Overweight / obesity

  • obesity (defined as having over 30% of normal weight) is an independent risk factor for stroke
    • the central (abdominal) type of obesity is considered the riskiest
  • associated with other risk factors ( metabolic syndrome – hypertension, hyperglycemia, hyperlipidemia)
  • weight reduction is strongly recommended in:
    • obese individuals (BMI ≥ 30 kg/m2)
    • overweight individuals (BMI 25.0-29.9 kg/m2)
    • individuals with abdominal obesity (waist circumference > 102 cm in men and > 88 cm in women)
  • goals of therapy:
    • the initial goal in obese individuals is a 5-15% reduction in weight, which significantly reduces cardiovascular and metabolic risks
    • in cases of severe obesity, greater weight loss may be indicated
  • complex treatment of obesity consists of:
    • diet with a 15-30% reduction in energy content compared to the usual diet in a patient with stable weight; the reduction in energy is achieved mainly by restricting fats
      • a Mediterranean diet is recommended
    • lifestyle modifications
      • increasing moderate-intensity physical activity (e.g., brisk walking) for at least 30 min, 4-7 times a week
      • adequate sleep
    • pharmacotherapy
    • bariatric surgery should be considered for individuals with severe obesity (BMI 40 kg/m2, or 35-40 kg/m2 in selected cases)
  • regular monitoring of BMI is advised
  • the foundation of this diet is fiber, e.g., vegetables, fruits, nuts, fish, olive oil, light meats in small quantities, legumes, whole grains
  • sufficient drinking of unsweetened beverages
  • red wine may be consumed in limited quantities (1dcl per day)
  • underweight = BMI <18.5 kg/m2
  • normal weight =  BMI 18.5–24.9 kg/m2
  • overweight = BMI 25–29.9 kg/m2
  • obesity = BMI ≥ 30 kg/m2

Physical inactivity

  • regular physical activity reduces the risk of cardiovascular diseases (CVD) and is associated with several health benefits:
    • ↓ risks of stroke by up to 30%
    • reduction/prevention of obesity
    • beneficial effects on hypertension and heart rate (slowing)
    • decreased fibrinogen levels and platelet activation
    • increase in tPA, raised C-HDL, and decreased C-LDL levels
    • increased insulin sensitivity and improved glucose tolerance
  • lack of exercise conversely increases the risk of hypertension, DLP, or obesity
    • even non-overweight people with a lack of exercise have a higher risk of CVD
  • the most significant benefit in reducing stroke incidence (both ischemic and hemorrhagic) is derived from the most intense level of exercise
  • a minimum of 30 minutes of physical activity most days of the week is recommended; even moderate activity is associated with improved health
    • choose enjoyable forms of physical activity
    • ideally 30-45 minutes, 4-5 times a week, at 60-75% of the average maximum heart rate
    • individuals with sedentary jobs should do short exercises (about 3-5 minutes) every 30 minutes


  • negative emotional reactions and stress (e.g., work stress, socioeconomic disasters, interpersonal problems) lead to significant sympathetic activation → increased blood pressure and/or heart rate
  • stress thus promotes the development of hypertension, atherosclerosis, and CAD


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Oral contraceptives

  • oral contraceptives (OCs) and hormone replacement therapy (HRT) increase the risk of stroke and sinus venous thrombosis
  • the risk is further potentiated:
    • in patients with thrombophilia or a history of venous thromboembolism (VTE)
      • 13-fold increased risk in patients with the Leiden mutation
      • 9-fold increased risk in the presence of hyperhomocysteinemia
    • in the presence of coexisting risk factors (smoking, hypertension, obesity, and age > 35 years)
  • in non-smokers, the risk is low (~2/100,000/year) when using OCs containing <50ug of ethinyl estradiol [Carr, 1997]
Multifactorial prothrombogenic effect of OCs
  • ↑ clotting factors I, II, VII, VIII, X
  • ↓ factor V
    • highest with 3rd generation progestins
  • ↓ AT III and protein S
  • acquired resistance to activated protein C (APC)
  • ↓ TAFI levels (Thrombin-Activatable Fibrinolysis IAnhibitor)
  • the risk of stroke/MI depends mainly on the estrogen content and less on the type of progestin  [Lidegaard, 2012]
    • ethinyl estradiol
      • < 20 μg – relative risk 0.9-1.7
      • 30-40 μg – relative risk 1.3-2.3
    • progestins – relatively small differences in risk according to progestin type (RR from 1.7 to 2.2)
      • 2nd generation OCs containing levonorgestrel (RR 1.7)
      • 3rd generation with desogestrel (2.2) or gestodene (1.8)
  • according to some epidemiological studies, levonorgestrel appears safer than the 3rd generation progestins (desogestrel, gestodene, norgestimate) [Sidney, 2013], [Carr, 1997]
  • female smokers > 35 years of age should avoid combined estrogen-progesterone oral contraceptives (OC)
  • routine thrombophilia screening before contraceptive use is not recommended; however, a detailed personal and family history of thromboembolic complications should be obtained
    • in women with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE), thrombophilia screening is necessary before initiating OCs or HRT
  • intrauterine devices (IUDs) and estrogen-free implants (progestin-only) are the safest contraceptive options

    • particularly advisable for women with multiple CV risk factors (e.g., age  > 35 years, smoking, obesity, diabetes, hypertension, or migraines)


  • homocysteine (Hcy) is a non-essential amino acid produced during the metabolic conversion of methionine to cysteine
  • it is a degradation product that is broken down by 2 pathways
    • remethylation back to methionine, which requires the presence of folic acid (folate) and vitamin B12
    • transsulfuration to cysteine in the presence of the active form of vitamin B6; cysteine is then excreted via urine
  • hyperhomocysteinemia is a metabolic syndrome caused by the interaction of genetic and exogenous factors and is associated with several medical conditions:
    • genetic mutations in methylenetetrahydrofolate reductase (MTHFR), such as  677TT)
    • vitamin B6,12, folate deficiency
    • increased dietary intake of methionine due to excessive consumption of animal protein, coffee, and alcohol
    • Hcy levels increase with age and with the use of f certain anticonvulsants (CBZ, PHE)
  • hyperhomocysteinemia promotes premature atherosclerosis and thrombosis
    • the 677TT MTHFR genotype is associated with a 20% increased risk of venous thrombosis compared to the 677CC genotype
  • according to the 1998 NHANES III (National Health and Nutrition Examination Survey) trial, homocysteine is considered an independent stroke risk factor
  • homocysteine
    • men: 4-12 µmol/L
    • women: 4-10 µmol/L
  • folic acid:  > 7 nmol/L  (borderline deficit 5-6.9 nmol/L)  (Galukande, 2011)
  • vitamin B12: 150-520 pmol/L  (usually symptomatic when < 74 pmol/L)
  • vitamin B6 (pyridoxine):  39(18) – 98 nmol/L  (5-50 ug/L)

  These values may vary slightly depending on the laboratory and the specific assay used for measurement

  • Hcy levels can be reduced by folic acid (ACIDUM FOLICUM) and, to a lesser extent, by vitamins B12 and B6 (supplementation is important in C677T homozygotes)
    • ACIDUM FOLICUM 10 mg daily
    • PYRIDOXIN once a day
    • or  B12 injection of 1000 ug once a week (minimum of 5 injections) in cases of proven hypovitaminosis
  • supplementation reduces the level of Hcy in the serum
  • however, no statistically significant relationship was found between treatment-induced homocysteine reduction and a reduced risk of stroke (negative VITATOPS and VISP trials) (AHA/ASA 2021 III/B-R)
  • routine screening for hyperhomocysteinemia after TIA/stroke is not recommended (AHA/ASA 2018 III/C-EO)
  • diet and supplementation are recommended for confirmed cystathionine β-synthase (CBS) deficiency (homocystinuria) (AHA/ASA 2021 1/C-LD)
    • recommended dietary modifications include a diet low in methionine and rich in cysteine, pyridoxine, B12, and folate


  • chemotherapeutic drugs ⇒ ↑ risk of stroke/sinus thrombosis
    • tamoxifen, cisplatin, vinblastine, bleomycin, and others
  • ergotamine derivatives ⇒ ↑ incidence of sinus thrombosis with long-term use
  • NSAID – long-term can elevate blood pressure and increase the risk of stroke
  • tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been linked to a slightly increased risk of stroke (hemorrhagic), especially in elderly patients  (Trajkova, 2019)   (Khokhar, 2017)
  • immunosuppressants, such as cyclosporine and tacrolimus, may increase the risk of stroke due to their effects on blood pressure and lipid metabolism

Abuse of drugs

  • known association with stroke:
  • some drugs also increase the risk of bleeding (e.g., amphetamine)
  • the pathogenesis of vascular events is multifactorial:
    • a sudden increase in blood pressure
    • vasculitis
    • direct vascular toxicity
    • vasospasm
    • septic emboli
    • hemostatic and hematologic disorders, increasing blood viscosity and platelet aggregability


  • studies detected a higher risk of stroke associated with migraine with aura
  • concomitant smoking and oral contraceptive use increase the relative risk of stroke among women with migraine

Inflammatory markers

High-sensitivity C-reactive protein (hs-CRP)
  • CRP is a sensitive indicator of inflammatory response in the body; its synthesis in the liver is induced by cytokines (IL-6)
  • accurate detection of CRP concentrations in the range of 0-5 mg/L can be performed using a special high-sensitivity CRP test (hs-CRP)
  • even mildly elevated hs-CRP (> 3mg/L) represents a significant risk factor for atherosclerosis and its complications (stroke, CAD, etc.)  [Poledne, 2007]
  • inflammation is involved in the development of endothelial dysfunction, which is considered the initial stage of atherogenesis
  • hs-CRP <1 mg/L is considered a sign of low risk (values of 1-3 mg/L are of uncertain significance)
  • hs-CRP measurement is not recommended as a screening method
  • may be helpful in primary prevention for individuals at intermediate risk where it is uncertain whether and how aggressively to treat.
  • statins and weight loss are associated with central fat loss and have been found to reduce hs-CRP levels
  • better indicators of successful treatment and prevention of CVD are reductions in body weight, waist circumference, plasma lipid levels, and blood pressure

Sleep disorders

  • in particular, Sleep Apnea Syndrome (SAS), with a prevalence of ~ 10%, has been shown to increase the risk of stroke and/or death, independent of other vascular risk factors

Menopause and hormone replacement therapy (HRT)

  • hormone replacement therapy (HRT) does not reduce the risk of CV events (risk increases with age regardless of HRT usage)
  • HRT is not recommended to reduce the risk of stroke or ICH, nor is it recommended for postmenopausal women with a history of stroke (ESO guidelines 2022)
    • studies have shown that  women taking HRT face an increased risk of stroke, with a RR of 1.41 (Rossow, 2002)

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Other vascular risk factors
link: https://www.stroke-manual.com/other-vascular-risk-factors/