ISCHEMIC STROKE / PREVENTION

Vascular risk factors

Created 26/03/2021, last revision 18/09/2022

Vascular risk factors
Non-modifiable risk factors
(cannot be changed)
  • previous stroke
  • person’s age
    • older people are at greater risk of developing cardiovascular disease. A healthy lifestyle is recommended to help reduce the risk
  • race
    • people of South Asian, African, or Caribbean descent have a greater risk of developing cardiovascular disease
  • male sex
  • family history

    • person’s first-degree relative developed CVD at a relatively young age (father/brother developed CVD before the age of 55, or mother/sister developed CVD before the age of 65)
    • a family history of hypertension, high cholesterol, and type 2 diabetes can also increase one’s chances of developing these conditions, which can, in turn, increase the risk of cardiovascular disease
Modifiable risk factors
(can be reduced or controlled with altered behavior)
  • hypertension
  • dyslipidemia (high levels of fats in the blood, such as cholesterol and triglycerides)
  • diabetes
  • heart diseases
    • atrial flutter and fibrillation
    • thrombus in the left atrium or ventricle
    • valvular defects
    • spontaneous echo contrast
    • AS plaques and thrombi in the ascendant aorta
  • cerebrovascular occlusive disease
  • smoking
  • hematologic disorders
  • overweight/obesity
  • lack of exercise
  • hyperhomocysteinemia
  • stress
  • drug abuse
  • alcoholism
  • hormonal contraception
  • migraine
  • inflammatory markers
    • C-reactive protein (CRP)
    • erythrocyte sedimentation rate (ESR)
    • fibrinogen, ferritin, and some other acute-phase proteins
  • sleep disorders (sleep apnea syndrome – SAS)

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Vascular risk factors

↓

Subclinical damage
endothelial dysfunction, enlarged IMT, increased arterial stiffness, myocardial hypertrophy, vascular hypertrophy, microalbuminuria

↓

Manifest cardiovascular diseases (CVD)
stroke/TIA, coronary artery disease (CAD), peripheral artery disease (PAD), aneurysm

Progression of atherosclerosis

Cardiovascular risk

The overall cardiovascular risk depends on:

  • risk factors control → ASCVD Risk Estimator Plus
    • a value of > 5% is considered as high risk (probability of death from cardiovascular disease in the next 10 years > 5%)
  • subclinical damage of target organs
  • clinical manifestation of CVD
    • people with overt CVD or renal disease have a high (> 5%) or very high (> 10%) risk of vascular death in the next 10 years
    • type 1 diabetes (T1D) with microalbuminuria and type 2 diabetes (T2D) have a high cardiovascular risk (> 5%)

Ankle-brachial pressure index (ABPI)

  • the ankle-brachial pressure index (ABPI) is a quick, non-invasive way to check peripheral artery disease (PAD)
    • the disease occurs when narrowed arteries reduce the blood flow to the limbs
    • abnormal ABPI may be an independent predictor of mortality, as it reflects the burden of atherosclerosis
  • it is a ratio of the blood pressure at the ankle to the blood pressure in the upper arm (brachial BP)
    • the patient must be in a supine position, without the head or any extremities dangling over the edge of the table
    • brachial BP is measured on both arms, and a higher value is used
  • a low ABPI index indicates narrowing or occlusion of peripheral arteries in the legs

   ankle BP

ABPI = ———————————

brachial BP

Interpretation of ABPI
> 1.3 abnormal  (vessel hardening from calcifications)
1-1.2 normal
0.9-0.99
 acceptable
0.8-0.89 mild PAD
 0.8 – 0.5 moderate PAD
< 0.5 severe PAD

Intima-media thickness (IMT)

  • the standard measurement is performed in B-mode on the far wall of CCA, 10 mm proximal from the bifurcation
    • use high-resolution images
    • optimize the angle of insonation (90° to the vessel wall)
  • distance of 2 echogenic lines is measured
    • the 1st line is the lumen-intima interface
    • the 2nd line is the media-adventitia interface
  • get at least five measurements on each side and get an average value (“average IMT”); specialized software can be helpful  Automated IMT measurement (GE LOGIQ) [Baldassare, 2000]
  • avoid atherosclerotic plaques when measuring IMT (lesions > 1.5 mm are already evaluated as plaque)
  • echogenicity, especially of the media, can increase in the presence of fatty infiltration and thickening
  • IMT > 95th. percentile for age and sex is taken as abnormal (usually IMT >1 mm is abnormal)
Intima-media thickness (ultrasound image)
Intima-media thickness (IMT) on ultrasound imaging
Female (P95)
 Male (P95)
45 y
 55 y
 65 y
 45 y 55 y
 65 y
0.73
 0.91 1.04
0.89
 1 1.3

95.th percentile  [Howard, 1993]

Age
 P25 P50
 P75
Men <30 0.39 0.43 0.48
Men 31-40  0.42 0.46 0.50
Men 41-50 0.46 0.50 0.57
Men >50  0.46 0.52 0.62
Women <30 0.39 0.40 0.43
Women 31-40 0.42 0.45 0.49
Women 41-50 0.44 0.48 0.53
Women >50 0.50 0.54 0.59

Prognostic value of IMT measurement

  • not only atherosclerotic plaques, but IMT as well can quantify atherosclerosis burden in asymptomatic patients
  • IMT should be assessed in each extracranial ultrasound exam
    • an increase in the intima-media thickness is the first stage of atherosclerosis, and if untreated, it is followed by plaque formation
    • clinical and epidemiologic studies showed an association of IMT with coronary artery disease (CAD), stroke, and peripheral vascular disease (PAD) (ROTTERDAM, ACAPS trials ) [Lorenz, 2007]
    • thickening of IMT correlates with the occurrence of traditional vascular risk factors (BMI, hypertension, hypercholesterolemia, diabetes, smoking)
    • some authors recommend including IMT and the AS plaques presence among the classic vascular risk factors [Chambless, 2010]
    • some publications question the importance of IMT in the CV events predictions [Costanzo, 2010] [Ruijter, 2012]
  • detection of subclinical atherosclerosis is important in patients with borderline risk and multiple risk factors, as it moves the patient to the high-risk category (≥ 5% by SCORE) with all therapeutic consequences
  • pharmacological studies have shown a reduction in the rate of progression of IMT on hypolipidemic therapy and antihypertensives (ACAPS, METEOR)
    • rosuvastatin did not induce disease regression
  • on the other hand, a meta-analysis of 41 randomized trials showed regression of cardiovascular events on hypolipidemic drugs but did not show a relationship between a decrease in CV events and regression of the IMT [Costanzo, 2010]
  • an increase in IMT can also be found in non-atherosclerotic diseases (e.g., Takayasu arteritis)

I. Risk factors used to stratify CV risk according to ASCVD Risk Estimator Plus

  • sex
  • race
  • blood pressure
  • total cholesterol, LDL, HDL
  • history of diabetes and smoking
  • therapy (antithrombotic therapy, statins, antihypertensive drugs)

II. Target organs subclinical damage

  • left ventricular hypertrophy
  • sonographically proven thickening of the arterial wall (carotid IMT ≥ 0.9 mm) or the presence of atherosclerotic plaques (atherosclerosis)
  • ankle-brachial pressure index (ABPI) ratio < 0.9
  • slight increase in serum creatinine (115-133 μmol / l)
  • microalbuminuria (30-300 mg / 24hrs)
  • ↓ glomerular filtration rate (< 60ml / min / 1.73 m3)

III. Clinical manifestation

  • cerebrovascular disease
  • heart disease
    • myocardial infarction
    • angina pectoris
    • chronic congestive heart failure (CHF)
  • aneurysms
    • a serious complication that can occur anywhere in your body
    • besides sudden life-threatening rupture, a slow leak is possible. If a blood clot within an aneurysm dislodges, it may block an artery ostium and cause hypoperfusion
  • renal impairment
    • diabetic/non-diabetic nephropathy
    • decrease in renal function (serum creatinine > 133 μmol/L)
  • peripheral vascular disease (PAD)
  • advanced retinopathy
    • with hemorrhage or exudates
    • papilledema (optic disc swelling)
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