1. CHAPTER 6 CEREBROVASCULAR DISEASE AND STROKE “APOPLEXY IS A STROKE OF GOD’S HANDS.” OXFORD ENGLISH DICTIONARY, 1599

2. STROKE: LOSS OR IMPAIRMENT OF BODY FUNCTION RESULTING FROM INJURY OR DEATH OF BRAIN CELLS FOLLOWING INSUFFICIENT BLOOD SUPPLY. TIA (TRANSIENT ISCHEMIC ATTACK): IS NOT A STROKE BUT IT CAN BE PRODROMAL (EARLY) SYMPTOM. PRECEDES ABOUT 15% OF STROKES AND ARE A MAJOR RISK FACTORS—ESPECIALLY FOR OLDER PEOPLE. FIVE COMMON SIGNS OF STROKE: (1) SUDDEN NUMBNESS OR WEAKNESS OF THE FACE, ARM, LEG, ESPECIALLY ON ONE SIDE OF THE BODY (2) SUDDEN CONFUSION AND TROUBLE SPEAKING OR UNDERSTANDING (3) SUDDEN TROUBLE SEEING IN ONE OR BOTH EYES (4) SUDDEN TROUBLE WALKING, DIZZINESS, OR LOSS OF BALANCE OR COORDINATION (5) SUDDEN, SEVERE HEADACHE WITH NO KNOWN CAUSE. ABOUT 85% OF STROKES ARE CLASSIFIED AS PRIMARY ISCHEMIC OR THROMBOSIS (CLOTTING IN A VESSEL) USUALLY FROM ATHEROSCLEROSIS OR FROM EMBOLISM (OCCLUSION OF A VESSEL BY A CIRCULATING ATHEROMA OR CLOT, OFTEN FROM THE HEART). ANOTHER10% RESULT FROM BLEEDING N THE BRAIN— PRIMARY INTRACEREBRAL HEMORRHAGIC STROKES.

3. MAGNITUDE OF THE PROBLEM P-125 CEREBROVASCULAR DISEASE (CVD) KILLED ABOUT 4.4 MILLION WORLDWIDE IN 1990, SECOND ONLY TO CHD. A DECADE LATER IT KILLED 5.4 MILLION. BLACKS IN THE US HAVE ALMOST TWICE THE RISK OF FIRST EVER STROKE COMPARED WITH WHITES. AGE-ADJUSTED RATES PER 1000 PEOPLE AGED 45 TO 84 YEARS ARE 6.6 IN BLACK MALES, 3.6 IN WHITE MALES, 4.9 IN BLACK FEMALES, AND 2.3 IN WHITE FEMALES. ABOUT1/3 OF PEOPLE WHO HAVE HAD 1 OR MORE TIA’S HAVE A STROKE WITHIN 5 YEARS. AMONG PEOPLE AGES 45 TO 64, 8% TO 12% OF ISCHEMIC STROKES AND 37% TO 38% OF HEMORRHAGIC STROKES RESULT IN DEATH WITHIN 30 DAYS. IN ADDITION TO MORTALITY, STROKE IS ALSO THE LEADING CAUSE OF ADULT DISABILITY IN THE US. (BODY FUNCTIONS, GAIT PROBLEMS, IMPAIRED VISION, SPEECH, COMPREHENSION, DEPRESSION, MEMORY LOSS AND PARALYSIS). STROKE HAS BEEN THE 3 RD LEADING CAUSE OF DEATH IN THE US SINCE 1938.

4. RISK FACTORS FOR STROKE AGE: STROKE RISK DOUBLES EACH DECADE AFTER AGE 55. TWO-THIRDS OF STROKE OCCUR IN PEOPLE OLDER THAN 65. SEX: WOMEN HAVE SLIGHTLY HIGHER STROKE RISK AND ARE MORE LIKELY TO DIE FROM STROKE THAN A MAN BUT MEN DIE SOONER THAN WOMEN FROM OTHER CAUSES SO THERE ARE MORE FEMALE THAN MALE STROKE SURVIVORS IN THE US. RACE: BLACKS HAVE 2 X THE RISK OF STROKE OF OTHER AMERICANS MAYBE BECAUSE THEY HAVE MORE OF THE OTHER KEY RISK FACTORS. ATRIAL-FIB: IRREGULAR CONTRACTION OF THE HEARTS ATRIA CAUSES AN IRREGULAR HB WHICH CAN LEAD TO POOLING OF BLOOD IN THE HEART AND CONTRIBUTE TO CLOT FORMATION AND ISCHEMIC STROKE. CHD: ATHEROSCLEROSIS UNDERLIES BOTH CAD AND CAROTID ARTERY DISEASE AND IS THUS A MAIN CAUSE OF ISCHEMIC STROKE—HENCE, PEOPLE WITH CHD ARE AT INCREASED RISK OF STROKE.

5. OBESITY, HYPERCHOLESTEROLEMIA, AND PHYSICAL INACTIVITY ARE SECONDARY CONTRIBUTING RISK FACTORS TO STROKE. MODIFIABLE RISK FACTORS: HYPERTENSION, SMOKING, ALCOHOL ABUSE, HYPERCHOLESTEROLEMIA, DIABETES AND OBESITY. HYPERTENSION: THE PRIMARY RISK FACTOR FOR THE DEVELOPMENT OF STROKE. EFFECTIVE CONTROL OF HYPERTENSION APPEARS TO REDUCE THE RISK OF STROKE BY ABOUT 40%. SMOKING: DAMAGES ARTERIES AND FURTHERS ATHEROSCLEROSIS. ALCOHOL ABUSE: ETOH HAS BEEN SHOWN TO INCREASE AND DECREASE THE RISK FOR STROKE. HYPERCHOLESTEROLEMIA: ASSOCIATED WITH ONLY A MODERATE INCREASE IN RISK FOR STROKE—STATIN DRUGS THOUGH, MAY REDUCE THICKENING OF THE CAROTID ARTERY WALL AND THUS REDUCE THE FREQUENCY OF STROKES BY ABOUT 30%. OBESITY & DIABETES: OVERWEIGHT (BMI) IS AN INDEPENDENT RISK FACTOR FOR STROKE AND IN YOUNG ADULTS STROKE IS NEARLY 12 X HIGHER IN THOSE WITH DIABETES—POSSIBLY EXPLAINED BY MICROVASCULAR DISEASE. [STATINS ARE A CLASS OF DRUGS USED TO LOWER CHOLESTEROL LEVELS BY INHIBITING THE ENZYME HMG-COA REDUCTASE, WHICH PLAYS A CENTRAL ROLE IN THE PRODUCTION OF CHOLESTEROL IN THE LIVER, WHICH PRODUCES ABOUT 70 PERCENT OF TOTAL CHOLESTEROL IN THE BODY].

6. ETIOLOGY OF STROKE PATHOPHYSIOLOGY INVLOVES ATHEROSCLEROTIC DISEASE AND HEMOSTATIC DYSFUNCTION SIMILAR TO CHD. EMBOLIC STROKE: (ISCHEMIC STROKE) CAUSED BY BLOCKAGE OF ONE OF THE ARTERIES TO THE BRAIN BY A BLOOD CLOT THAT HAS USUALLY FORMED SOMEWHERE ELSE LIKE THE HEART, BROKEN FREE AND MOVED TO THE BRAIN AS AN EMBOLUS. LACUNAR: REDUCED PERFUSION: BRAIN CAVITIES RESULTING FROM DECREASED PERFUSION IN SMALL, DEEP VESSELS. OCCUR WITH SEVERE STENOSIS (GREATER THAN 70% NARROWING) OF THE CAROTID AND BASILAR ARTERIES AND WITH STENOSIS OF SMALL ARTERIES DEEP IN THE BRAIN. THROMBOTIC STROKE: ABNORMAL REGULATIONS OF HEMOSTATIC FACTORS, SUCH AS ANTICLOTTING PROTEINS, AND OF THE FIBRINOLYTIC SYSTEM THAT CAN OCCUR AT ANY AGE. P-129 FIBRINOLYSIS IS A PROCESS THAT PREVENTS BLOOD CLOTS FROM GROWING AND BECOMING PROBLEMATIC. [1] THIS PROCESS HAS TWO TYPES: PRIMARY FIBRINOLYSIS AND SECONDARY FIBRINOLYSIS. THE PRIMARY TYPE IS A NORMAL BODY PROCESS, WHEREAS SECONDARY FIBRINOLYSIS IS THE BREAKDOWN OF CLOTS DUE TO A MEDICINE, A MEDICAL DISORDER, OR SOME OTHER CAUSE.BLOOD CLOTS [1]

7. PHYSICAL ACTIVITY AND STROKE RISK: THE EVIDENCE PHYSICALLY ACTIVE MEN AND WOMEN GENERALLY HAVE A LOWER RISK OF STROKE INCIDENCE OR MORTALITY THAN DO THE LEAST ACTIVE—WITH MORE ACTIVE PERSONS DEMONSTRATING A 25% TO 30% LOWER RISK FOR ALL STROKES. STUDIES: P-130-135. PERIPHERAL ARTERY DISEASE (PAD): IS THE OBSTRUCTION OF BLOOD FLOW IN ARTERIES OTHER THAN THOSE TO THE HEART OR BRAIN, USUALLY BECAUSE OF ATHEROSCLEROSIS. THERE IS EVIDENCE THAT PAD IS A STROKE RISK FACTOR. STRENGTH OF EVIDENCE: P-136.

8. PERIPHERAL ARTERY DISEASE PAD IS THE OBSTRUCTION OF BLOOD FLOW IN ARTERIES OTHER THAN THOSE IN THE HEART OR BRAIN, USUALLY BECAUSE OF ATHEROSCLEROSIS. ABOUT 10% TO 30% OF ADULTS 55 AND OLDER HAVE PAD AND ABOUT HALF OF PEOPLE WITH PAD HAVE SYMPTOMS: INTERMITTENT CLAUDICATION (MUSCLE PAIN) DURING LEG EXERTION OR LEG PAIN WHILE RESTING. THERE IS EVIDENCE THAT PAD IS A RISK FACTOR FOR STROKE.

9. STRENGTH OF THE EVIDENCE TEMPORAL SEQUENCE: IV—PA; DV—STROKE. STUDIES SUGGEST THAT PA OFFERS A PROTECTIVE EFFECT AGAINST STROKE. STRENGTH OF ASSOCIATION: THE RISK REDUCTION IS IN THE RANGE OF 25%--30% FOR ISCHEMIC AND ALL STROKES. FINDINGS ON HEMORRHAGIC STROKE REDUCTION ARE LESS CLEAR, PROBABLY BECAUSE ITS INCIDENCE RATE IS LOWER THAN THAT OF ISCHEMIC STROKE. CONSISTENCY: NOT ALL STUDIES AGREE BUT MOST SHOW THE RISK IF ISCHEMIC STROKE LESS AMONG PA PEOPLE COMPARED TO SEDENTARY. DOSE RESPONSE: PERHAPS A THRESHOLD OR L-SHAPED EFFECT: A CERTAIN AMOUNT OF PA IS ASSOCIATED WITH PROTECTION AGAINST STROKE, BUT FURTHER INCREASES IN PA SHOW NO GREATER DECREASE IN RISK. PA DOES SEEM TO HELP THOUGH WHETHER THE INTENSITY IS MODERATE OR VIGOROUS. BIOLOGICAL PLAUSIBILITY: PA REDUCES THE RISK OF DEVELOPING ATHEROSCLEROSIS AND THROMBOSIS (ISCHEMIC STROKE). PA REDUCES CLOTTING RISK, REDUCES BLOOD LIPIDS, & INCREASES HDL AFTER A STROKE, REGULAR PA HELPS PROTECT AGAINST STROKE MORTALITY BY MITIGATING BRAIN CELL DAMAGE AFTER A STROKE.