stroke (CVA)

patient information sheets

Stroke Foundation Australia - stroke information in various languages - English, Arabic, Italian, Greek, Chinese and Vietnamese

epidemiology of stroke in Australia

48,000 Australians have a stroke each year, with 70% of these being their first ever stroke.
30% who have a stroke, have a further stroke within 1 year
~20% (9,000) die within 1 month of a stroke, and 1/3rd die within 12 months
78% of all deaths from stroke are in those aged 75yrs and older
incidence of stroke doubles for every decade after 45yrs age
stroke is the 3rd largest disease burden in Victoria & 2nd largest cause of years of life lost in women (4th largest in men)
whilst deaths from stroke and stroke incidence is decreasing, its prevalence is increasing with increased ageing population and increased survival after stroke.
in Victoria, acute stroke & TIA presentations are expected to increase at 2.7% p.a., while in the > 85yr old age group, it will rise by 5% p.a.
20% of ischaemic strokes in young adults is due to internal carotid artery dissection or vertebral artery dissection
20% of fatal strokes in those aged 15-44yrs is due to psycho-stimulant use, in particular, metamphetamine / meth / ice

risk factors

uncontrollable

advancing age
gender - more common in men
FH of stroke
- elevated lipoprotein A (Lp(a) ) levels appear to correlate with ischaemic stroke risk and general atherosclerosis risk in some studies although some other studies have not confirmed this ¹⁾
  - plasma level distribution in the general population is highly skewed (90% have serum values less than 300 mg/litre, median is around 80-90mg/L, some have levels above 20,000 mg/L)
  - exhibits a high degree of heritability through kringle isoform transmission
  - low MW isoforms tend to raise Lp(a) levels and correlate more with atherosclerosis and ischaemic stroke than high MW isoforms (almost half of stroke patients have low MW isoforms while only 16% have high MW isoforms)
  - Lp(a) are susceptible to oxidation and subsequent uptake into cells leading to cholesterol formation and foam cells
  - Lp(a) competes with plasminogen for its receptors on endothelial cells, leading to diminished plasmin formation, thereby delaying clot lysis and favouring thrombosis
  - Lp(a) levels rise as part of the acute phase response and also in hypothyroidism, DM, CRF, nephrotic syndrome, cancer, menopause, and with certain medications, possibly including statins (although only slightly)!
  - Lp(a) levels are reduced by hyperthyroidism, liver failure, oestrogens, progestogens, tamoxifen, anabolic steroids, high dose nicotinic acid and fibrates
  - diet does not appear to substantially alter Lp(a) levels
high homocysteine levels
high fibrinogen levels
PH miscarriage increases risk by 11% higher risk of a non-fatal stroke and 17% higher risk of a fatal stroke, and risk increases with number of miscarriages - those who had three or more miscarriages had a 35% higher risk for non-fatal stroke - presumably due to factors that may have contributed to miscarriage ²⁾
PH stillbirth - women who had a history of stillbirth had a 31% higher risk of non-fatal strokes (from an incidence rate of 42 per 100,000 person years to 69.5 per 100,000) and a 7% higher risk of fatal strokes, and the greater the number of stillbirths, the higher the risk of later strokes, with women who had had two or more stillbirths having a 26% higher risk of fatal strokes (rising from 11 per 100,000 person years to 51.1 per 100,000)³⁾

medical conditions contributing risk

PH TIA
atrial fibrillation
diabetes mellitus
hypertension
- hypertensive disorders of pregnancy (HDP)
  - having a hypertensive disorder of pregnancy doubles the risk of heart attack and stroke in later life
  - most mothers with a history of HDP are at moderate risk of long-term CVD death, a third are not at increased risk, and only a very small number are at high risk - those with a rare pattern of more than one hypertensive disorder in their reproductive history, and delivered their pregnancies early have a > 5x risk of stroke in later life ⁴⁾
fibromuscular dysplasia (FMD)
polycythaemia
thrombocytosis
surgery
- a 2019 Canadian study⁵⁾ suggests that 7% of those over 65yrs age having non-cardiac surgery have a covert stroke and 42% of these patients suffered cognitive decline by 1yr post-op compared with 29% of those who did not have a covert stroke
rare genetic causes of recurrent stroke:
- cerebral autosomal-recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)
  - recurrent lacunar strokes or progressive motor decline, cognitive function, alopecia, back pain with onset in the 20's
  - due to mutations in the HTRA1 gene

lifestyle modifiable risk factors

hypertension
hyperlipidaemia
- there is a correlation between ischaemic stroke and:
  - elevated total cholesterol
  - raised low density lipoprotein cholesterol (LDL)
  - raised TG levels
  - reduced HDL levels
  - high total cholesterol to HDL ratio
- there is a correlation between haemorrhagic stroke and:
  - very low total cholesterol concentrations
cease smoking
obesity and weight management - high BMI increases risk
diet
- low salt diet (for reducing hypertension)
- low saturated fats
- eating nuts (ideally should be unsalted, raw fresh nuts) two or more times per week was associated with a 17% lower risk of cardiovascular mortality compared to consuming nuts once every two weeks according to a 2019 Iranian study ⁶⁾
  - “Nuts should be fresh because unsaturated fats can become oxidised in stale nuts, making them harmful. You can tell if nuts are rancid by their paint-like smell and bitter or sour taste”
- high blood levels of the artificial sweetener erythritol (this is commonly used in Zero sugar drinks) appears to double risk of stroke and heart attacks ⁷⁾
lack of exercise increases risk
alcohol > 6 drinks per day appears to have increased risk
timing of meals:
- eating dinner meals after 8pm seems to increase stroke/TIA risk by 28% in woman compared to eating dinner before 8pm according to 2023 French study published in Dec 2023 ⁸⁾
  - each additional hour of nighttime fasting was associated with a 7% lower risk of cerebrovascular disease (HR = 0.93, 95% CI, 0.87–0.99, P-value = 0.02), but not with risk of overall CVD or coronary heart disease
  - no link between the daily number of eating occasions and the risk of overall CVD
see cardiovascular disease risk factor calculator

primary prevention

control risk factors: (see also atherosclerosis and primary prevention )
- hypertension
  - The UK TIA study concluded the variability in the systolic blood pressure was a strong predictor of stroke. The combination of calcium channel blockers and non-loop diuretics were associated with greatest reductions in systolic BP ⁹⁾
  - combined therapy with an ACEI and non-loop diuretic can reduce vascular events by 40% in 4 years with a mean reduction of blood pressure by 12/5 mmHg ¹⁰⁾
- smoking
- diabetes
- hyperlipidaemia
  - statins appear to reduce risk of stroke by 20-30%
  - in patients raised TG levels, fibrates appear to reduce stroke by ~25% and reduced TIAs by ~50% ¹¹⁾
- obesity and weight management
- high plasma fibrinogen
- excessive alcohol intake
- polycythaemia
- combined oral contraceptive pill (OCP)
- life long anticoagulant Rx for those with rheumatic or prosthetic heart valves on left side
- consider anticoagulation in pts with chronic AF
  - see antithrombotic Rx for prevention of stroke
  - no advantage of strict rate control (HR < 80) vs “lenient” rate control of HR < 110 in patients with AF for prevention of stroke, but strict rate control still advocated for those with recurrent symptoms or tachycardia cardiomyopathy ¹²⁾
  - AV nodal ablation rate has a low complication rate regardless of co-morbidity and should be considered for all patients with AF undergoing cardiac resynchronisation treatment and also to those who have rapid ventricular response despite medical therapy and are at risk of drug induced complications. ¹³⁾
- consider anticoagulation in pts with mural thrombus post acute myocardial infarction (AMI/STEMI/NSTEMI)
- consider aspirin 75mg/day if benefits outweigh risks:
  - eg. women aged 55 to 79 yrs if benefit outweighs risk of GIT haemorrhage¹⁴⁾

secondary prevention

see Mx of TIA

pathophysiology

ischaemic reperfusion injury
- 2024: discovery of a new bicarbonate-sensing receptor that regulates ischemic reperfusion injury
  - the Gpr30 G protein-coupled receptor (GPCR) is highly expressed in brain microvasculature (esp. in pericytes, cells that help maintain homeostatic and hemostatic functions in the brain) and is activated by higher levels of extracellular bicarbonate
  - GPR30 is also a G protein-coupled oestrogen receptor (GPER) that mediates the rapid non-genomic action of oestradiol (E2)
  - GPR30-deficient mice exhibiting significant protection against ischemic reperfusion injury, showcasing reduced neurological deficits, blood-brain barrier disruption, and apoptotic cell death and led to improved blood flow recovery after ischemia-reperfusion injury, emphasizing its role in controlling blood flow in both large vessels and capillaries.¹⁵⁾