DISCLOSURES RISK ASSESSMENT. Stroke and Heart Disease -Is there a Link Beyond Risk Factors? Daniel Lackland, MD

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1 STROKE AND HEART DISEASE IS THERE A LINK BEYOND RISK FACTORS? D AN IE L T. L AC K L AN D DISCLOSURES Member of NHLBI Risk Assessment Workgroup RISK ASSESSMENT Count major risk factors For patients with multiple (2+) risk factors Perform 10-year risk assessment For patients with 0 1 risk factor 10 year risk assessment not required Most patients have 10-year risk <10% 1

2 Modifiable risks Cardiovascular Disease Hypertension CAD/CHF Diabetes Dyslipidemia High total Cholesterol and/or Low HDL Atrial Fibrillation Asymptomatic Carotid Artery Stenosis Cigarette smoking Sickle Cell Disease Dietary Factors Obesity Physical Activity Hormone Replacement Therapy Less Well-Documented or Potentially Modifiable Risk Factors Metabolic syndrome Alcohol abuse Hyperhomocysteinemia Drug abuse Hypercoagulability Oral contraceptive use Inflammatory processes Periodontal disease, C pneumoniae, Cytomegalovirus, H pylori CagA seropositivity, Acute infection, elevated hs-crp Migraine Sleep disordered breathing AGE Non-modifiable risks Doubling of stroke rate each 10 years after age 55 White Black Men Women Men Women Prevalence (per 100,000) 2

3 Equating risk factors with actual risk Patients should have stroke risk assessment (Class I, Level A) Risk assessment tools should be considered (Class IIa, Level B) Helps identify individuals who could benefit from therapeutic interventions and who may not be treated on the basis of any 1 risk factor ASSESSMENT OF CHD RISK For persons without known CHD, other forms of atherosclerotic disease, or diabetes: Count the number of risk factors: Cigarette smoking Hypertension (BP 140/90 mmhg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dl) Family history of premature CHD o CHD in male first degree relative <55 years o CHD in female first degree relative <65 years Age (men 45 years; women 55 years) Use Framingham scoring for persons with 2 risk factors* (or with metabolic syndrome) to determine the absolute 10-year CHD risk. (downloadable risk algorithms at Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285: , Professional Postgraduate Services MODIFIED APPROACH TO CHD RISK ASSESSMENT LOW RISK designated as <0.6% CHD risk per year (<6% in 10 years) INTERMEDIATE RISK designated as a CHD risk of 0.6%- 2.0% per year (6-20% over 10 years) HIGH RISK designated as a CHD risk of >2% per year (20% in 10 years) (CHD risk equivalent), including those with CVD, diabetes, and PAD Greenland P et al. Circulation 2001; 104:

4 Modified Framingham Stroke Risk Profile (men) Points _ Age SBP (Untreated) SBP (Treated) Diabetes No Yes Cigarette No Yes CVD No Yes A Fib No Yes LVH on No Yes EKG Modified Framingham Stroke Risk Score 10-Year Probability, % Points Men Women Year Probability, % Points Men Women Risk Factor High Risk Caution Low Risk Blood Pressure > 140/ /80-89 <120/80 or I don t know Cholesterol > <200 or I don t know Diabetes Yes Borderline No Smoking I still smoke Atrial Fibrillation I have an irregular I don t know My heartbeat is heartbeat regular Diet I am overweight I am slightly My weight is overweight healthy Exercise I am a couch potato I exercise sometimes I exercise regularly I have stroke in Yes not sure no My family Score (each box=1) 4

5 Risk assessment tool pitfalls Each tool has limitations Do not account for all risk factors Need to be validated against different ethnic/race groups Have not yet been shown to improve stroke prevention programs Examination: Height: 6 ft 2 in Weight: 220 lb (BMI 28 kg/m 2 ) Waist circumference: 41 in BP: 150/88 mm Hg P: 64 bpm RR: 12 breaths/min Cardiopulmonary exam: normal Laboratory results: TC: 220 mg/dl HDL-C: 36 mg/dl LDL-C: 140 mg/dl TG: FBS: 220 mg/dl 120 mg/dl PRESENTATION WHAT IS WJC S 10-YEAR ABSOLUTE RISK OF FATAL/NONFATAL MI? A 12% absolute risk is derived from points assigned in Framingham Risk Scoring to: Age: 6 TC: 3 HDL-C: 2 SBP: 2 Total: 13 points In 1992 he exercised 14 minutes in a Bruce protocol exercise stress test to 91% of his maximum predicted heart rate without any abnormal ECG changes. He started on a statin in But in Sept 2004, he needed urgent coronary bypass surgery. 5

6 CHD RISK EQUIVALENTS Risk for major coronary events equal to that in established CHD 10-year risk for hard CHD >20% Hard CHD = myocardial infarction + coronary death DIABETES AS A CHD RISK EQUIVALENT 10-year risk for CHD 20% High mortality with established CHD High mortality with acute MI High mortality post acute MI CHD RISK EQUIVALENTS Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) Diabetes Multiple risk factors that confer a >20% 10-year risk for CHD 6

7 NOT ALL INDIVIDUALS WITH CORONARY HEART DISEASE HAVE TRADITIONAL RISK FACTORS 3 RF 9% 4 RF 1% 0 RF 19% 2 RF 28% 1 RF 43% Khot et al. JAMA 2003 Is there clinical evidence that novel risk markers predict future coronary events and provide additional predictive information beyond traditional risk factors? THE FUTURE OF CARDIAC BIOMARKERS Many experts are advocating the move towards a multimarker strategy for the purposes of diagnosis, prognosis, and treatment design As the pathophysiology of ACS is heterogeneous, so must be the diagnostic strategies 7

8 RISK ASSESSMENT IN PRACTICE Standard risk factors alone or in combination do not predict global risk well enough o Too many events in too many lower risk individuals o Modest screening performance Insufficient data at the present time to recommend novel biomarkers to screen the population at large, but selected intermediate risk populations may be appropriate. TREATMENT SUMMARY Individual biomarkers do not markedly improve risk prediction Markers of existing disease most promising (including imaging tools) Combining individual markers that reflect distinct biological pathways is a promising strategy, with several caveats Combining multiple mediocre markers will not work Not close to ready for clinical application Cost-effectiveness and outcome studies needed STROKE AS A RISK EQUIVALENT: PERCENTAGE OF PARTICIPANTS WITH LEVELS OF RISK BY AGE (DATA FROM REGARDS Lackland et.al Stroke 43: ,

9 STROKE AS CHD RISK EQUIVALENT Patients with atherosclerotic stroke should be included among those deemed to be at high risk (20% over 10 years) of further atherosclerotic coronary events. For the purposes of primary prevention, ischemic stroke should be included among cardiovascular disease outcomes in absolute risk assessment algorithms. The inclusion of atherosclerotic ischemic stroke as a high-risk condition and the inclusion of ischemic stroke more broadly as an outcome will likely have important implications for prevention of cardiovascular disease, because the number of patients considered to be at high risk would grow substantially. (Stroke.2012;43:00-00.) Large-vessel atherosclerotic ischemic stroke should be considered as a CHD risk equivalent similar to other atherosclerotic conditions in risk prediction instruments and guidelines that use CHD risk equivalents (Class I; Level of Evidence B). Ischemic stroke can reasonably be considered a relevant outcome along with CHD outcomes in CVD risk prediction instruments used in primary and secondary prevention, including trials of general preventive strategies not focused on particular blood vessels (Class IIa; Level of Evidence B). 9

10 Ischemic stroke subtypes other than large-vessel atherosclerosis, including small-vessel disease, may be considered CHD risk equivalents, although further research is needed (Class IIb; Level of Evidence B). Hemorrhagic strokes and strokes of undetermined subtypes may be included among outcomes in general CVD risk prediction instruments used in primary and secondary prevention (Class IIb; Level of Evidence B). Ischemic stroke can reasonably be considered a relevant outcome in clinical 10-year cardiovascular risk prediction instruments for patients (Class IIa; Level of Evidence B). 10

11 Further clinical epidemiological studies are needed to increase the level of evidence to improve precision of the absolute risk estimates for different stroke subtypes in risk prediction instruments. Approach to Secondary Stroke Prevention Components: Evaluate the Event Implement Interventions Initiate Medications Modify Stroke Risk Factor: Continuous Monitoring Treating Hypertension to Prevent Stroke HTN is the single most important modifiable risk factor for stroke HTN contributes to 70% of all strokes 11

12 Benefits of Treating Hypertension Younger than 60 yrs Reduces the risk of stroke by 42% Reduces the risk of coronary event by 14% Older than 60yrs Reduces overall mortality by 20% Reduces cardiovascular mortality by 33% Reduces incidence of stroke by 40% Reduces coronary artery disease by 15% Treat Hypertension Aggressively Target most patients still < 140/90 Home Measurement: < 135/85 Diabetics or chronic kidney disease: < 130/80 Lifestyle Modification: Sodium restriction, DASH diet, physical activity, weight loss, alcohol restriction, smoking cessation Expect to use combination therapy ACE inhibitor, ARB, diuretic 12