in the US only about 8% of all ischemic stroke victims present to the ER within 3 hours and also meet the eligibility criteria for tPA. Vertebral artery or Carotid artery dissecting aneurysms Thrombolytic therapy is not contraindicated and the effectiveness and safety is comparable to ischemic strokes from other causes Extension of the aortic dissection is a potential complication of the thrombolysis however. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Primary treatment of an acute bleed
Subarachnoid hemorrhage Aneurysmal (~80%) Surgical management usually needed Surgical clipping Endovascular therapy with coil system Non-aneurysmal (~20%) AVM Endovascular therapy Intracranial artery dissection Perimesencephalic non-aneurysmal subarachnoid hemorrhage Subtype identified in 1985 Findings of localized blood on CT, normal angiography, and a relatively benign course Long term mortality is significantly better than aneurysmal SAH approaching normal controls. Intra-cerebral bleeding Reversal of anticoagulation Monitoring of intracranial pressure Seizure prophylaxis Surgery for cerebellar decompression and possibly supratentorial ICH (controversial) Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

BREAKING NEWS!!!! May 2014 Development

Secondary Treatment of the acute ischemic CVA or TIA
Smoking cessation Heavy ETOH consumption should be avoided but light to moderate consumption (no more than 2 per day for men and 1 drink per day for women) is reasonable Physical exercise—30 min of moderate-intensity for 30 min or more 1-3 times per week Antiplatelet therapy initiation within 24 hours of stroke and continued for 90 days BP management—Goal of therapy is BP of <140/90 mm Hg. Lipid lowering therapy (Statins) for those with elevated LDL >100 mg/dl. Prophylaxis for DVT and PE important for those at risk DM management (Diabetics have twice the typical risk for CVA). Unfortunately studies have not provided conclusive evidence that tight control decreases macro-vascular disease similar to the benefit in micro-vascular disease. The AHA/ASA still supports good control of blood sugars however. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014 Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack. A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke. 2011; 42:

Secondary Treatment of the acute ischemic CVA or TIA—Slide 2
Atrial Fibrillation (paroxysmal or permanent): Anticoagulation with a vitamin K antagonist, apixaban, dabigatran, or rivaroxaban are indicated ASA alone for those who can’t tolerate a vitamin K antagonist Prosthetic heart valves Oral anticoagulation recommended ASA is recommended to be added to the oral anticoagulation for those with an ischemic event while on anticoagulation Cardiomyopathy with EF <35%: Warfarin, ASA, Clopidogrel, or the combo of ASA and dipyridamole may be considered. It is unclear which is more advantageous. Non-cardioembolic ischemic strokes or TIA’s Antiplatelet therapy PFO (Patent Foramen Ovale) Antiplatelet therapy is recommended for those not obtaining anticoagulation. Data doesn’t support closure for those with PFO and TIA/cryptogenic ischemic stroke if no evidence of DVT Consider surgical closure with a trans-catheter device for those with PFO and DVT. Acute MI and left ventricular thrombus Oral anticoagulation recommended for at least 3 months Arterial Dissection Antithrombotic treatment with either antiplatelet or anticoagulant therapy for 3-6 months Endovascular stenting should be considered for recurrent ischemic events despite medical treatment Surgical treatment should be considered for those failing stenting. PFO closure. RESPECT and PC trial results published in the NEJM early PC Trial involved 414 patients. RESPECT involved 980 patients. Both randomized patients to either medical therapy or PFO closure after suffering an ischemic stroke or TIA. No benefit of closure in the main, intention-to-treat- analysis. However in the RESPECT trial there was benefit to closure in a “as-treated_ analysis. Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack. A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke. 2011; 42:

Secondary Treatment of the acute ischemic CVA or TIA
Symptomatic recent (within last 6 months) extracranial carotid disease: 70-99% stenosis of ipsilateral side: Carotid endarterectomy recommended When morbidity and mortality risk is <6% 50-69% stenosis: Carotid endarterectomy to be considered When morbidity and mortality risk is <6% and Dependent on pt specific factors (age, sex, comorbid conditions) <50% stenosis No indication for endarterectomy or stenting Carotid angioplasty and stenting is an alternative in some settings > 70% stenosis by noninvasive testing Especially those difficult to assess surgically such as radiation induced stenosis or restenosis after endarterectomy > 50% stenosis by angiography Optimal medical therapy including antiplatelet therapy, statins, etc. Extracranial vertebrobasilar disease: Optimal medical therapy Consider surgery when medical therapy has failed. Intracranial atherosclerosis 50-99% stenosis: ASA recommended (in preference to warfarin) Angioplasty and/or stent placement usefulness is unknown and considered E/I for those 70-99% stenotic. It is not recommended for those <70% stenotic. Bypass surgery is not recommended “There is nothing so strong or safe in an emergency of life as the simple truth” Charles Dickens Nebraska Home Office Life Underwriters Meeting Presentation 9/2014 Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack. A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Furie, Karen et al. Stroke. 2011; 42:

Mortality implications of TIA’s and CVA’s
TIA without images being positive 90 day stroke risk <1% Transient event that is image positive 90 day stroke risk 14% CVA CVA’s have a high peri-stroke period mortality rate Complications clearly are determined by Location of the stroke How much brain tissue is involved 95% of patients have at least one medical complication1 24% of patients have at least one serious, life threatening complication1 Direct effects of the stroke cause death in the first few days. Medical complications account for the mortality thereafter In the first year the most common cause of death is2: First week: Cerebrovascular disease 2-4 weeks: PE 2-3 months: Pneumonia >3 months Cardiac disease 1Randomized trial of Tirilizad Mesylate in Acute Stroke (RANTTAS) 2Risk of myocardial infarction and vascular disease after transient ischemic stroke and ischemic stroke: a systematic review and meta-analysis. Touze E et al Stroke :36 (12):2748

Cardiac complications of a stroke
Cardiac complications are not just the association of atherosclerosis Stroke is a coronary artery disease risk equivalent Those with a stroke with no known coronary disease have a similar risk of MI as those with established coronary disease Takotsubo cardiomyopathy is one condition that can occur Extreme catecholamine release is postulated to cause this Causes an acute cardiomyopathy Interestingly it typically involves the apical and mid sections of the heart ECG abnormalities present in 92% of patients with an acute stroke Classic large and upright T waves can occur Prolonged QT intervals are common Cardiac arrhythmias Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Included those with hx. of heart disease Did not include those with hx. of heart disease Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

4 QUESTIONS What percentage of stroke victims die within 1 month of their first stroke? What percentage of stroke victims die within 5, 10 and 15 years? Does age matter? Does type of stroke matter? Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Proportion of patients dead 1 year after first stroke.
>64 y/o 45-64 y/o Proportion of patients dead 1 year after first stroke. Source: Pooled data from the Framingham Heart Study, Atherosclerosis Risk in Communities study, and Cardiovascular Health Study of the National Heart, Lung, and Blood Institute. Go A S et al. Circulation 2013;127:e6-e245 Nebraska Home Office Life Underwriters Meeting Presentation 9/2014 Copyright © American Heart Association

Proportion of patients dead within 5 years after first stroke.
>64 y/o 45-64 y/o Proportion of patients dead within 5 years after first stroke. Source: pooled data from the Framingham Heart Study, Atherosclerosis Risk in Communities study, and Cardiovascular Health Study of the National Heart, Lung, and Blood Institute. Compared to the general population nonfatal stroke is associated with a: 5 fold increase for death between 1 month and 1 year. 2 fold increase for death at 5 years Writing Group Members et al. Circulation 2012;125:e2-e220 Nebraska Home Office Life Underwriters Meeting Presentation 9/2014 Copyright © American Heart Association

Figure 1. Short-term survival probability for patients aged 65 years at first nonfatal stroke by subtype (Cox regression). Estimated cumulative risk for death: 28 days 28% 1 year 41% 5 years 60% However, risk of death did vary based upon type of stroke IDS Ill Defined Stroke CI Cerebral Infarct SAH Subarachnoid Hemorrhage PICH 1o Intracerebral Bleed Part of the World Health Organizations (WHO) MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Project. 4,162 patients with a first stroke eligible for analysis Copyright © American Heart Association Brønnum-Hansen H et al. Stroke 2001;32: Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Figure 2. Long-term survival probability for patients aged 65 years at first nonfatal stroke by subtype (Cox regression). Estimated cumulative risk for death: 5 years 60% 10 years 76% 15 years 86% SAH Subarachnoid Hemorrhage SAH Subarachnoid Hemorrhage CI Cerebral Infarct PICH 1o Intracerebral Bleed IDS Ill Defined Stroke Figure 2. Long-term survival probability for patients aged 65 years at first nonfatal stroke by subtype (Cox regression). PICH, primary intracerebral hemorrhage; CI, cerebral infarct; and IDS, ill-defined stroke patients. Brønnum-Hansen H et al. Stroke 2001;32: Nebraska Home Office Life Underwriters Meeting Presentation 9/2014 Copyright © American Heart Association

Vascular event (with 95% CI)
Mortality Stroke A well-designed prospective cohort study of 2447 participants from the Dutch TIA trial found that the risk for major vascular events and stroke was highest shortly after TIA or minor nondisabling stroke, declined to its lowest point at about three years, and then progressively increased over the remainder of the 10-year follow-up (figure 4) [19]. In contrast, the risk for mortality gradually rose throughout the study. By 10 years, 60 percent had died and 54 percent had experienced new vascular events (stroke and myocardial infarction). Event-free survival was 48 percent. Predictive factors for risk of vascular events and death included age over 65 years, diabetes, claudication, previous vascular surgery, and pathologic Q waves on baseline electrocardiogram. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

The Mortality Risk Evaluation Needs to be Individualized
Age Interventions done after the CVA Infarct Location Individual Prognosis Stroke Severity Adherence to therapeutic plan Stroke Mechanism Clinical Findings Complications Comorbid conditions Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Imaging results frequently encountered by the underwriting staff
3 tests, frequently seen, that I want to discuss in more depth are: CIMT testing Carotid Duplex Ultrasound testing MRI or CT scan which shows the presence of a previous infarct—incidental finding “If you want to stay young-looking, pick your parents very carefully” Dick Clark Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Carotid artery intima-media thickness (CIMT)
CIMT measures the thickness of 2 layers (intima and media) of the carotid artery walls Carotid artery methods are being refined so it is important to know exactly where the artery is being measured (Carotid bulb, common carotid, or internal carotid), near or far walls or both. /S (05) /abstract Thought by some to be an even earlier indicator of atherosclerosis than Coronary artery calcium measurements since thickening precedes a plaque

Carotid artery intima-media thickness (CIMT)
Abnormal (“high risk”) frequently defined as media thickness above the 75th percentile. Conflicting evidence whether this test has independent predictive power as compared to usual CV risk factors American Heart Association Position Statement (dated 3/7/12) even suggested this test not be mandated by health insurers as the predictive power hasn’t been established. (Of note however is that they also did not support EBCT measurements whereas there is some evidence this test is helpful, at least in intermediate risk individuals, independently of other tests). In the Multi-Ethnic Study of Atherosclerosis (MESA) which had 6698 subjects aged years CIMT was a modestly better predictor of stroke than EBCT but was not as good as EBCT for CV disease prediction Meta-analysis has shown that serial measurements are not useful for predicting progression. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

US and MRA Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Evaluation of the Carotid arteries
Carotid duplex ultrasound frequently performed: 81-98% sensitive 82-89% specific Less precise for stenosis of <50% Less precise for stenosis of 100% Frequently used with MRA or CTA for confirmation of stenosis of >50% or for 100% stenosis. Complete Obstruction: No surgical treatment has been proven to be of benefit. Combo of US and MRA very good at detecting this CTA is also extremely good at detecting this Gold standard is angiography Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Asymptomatic extracranial carotid artery disease
The 2011 AHA/ASA Guidelines Medical therapy and lifestyle changes should be instituted Population screening for asymptomatic carotid artery stenosis is not recommended Benefit in women is very controversial Prophylactic CEA performed with <3% morbidity and mortality should be considered when: Minimum of 60% occlusion by angiography or >/= 70% occlusion on doppler >80% occlusion on CTA or MRA for those with US showing 50% to 69% stenosis The number to treat (NTT) to prevent 1 stroke over 3 years is 33 Carotid artery stenting can be considered but the advantage over medical therapy is not well established “If you act like you know what you are doing, you can do anything you want – except neurosurgery” Sharon Stone Bonus Quote: “I like to drive with my knees. Otherwise, how can I put on my lipstick and talk on the phone” Sharon Stone Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack. A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Furie, Karen et al. Stroke. 2011; 42:

Silent Strokes A not so uncommon incidental finding
Not such good outcomes when found Evaluated in the Cardiovascular Health Study1 Published in 2002 5888 people >/= 65 y/o with normal MRI followed by repeat MRI in 5 years. 17.7% had 1 or more infarct Only 11% had experienced a documented TIA or CVA . Those with + MRI scans showed > decline in Mini-Mental exam test results Evaluated in the Rotterdam Scan study2 Published in 2003 1077 elderly people followed for over 4 years. Silent brain infarcts increased the chance of a subsequent major CVA by 5 times. Those with >1 silent infarct were at the highest risk for a subsequent major CVA. The presence of silent infarcts significantly increased the risk of dementia Silent strokes typically involve small areas of the brain or areas that have tremendous amount of potential for redundancy....not areas like the pre-Rolandic motor cortex area containing the pars opercularis or its connections which would result in Broca’s aphasia. 1. Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: The Cardiovascular Health Study. Longstreth WT et al Stroke. 2002;33(10):2376. 2. Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Vermeer SE, et al, Rotterdam Scan Study Stroke. 2003;34(5):1126 Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

More examples of silent CVA’s Axial T2-weighted Axial T1-weighted FLAIR Axial Proton Density Main signal characteristics used for defining SBI on different MRI sequences. A–D, A silent brain infarct (SBI) corresponds to CSF signal on all MRI sequences (black arrows). A, Axial T2-weighted; (B) axial T1-weighted; (C) axial fluid-attenuated inversion-recovery (FLAIR); (D) axial proton density. E–H, A hyperintense lesion on T2-weighted images that is moderately hypointense on T1 in the left thalamus (white arrows) is not defined as SBI in studies defining only cavities containing CSF as infarcts, whereas it is diagnosed as an infarct in studies that simply defined hyperintense T2 and hypointense T1 foci as infarcts. E, Axial T2-weighted; (F) axial T1-weighted; (G) axial FLAIR; (H) axial proton density. CSF indicates cerebrospinal fluid. Zhu Y et al. Stroke 2011;42: Nebraska Home Office Life Underwriters Meeting Presentation 9/2014 Copyright © American Heart Association

Summary CVA rates in the US are declining. However, based upon population demographics the total number/year is anticipated to continue to rise Definition changes regarding TIA and CVA will impact mortality numbers There are several types of strokes and multiple etiologies. Regardless of the type there are significant adverse long term mortality concerns Diagnosis of TIA’s and CVA’s can be accomplished with several types of imaging. A diffusion weighted MRI probably is one of the best methods. Quick evaluation is important Primary and secondary treatment depends on the etiology of the stroke but does impact mortality CIMT testing might demonstrate future potential value in underwriting but as an independent cardiac or cerebrovascular disease indicator there are currently conflicting results Carotid US results and the presence of CVA’s found incidentally do help with underwriting Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Cases to Consider 2 cases arrive for underwriter review. Which has the worst mortality risk based upon the limited information provided? Case #1 66 y/o female with a hx. of a “TIA-like” event 4 years ago with no subsequent symptoms. Hx. of hypertension and hyperlipidemia. BMI 30 MRI of the brain WNL US of the carotids is WNL ECG is WNL CIMT at 90th percentile for age Case #2 65 y/o female with no known neurological complaints—past or present Hx. of hypertension and hyperlipidemia. BMI 30 MRI of the brain shows 2 small lacunar infarcts—age unknown US of the carotids is WNL ECG is WNL CIMT is WNL Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Questions? Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Stroke; A Journal of Cerebral Circulation Lifelong Rupture Risk of Intracranial Aneurysms Depends on Risk Factors: A Prospective Finnish Cohort Study Stroke 2014 May 22;[EPub Ahead of Print], M Korja, H Lehto, S Juvela Lifelong Risk for Rupture of Intracranial Aneurysms Take-HOME MESSAGE Of 118 people, 34 (29%) had subarachnoid hemorrhage (SAH) during lifelong follow-up after diagnosis of unruptured intracranial aneurysm (UIA). The median age at SAH was 51.3 years. The annual rupture rate per patient was 1.6%. Risk factors for a lifetime SAH included female sex, current smoking, and aneurysm size of ≥7 mm in diameter. Depending on the risk factor burden, the annual rupture rate was from 0% to 6.5%, and the lifetime risk of an aneurysmal SAH varied from 0% to 100%. Of 96 patients with small (<7 mm) UIAs, 24 (25%) had an aneurysmal SAH during the follow-up. Although risk was associated with the risk factor burden, close to 30% of the aneurysms in working-age people ruptured over the course of lifelong follow-up. The results suggest that maybe risk factor status should drive treatment decisions for individuals with UIAs given that even the small ones in this study ruptured. ABSTRACT Background and Purpose Our aim was to define for the first time the lifelong natural course of unruptured intracranial aneurysms (UIAs) and identify high-risk and low-risk patients for the rupture. Methods One hundred and eighteen patients (61 women) with UIAs were diagnosed between 1956 and 1978 and followed up until death or subarachnoid hemorrhage (SAH). The median age at the diagnosis was 43.5 years (range, 22.6–60.7 years). The median size of the UIA at the diagnosis was 4 mm (range, 2–25 mm). Analyzed risk factors for a rupture included sex, age, cigarette smoking, systolic blood pressure values, diagnosed hypertension, UIA size, and number of UIAs. Results Thirty four (29%) out of 118 people had SAH during the lifelong follow-up. The median age at SAH was 51.3 years (range, 30.1–71.8 years). The annual rupture rate per patient was 1.6%. Female sex, current smoking, and aneurysm size of ≥7 mm in diameter were risk factors for a lifetime SAH. Depending on the risk factor burden, the lifetime risk of an aneurysmal SAH varied from 0% to 100%, and the annual rupture rate from 0% to 6.5%. Of the 96 patients with small (<7 mm) UIAs, 24 (25%) had an aneurysmal SAH during the follow-up. Conclusions Almost 30% of all UIAs in people of working age ruptured during a lifelong follow-up. The risk varied substantially on the basis of risk factor burden. Because even small UIAs ruptured, treatment decisions of UIAs should perhaps be based on the risk factor status. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Stroke; A Journal of Cerebral Circulation Long-Term Mortality After First-Ever and Recurrent Stroke in Young Adults Stroke 2014 Jul 24;[EPub Ahead of Print], K Aarnio, Elena Haapaniemi, S Melkas, M Kaste, T Tatlisumak, J Putaala Background and Purpose Mortality after first-ever stroke, and particularly after recurrent stroke, and predictors of long-term mortality among young and middle-aged stroke patients are not well-known. We assessed 17-year risk of mortality with focus on the effect of recurrence on the risk of death of young and middle-aged patients with stroke. Methods Mortality and recurrent stroke rate of 970 consecutive 30-day survivors of first-ever ischemic stroke aged 15 to 49 years (1994–2007) were studied. Prospective follow-up data came from the Finnish Care Register for Health Care and Statistics Finland. Mean follow-up was 10.2±4.3 years. We compared survival between clinical subgroups and identified factors associated with mortality. Standardized mortality ratio was calculated for demographic and pathogenetic subgroups using mortality data of the general population matched with age, sex, calendar year, and geographical area. Results At the end of follow-up, 152 (15.7%) patients had died (cumulative risk, 23.0%; 95% confidence interval, 19.1%–26.9%) and 132 (13.6%) had experienced a recurrent stroke. After adjusting for baseline characteristics, recurrent stroke was statistically the most important risk factor for mortality after first-ever ischemic stroke (hazard ratio, 16.68; 95% confidence interval, 2.33–119.56; P=0.005). Observed mortality was 7-fold higher than the expected mortality (standardized mortality ratio, 6.94; 95% confidence interval, 5.84–8.04) and particularly high among patients who experienced a recurrent stroke (standardized mortality ratio, 14.43; 95% confidence interval, 10.11–18.74). Conclusions The high mortality rates and the striking impact of recurrent stroke on the risk of death should lead to development of more robust primary and secondary prevention strategies for young patients with stroke. Nebraska Home Office Life Underwriters Meeting Presentation 9/2014

Cerebrovascular Disease: A Discussion of Strokes and TIA’s

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Cerebrovascular Disease: A Discussion of Strokes and TIA’s

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