Stroke (Apoplexy): Prevention

To prevent apolex (stroke), attention must be paid to reducing individual risk factors.Behavioral Risk Factors

  • Diet
    • Studies show that 10 g salt/day increases the risk of stroke by 23%. This amount corresponds to the usual consumption of table salt in Western countries.
    • Red and processed meat (defined as over 50 g/day), but less whole grains, fruits and vegetables, nuts and seeds, also less cheese and dairy products → ischemic apoplexy.
    • Consumption of eggs: risk of hemorrhagic apoplexy increased by a factor of 1.25 per 20 g/day
    • Increased cholesterol levels due to increased intake of saturated fatty acids (animal fats, contained in sausage, meat, cheese). Instead, mainly polyunsaturated fatty acids from vegetable fats as well as fish should be consumed. Studies show that the predominant use of olive oil and regular consumption of nuts is associated with a low rate of stroke.
    • High intake of highly sugary foods (eg, sweets, sweet drinks) – this increases blood glucose levels in the long term, which is damaging to blood vessels.
    • High intake of sweet drinks, especially if they are mixed with artificial sweeteners.
    • Low intake of whole grain products; fiber intake is inversely associated with apoplexy incidence, i.e., the lower the fiber intake, the higher the risk of stroke
    • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
  • Consumption of stimulants
    • Tobacco (smoking, passive smoking; (1.67-fold risk).
    • Alcohol
      • 1-2 alcoholic drinks/day (day) reduced risk of ischemic stroke; ≥ 3 drinks/day resulted in an increase in intracerebral hemorrhage and subarachnoid hemorrhage
        • Maximum of one drink per day: 9% risk reduction for ischemic stroke (relative risk RR 0.90; 95% confidence interval 0.85-0.95)
        • 1-2 drinks/die: 8% risk reduction (RR 0.92; 0.87-0.97).
        • 3-4 drinks/day: 8% increase in risk of ischemic stroke (RR 1.08; 1.01-1.15)
        • >4 drinks/day: 14% increase in risk of ischemic stroke (RR 1.14; 1.02-1.28) and 67% increase in intracerebral hemorrhage (RR 1.67; 1.25-2.23) and 82% increase in subarachnoid hemorrhage (1.82; 1.18-2.82)

        A new evaluation, which included data from 160,000 adults, contradicts this. The evaluation used the method of Mendelian randomization: it measured two genetic variants (rs671 and rs1229984) in the 160,000 adults that significantly reduce alcohol consumption. These genetic variants lead to a 50-fold difference in average alcohol consumption, from nearly 0 to about 4 drinks per day. Similarly, the genetic variants that reduced alcohol consumption also lead to a reduction in blood pressure and stroke risk. As a result, the authors showed that alcohol increases the risk of stroke by about one-third (35%) for every 4 additional drinks per day, with no preventive effect from light or moderate alcohol consumption.

      • Linear relationship between the level of alcohol consumption and the risk of apoplexy; for men who consume more than 21 drinks per month, the risk of apoplexy increases by 22% (= a glass of wine every day is already too much).
      • 2.09-fold risk of high or heavy episodic drinking versus never or former drinkers.
  • Drug use
    • Cannabis (hashish and marijuana)
      • There is evidence for a causal relationship between cannabis (hashish and marijuana) and cerebrovascular events.
      • Neither cumulative lifetime marijuana use nor more recent use of marijuana was associated with the occurrence of cardiovascular disease (CVD), apoplexy, or transient ischemic attack (TIA; sudden circulatory disturbance of the brain leading to neurologic dysfunction that resolves within 24 hours) in middle age.
      • Taking into account possible cofactors such as tobacco smoking, e-cigarette use, and alcohol consumption, the risk of stroke was shown to be increased with an odds ratio of 1.82 (95% confidence interval 1.08 to 3.10) for cannabis use overall and 2.45 (1.31 to 4.60) for individuals who used cannabis more than 10 days per month.
    • Heroin
    • Cocaine and amphetamines/methamphetamine (“crystal meth”) are a common cause of stroke. Particularly in the 18- to 44-year-old age group, one in seven strokes is caused by drug use. Amphetamines and cocaine can abruptly increase blood pressure. Cocaine can also cause vasospasm, while amphetamines cause cerebral hemorrhage. A U.S. study found that amphetamine users have a 5-fold increased risk of brain hemorrhage, called hemorrhagic stroke. The other form is ischemic stroke, triggered by a sudden disturbance of blood flow in the brain. As a result, brain cells die within a few minutes. According to the US study, cocaine doubled the risk of both ischemic and hemorrhagic stroke.
    • Opiates
  • Physical activity
    • Men can reduce the risk of cerebral infarction by 27% and the risk of cerebral hemorrhage by 40% through physical activity; there are no significant preventive effects in women
    • Walking two hours a day appears to reduce the risk of apoplexy by nearly one-third in older people
  • Psycho-social situation (2.2-fold risk).
    • Chronic stress
    • Lonely and socially isolated people (+39%).
    • Hostility
    • Anger attack (trigger; in the first two hours, the risk of apoplexy increases by a factor of 3)
    • Work stress (category: high demands, low level of control); women 33%, men 26% higher risk of apoplexy.
    • Long working hours (> 55 h / week).
    • Loneliness and social isolation (32% increased risk (pooled relative risk 1.32; 1.04 to 1.68).
  • Sleep duration
    • Sleep duration 9-10 hours – In a large-scale study, it was observed that people who slept 9-10 hours were 10% more likely to suffer cardiovascular events such as apoplexy (stroke) than those who slept 6-8 hours. If the sleep duration was more than 10 hours, the risk increased to 28%.
  • Overweight (BMI ≥ 25; obesity).
    • Increases the risk for apoplexy
    • Increased risk esp. for cerebral infarction
    • Above-average body mass index at age 7-13 years increases the risk of apoplexy
      • Girls: when the average BMI was exceeded by one standard deviation (corresponding to a weight gain of 6.8 kg), this increased the risk of stroke by 26% by age 55; when the BMI was two standard deviations above the average (16.4 kg of additional weight), the risk increased by 76%
      • Boys: one BMI standard deviation more (5.9 kg weight) = 21% increase in risk of early insult; two standard deviations (14.8 kg) increase of 58

    Note: In biobank studies with so-called Mendelian randomization, no significance was demonstrated for the phenotypically defined cohort “apoplexy” with respect to obesity. Significance for risks associated with increased BMI resulted with full adjustment for arterial hypertension / hypertension (65%) and diabetes mellitus type 2 153%).

  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type) – high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)) is present; 1.44-fold risk When waist circumference is measured according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
    • Men <94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

  • Abdominal obesity is known to be associated with an increased risk of ischemic cerebral infarction. Mendelian randomization was used to examine the effects of waist-hip index (THI)-as an indicator of abdominal obesity-on the mediators systolic blood pressure and fasting glucose. The study showed:
    • 12% of the effect that THI exerted on insult risk was attributable to systolic blood pressure.
    • Fasting glucose and HBA1c levels did not contribute to the THI effect.

    Abdominal obesity increases the risk of stroke largely independent of systolic blood pressure and glucose levels.CONCLUSION: Abdominal obesity independently triggers pathological (pathological) processes (eg, inflammatory processes, increased coagulation, and impaired fibrinolysis/dissolution of a fibrin clot by enzyme action) that can cause apoplexy.

Laboratory diagnoses-laboratory parameters considered independent risk factors.

  • Apolipoprotein (Apo)B/ApoA1 quotient (1.84-fold risk).
  • C-reactive protein (CRP)
  • Erythrocytosis – increased number of red blood cells.
  • Glomerular filtration rate (GFR)
  • Homocysteine levels – Elevated homocysteine levels are associated with an increased risk of ischemic and recurrent apoplexy; however, there is no clear association with hemorrhagic apoplexy.
  • Hyperlipoproteinemias (dyslipidemia):
    • Hypercholesterolemia
    • Hypertriglyceridemia (in men with nonfasting triglyceride levels of 89-176 mg/dl, the risk of apoplexy is already increased by 30%, and by as much as 2.5-fold for levels above 443 mg/dl, compared with men with triglyceride levels below 89 mg/dl. In women, the risk increased even up to 3.8 times at very high triglyceride levels compared to low triglyceride levels).
    • Total cholesterol
  • Fasting glucose (fasting blood sugar)
    • Prediabetes as defined by the American Diabetes Association: 100-125 mg/dl (5.6-6.9 mmol/l) (1.06-fold risk)
    • Prediabetes as defined by the WHO: 110-125 mg/dl (6.1-6.9 mmol/l) (1.20-fold risk)

Medication

  • Alpha blockers
    • In the first 21 days after the first prescription of alfuzosin, doxazosin, tamsulosin, or terazosin, there was a 40 percent increase in ischemic strokes
    • Patients concomitantly taking another antihypertensive (medication to lower blood pressure) in addition to an alpha blocker had no increased risk of apoplexy in the postexposure 1 period ( ≤ 21 days thereafter), and the incidence in the postexposure 2 period (22-60 days thereafter) decreased even further (IRR 0.67)
    • ALLHAT trial: doxazosin (alpha blocker) patients had a higher risk of stroke and combined cardiovascular disease than chlorthalidone patients. The risk of CHD was doubled.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, diclofenac) including COX-2 inhibitors (synonyms: COX-2 inhibitors; commonly: coxibs; e.g. Celecoxib, etoricoxib, parecoxib) – increased risk with current use of rofecoxib and diclofenac; increased risk of ischemic infarction with use of diclofenac and aceclofenac up to 30 days before the event.
  • Aceclofenac, similar to diclofenac and the selective COX-2 inhibitors, is associated with an increased risk of arterial thrombotic events.
  • Use of new-generation oral contraceptives (birth control pills) are associated with an increased risk of first-time cerebral infarction. Hormonal contraceptives with lower estrogen concentrations had a lower risk of cerebral infarction compared with those with normal estrogen concentrations.All four generations of progestins have been associated with an increased risk of ischemic stroke. The risk of ischemic stroke appeared to be slightly lower among fourth-generation users than among those on the previous generations of progestins.
  • Regadenoson (selective coronary vasodilator), which may be used for diagnostic purposes only (stress trigger for myocardial perfusion imaging; myocardial perfusion imaging, MPI), increases risk of apoplexy; contraindications: history of atrial fibrillation or existing risk of severe hypotension (low blood pressure); caveat. Aminophylline is not recommended for termination of regadenoson-related seizures!
  • Recombinant growth hormone (STH) therapy in children – Factor 3.5 to 7.0 increased incidence rate of hemorrhagic stroke; Factor 5.7 to 9.3 increased rate of subarachnoid hemorrhage.

Environmental exposure – intoxications (poisonings).

  • Noise
    • Compared with road noise <55 db, road noise >60 db increases the risk of apoplexy by a significant 5% in adults and by a significant 9% in those aged 75 years and older
    • Aircraft noise: increase in average noise level by 10 decibels increases stroke risk by 1.3
  • Air pollutants
    • Particulate matter due to environment, household (due to coal stove and stove).
    • Smog (particulate matter, nitrogen dioxide, sulfur dioxide).
  • Weather
    • Temperature drops (risk increase; risk remains elevated for 2 more days; temperature drop of about 3°C each increases risk of apoplexy by 11%)
    • Rapid change in humidity as well as atmospheric pressure.
  • Heavy metals (arsenic, cadmium, lead, copper).

Prevention factors (protective factors)

  • Man and woman:
    • ‘Healthy lifestyle’; criteria:
      • Five times a week a meal with fruits and vegetables.
      • <30 grams of meat products per day
      • A handful of nuts daily
      • Predominant use of olive oil
      • Nicotine restriction (refrain from tobacco use).
      • Limited alcohol consumption (men and women: max. 30 g alcohol per day).
      • At least 150 minutes of physical activity per week
      • BMI (body mass index; body mass index): 18.5-25 kg/m2.

      According to one study, this “healthy lifestyle” results in a 72% reduction in the risk of stroke (relative risk [RR]: 0.28; 95% confidence interval between 0.14 and 0.55; p < 0.0001). The reduction in ischemic (RR: 0.31) and hemorrhagic insults (RR: 0.29) was similar.The global INTERSTROKE trial assumes a 60% risk reduction.

    • Stroke risk was 35% higher in those at high genetic risk than in those at low genetic risk, regardless of lifestyle. In the same study, unfavorable lifestyle was associated with a 66% increased risk of stroke compared with favorable lifestyle. Adherence to four factors reduced stroke risk by 66%:
      • Not smoking
      • Diet rich in fruits, vegetables and fish
      • Body mass index below 30 (ie not overweight or obese).
      • Regular physical exercise
    • Egg consumption: daily egg consumption (0.76 eggs/day) reduced the risk of hemorrhagic stroke by 26%; the risk of ischemic heart disease decreased by 12%.
    • Nicotine restriction; most important risk factor.
    • Coffee consumption (one to three cups of coffee per day have a preventive effect).
    • Sporting activities
      • 0.4 times the risk
      • 1 to 3 times per week; the important thing is that the exercise is intense enough to make you sweat.
    • Frequent full baths (here: hot bath; Japanese bath, Japanese hot bath; bath water temperature: normal 40-42 °C, often even 43 °C): A daily or almost daily hot full bath reduced the overall risk of subsequent cardiovascular disease by a significant 28% compared with bathers (no full bath or at most twice a week). Apoplexes (strokes) why by 26% less frequently and cerebral hemorrhages by 46%; no effect had the frequent full baths on the frequency of myocardial infarction (heart attack) or coronary heart disease (CHD; coronary artery disease). Bathing frequency and sudden cardiac death (PHT) were not associated.
    • Blood pressure monitoring (blood pressure self-monitoring) [Class IA recommendation pronounced (highest evidence, best risk-benefit ratio) 23]
    • U.S. Preventive Services Task Force (USPSTF) advocates ASA use for men and women for primary prevention:
      • Between 50 and 59 years of age with a life expectancy of at least 10 years whose estimated risk of having a myocardial infarction or apoplexy (stroke) in the next 10 years is >10%; there should be no increased risk of bleeding; and patients should be willing to take ASA for at least 10 years (B recommendation)
      • Between 60 and 69 years of age with an appropriate profile, this recommendation is optional and should be made on an individual basis (C recommendation)
    • Atrial fibrillation (VHF): therapy with oral anticoagulants in addition to vitamin K antagonist (VKA) in the case of non-valvular (non-valvular) atrial fibrillation, a high risk of apoplexy (CHA2DS2-VASc value of at least 2), and an acceptable risk of patient bleeding (for more information, see Apoplexy/Medical Therapy); in the case of valvular atrial fibrillation and/or a high risk of apoplexy with a vitamin K antagonist.
    • Anticoagulation in asymptomatic patients with severe mitral stenosis and abnormalities such as an enlarged left atrium, and also after ST-elevation myocardial infarction (STEMI).
    • Asymptomatic carotid stenosis (narrowing of the vessels supplying the brain): acetylsalicylic acid (ASA)) and statins (cholesterol-lowering drugs).
    • Acetylsalicylic acid (ASA).
      • ASA use reduced the incidence of stroke (fatal or not) to 5.3 events per 1,000 patient-years in the control groups to 4.7 per 1,000 in the ASA groups; however, study participants had a 41% increased risk of bleeding: per 1. 000 patient-years, 2.5 major – gastrointestinal (gastrointestinal-related), intracranial (” inside the skull“), or other – bleeding events (major bleeding) occurred, compared with 1.8 per 1,000 without ASA.
      • Acetylsalicylic acid–clopidogrel combination therapy appears to reduce the rate of major ischemic events, especially during the first 30 days, whereas major bleeding occurred more frequently after 1 week.
    • Statins for elevated LDL cholesterol → reduction of ischemic insults/thrombosis or embolism to cerebral artery occlusion (risk ratio (RR) was 0.70).
    • Influenza vaccination: vaccinated individuals have an 18 percent lower risk of stroke than unvaccinated individuals (OR 0.82).
  • Woman:
    • Smokers who suffer from migraine with aura should quit smoking, as both factors increase the risk of apoplexy.
    • Pregnancy:
      • Women with a history of hypertension during pregnancy and pregnant women with primary or secondary hypertension (high blood pressure): from the twelfth week of gestation (week of pregnancy) until delivery, intake of 75-150 mg/d acetylsalicylic acid (ASA).
      • Slightly to moderately elevated blood pressure (150-159/100-109 can be treated antihypertensively (blood pressure-lowering drugs); blood pressure above 160/110 mmHg must be treated antihypertensively in any case
      • To prevent preeclampsia (occurrence of hypertension and proteinuria/increased excretion of protein with urine) during pregnancy), calcium supplementation (at least 1 g/d) is recommended in pregnant women with low calcium intake (below 600 mg p/d)
    • Medications:

Secondary prevention

  • Telemedical monitoring using an outpatient implanted bio-monitor: daily data transmission makes atrial fibrillation detectable at any time. This reduces the number of new strokes by timely intervention.
  • Pioglitazone reduced the rate of recurrent stroke or myocardial infarction (heart attack) in a large placebo-controlled study in insulin-resistant patients after apoplexy or TIA (transitory ischemic attack; sudden circulatory disturbance of the brain leading to neurological disturbances that resolve within 24 hours). It simultaneously led to an increased rate of fractures (broken bones) and weight gain. Notice: Pioglitazone has also been shown in numerous studies to increase the incidence of cardiac decompensation (“heart failure“). It is contraindicated in patients with heart failure/heart failure (NYHA I-IV).
  • Intensive blood pressure reduction: target values 120/80; according to a meta-analysis, the relative risk of another stroke decreases by 22 percent; absolute reduction in risk by 1.5 percentage points (i.e., out of 67 patients, one is saved from another apoplexy).
  • A reanalysis of previous randomized clinical trials in the Lancet showed that early initiation of acetylsalicylic acid (ASA) therapy in patients with transient ischemic attack (TIA) or apoplexy (stroke) may be the most effective secondary prevention measure. Here to the results of a study confirming this:
    • 2 of 6,691 patients (0.03 percent) treated with ASA immediately after TIA suffered another major stroke in the next two weeks; control group: 23 of 5,726 patients (0.4 percent)
    • Early initiation of acetylsalicylic acid (ASA) therapy after apoplexy, ie, within the first six weeks, 84 of 8,452 (0.9 percent) of patients who received ASA suffered another ischemic apoplexy. Comparison group without ASA: 175 of 7,326 patients (2.3 percent).
  • The antiplatelet agent ticagrelor was no more effective than ASA for a combined vascular end point in the secondary prevention of apoplexy. However, ticagrelor significantly prevented ischemic insults more frequently.
  • If patients receive dual antiplatelet therapy (clopidogrel and aspirin) for secondary prevention of TIA/apoplex, this should be targeted only in the first 3 weeks after an ischemic event, and then switch to monotherapy. This leads to reduce the rate of severe ischemic events in the first 30 days, and at the same time takes into account that severe bleeding is more common after a week.
  • Statins for elevated LDL cholesterol → reduction of ischemic insults/thrombosis or embolism to occlude cerebral arteries (risk ratio (RR) was 0.80).