ISCHEMIC STROKE / PREVENTION

Vascular risk factors

David Goldemund M.D.
Updated on 11/04/2024, published on 26/06/2023

The early detection and management of cardiovascular risk factors is crucial for effective primary and secondary stroke prevention

Overview of cardiovascular risk factors

Vascular risk factors
Non-modifiable risk factors
(cannot be changed)
  • previous stroke
  • person’s age
    • older people have a higher 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 higher risk of developing cardiovascular disease
  • male sex
  • family history

    • having a first-degree relative who 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 high blood pressure, high cholesterol, and type 2 diabetes may also increase the likelihood of developing these conditions, which in turn may increase the risk of CVD
Modifiable risk factors
(can be reduced or controlled with lifestyle changes and medication)
  • arterial hypertension
  • dyslipidemia (high levels of fats in the blood, such as cholesterol and triglycerides)
  • diabetes
  • heart diseases
    • atrial flutter and fibrillation
    • left atrium or ventricle thrombus
    • valvular defects
    • spontaneous echo contrast
    • atherosclerotic plaques and thrombi in the ascending aorta/aortic arch  → aortic arch atherosclerosis
  • cerebrovascular occlusive disease
  • smoking
  • hematologic disorders
  • other risk factors
    • overweight/obesity
    • lack of physical activity
    • hyperhomocysteinemia
    • stress
    • drug abuse
    • alcohol abuse
    • hormonal contraception (OC)/hormone replacement therapy (HRT)
    • migraine
    • inflammation
      • markers: hs-CRP, IL-6, MCP-1, etc.
      • inflammation plays a crucial role in the development and progression of atherosclerosis
    • sleep disorders
      • sleep apnea syndrome – SAS

Progression of atherosclerosis

Cardiovascular risk

The overall cardiovascular risk depends on:

  • risk factors control → ASCVD Risk Estimator Plus
    • a value > 5% is considered high risk (probability of death from cardiovascular disease in the next 10 years)
  • subclinical target organ damage
  • clinical manifestations 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
    • individuals with 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 for peripheral artery disease (PAD)
    • the disease occurs when narrowed arteries reduce blood flow to the limbs
    • an 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 the supine position, without the head or any extremities dangling over the edge of the table
    • the brachial BP is measured in both arms, and the 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 due to 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)

  • decades of silent arterial wall alterations precede atherosclerotic disease with clinically evident cardiovascular events
  • the first detectable morphological abnormalities (enlargement of intima-media) can be visualized using B-mode imaging
  • the intima-media extends from the luminal edge of the artery to the boundary between the media and the adventitia
How to measure IMT?
  • the standard measurement is performed in B-mode on the far wall of the common carotid artery (CCA), 10 mm proximal to the bifurcation
    • use high-resolution images and adjust depth of focus and gain settings to obtain optimal image quality
    • employ linear ultrasound transducers at frequencies above 7 MHz
    • optimize the insonation angle (90° to the vessel wall)
    • values obtained from different sites (such as distal ICA, bulb) should be documented separately
    • values from the near wall are dependent on gain settings and are thus less reliable
  • measure the distance between the 2 parallel echogenic lines
    • the first line represents the lumen-intima interface
    • the seond line represents the media-adventitia interface
  • obtain at least five measurements on each side and calculate the average value (“average IMT”); specialized software may be helpful  Automated IMT measurement (GE LOGIQ) [Baldassare, 2000]
    • automated systems can rapidly provide the mean maximal value of 150 measurements performed over a 10 mm segment of the CCA
  • perform IMT measurements in a region free of atherosclerotic plaque, which is defined as:
    • lesion ≥1.5 mm
    • structure encroaching into the arterial lumen by at least 0.5 mm or 50% of the surrounding IMT value
  • interadventitial and lumen diameter must also be obtained, as IMT correlates with arterial diameter
  • echogenicity, especially of the media, may be increased in the presence of fatty infiltration and thickening
Carotid intima-media thickness (CIMT)
What is normal IMT?
  • IMT > 75-95th percentile for age and sex is considered abnormal
  • some authors suggest simple cut-off values:
    • IMT < 0.8 mm – value associated with normal healthy individuals
    • IMT ≥ 1 mm – value associated with atherosclerosis and a significantly increased risk of cardiovascular disease (CVD) in any age group
Intima-media thickness (IMT) on ultrasound imaging
Women (95. percentile)
 Men (95. percentile)
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

 (Simova, 2015)

Prognostic value of IMT measurement

  • not only atherosclerotic plaques but also IMT can quantify atherosclerosis burden in asymptomatic patients
  • IMT should be assessed in each extracranial ultrasound examination
    • increased IMT represents the first stage of atherosclerosis and, if left untreated, is followed by plaque formation
    • clinical and epidemiological studies have shown an association between IMT and coronary artery disease (CAD), stroke, and peripheral vascular disease (PAD) (ROTTERDAM, ACAPS trials ) [Lorenz, 2007]
    • thickening of IMT correlates with the presence of traditional vascular risk factors (high BMI, hypertension, hypercholesterolemia, diabetes, smoking)
    • some authors recommend including both IMT and the presence of atherosclerotic plaquess among the classic vascular risk factors [Chambless, 2010]
    • some publications question significance of IMT in predicting cardiovascular events [Costanzo, 2010] [Ruijter, 2012]
  • detection of subclinical atherosclerosis is important in patients with borderline risk and multiple risk factors, as it shifts the patient into the high-risk category (SCORE ≥ 5%) with all therapeutic consequences
  • pharmacological studies have shown a reduction in the rate of progression of IMT with hypolipidemic therapy and antihypertensive drugs (ACAPS, METEOR)
  • on the other hand, a meta-analysis of 41 randomized trials showed regression of cardiovascular events with hypolipidemic drugs but did not show a relationship between a decrease in CV events and a regression of IMT [Costanzo, 2010]
  • an enlarged arterial wall 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
  • lipids (total cholesterol, LDL-C, HDL-C)
  • history of diabetes and smoking
  • therapy (antithrombotics, lipid-lowering drugs, antihypertensives)

II. Target organs subclinical damage

  • left ventricular hypertrophy
  • sonographic evidence of sn enlarged carotid IMT or the presence of atherosclerotic plaques (atherosclerosis)
  • ankle-brachial pressure index (ABPI) ratio < 0.9
  • mild increase in serum creatinine (115-133 μmol/L)
  • microalbuminuria (30-300 mg/24h)
  • ↓ 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 develop anywhere in the body
    • besides sudden life-threatening rupture, slow leaks are also 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)
  • retinopathy
    • with hemorrhage or exudates

Risk stratification (ESC 2019)

ESC guidelines 2019

Very-high-risk
  •  documented ASCVD (either clinical or clear on imaging)
    • CAD
      • acute coronary syndrome (ACS) – MI or unstable angina
      • stable AP
      • coronary revascularization (PCI, CABG) or other arterial revascularization procedures
    • stroke/TIA
    • peripheral arterial disease (PAD)
    • significant atherosclerosis on carotid ultrasound, coronary CTA, etc.
  • diabetes with organ damage (proteinuria, retinopathy, polyneuropathy) or ≥ 3 major risk factors and/or T1DM with long duration (> 20 years)
  • severe CKD (eGFR: <30 mL/min/1.73 m2 (0.5 mL/s)
  • a calculated SCORE ≥ 10% for a 10-year risk of fatal CVD
  • FH + ASCVD or with another major risk factor
High-risk (elevated single risk factors)
  • total cholesterol > 8 mmol/L (> 310 mg/dL)
  • LDL-C >4.9 mmol/L (>190 mg/dL)
  • BP ≥  180/110 mmHg
  • patients with FH without other major risk factors
  • diabetes without organ damage with a duration ≥ 10 years or any other additional risk factor
  • moderate CKD – eGFR  30-59 mL/min/1.73 m2 ( 0.5-0.99 mL/s)
  • calculated SCORE ≥ 5% and <10% for a 10-year risk of fatal CVD
Moderate-risk
  • T1DM (age < 35y) or T2DM (age < 50y)  with diabetes duration <10 years without other risk factors
  • calculated SCORE  ≥ 1 % and  <5% for a 10-year risk of fatal CVD
Low-risk
  • calculated SCORE <1% for a 10-year risk of fatal CVD

SCORE calculator

Management

Lifestyle modification

  • smoking – stop smoking, no exposure to tobacco or cigarette smoke in any form
  • alcohol – reduce alcohol consumption
    • patients who drink >2 alcoholic drinks per day for men or > 1 alcoholic drink a day for women should be counseled to stop or reduce their consumption
    • moderate consumption may be continued (up to 30 g/day for men, up to 20 g/day for women)
  • body weight – target BMI 20-25 kg/m2, target waist circumference <94 cm (men) and <80 cm (women)
  • blood pressure – for most patients, the target is ≤ 130/80 mmHg if tolerated
  • adequate physical activity
    • ideally 30-60 minutes on most days (at 60-75% of the average maximum heart rate)
  • stress reduction
  • adequate sleep
  • healthy diet
    • reduce total fat (saturated and trans) – replace with mono- or polyunsaturated fats
    • reduce total dietary carbohydrates and replace them with unsaturated fats
    • increased intake of wholegrain products, vegetables, fruit, and fish
    • increased dietary fiber intake
    • reduce salt intake to 5-6 g/d (up to 2.4 or 1.5 g/d in secondary prevention)
  • avoid/reduce drugs that promote sodium and water retention (NSAF, sympathomimetics, corticosteroids in susceptible women, or oral contraceptives)
  • maintain normoglycemia – HbA1c <7% (<53 mmol/mol)  → diabetes target values
  • treat dyslipidemia

Target values for hypertension treatment

ESC guidelines 2018
  • the first objective is to lower BP to <140/90 mmHg
    • high normal BP (130–139/85–89 mmHg) – drug treatment may be considered if CV risk is very high due to established CVD, especially in CAD
  • patients <65 years of age:  SBP should be lowered to 120–129 mmHg in most patients if tolerated
    • SPRINT, ACCORD BP, RESPECT, and ESPRIT trials suggest target SBP < 120 mm Hg!
  • patients >65 years: target SPB 130–139 mmHg
  • patients >80 years: target SPB 130–139 mmHg if tolerated
  • target DPB <80 mmHg should be considered for all hypertensive patients, regardless of risk level and comorbidities
WHO guidelines 2022
 

Target values for dyslipidemia treatment

Secondary prevention / very-high risk FH
  • LDL-C reduction ≥ 50% from baseline  +  LDL-C goal < 1.4 mmol/L (< 55mg/dL)
For patients with ASCVD who experience a second vascular event within 2 years (not necessarily of the same type as the first event) while taking maximally tolerated statin therapy
  • consider LDL-C  < 1.0 mmol/L (< 40mg/dl)
Primary prevention
  • very-high risk without FH –  LDL-C reduction ≥ 50% from baseline  +  LDL-C <1.4 mmol/L (<55mg/dL)
  • high risk – LDL-C reduction of  ≥ 50% from baseline and an LDL-C goal of <1.8 mmol/L (<70 mg/dL)
  • moderate risk – LDL-C goal  <2.6 mmol/L (<100mg/dl)
  • low risk – LDL-C goal <3 mmol/L (<116 mg/dL)
  • TAG <1.7 mmol/L (<150 mg/dL) indicates lower risk, and higher levels indicate a need to look for other risk factors
  • ApoB secondary goals are <65, 80, and 100 mg/dL for very-high-, high-, and moderate-risk people, respectively

Very high-risk FH (familial hypercholesterolemia):  FH + ASCVD or major risk factors
High-risk FH: FH without major risk factors

Values based on ESC guidelines 2019

Target values for diabetes treatment

Target values for metabolic syndrome therapy
Fasting glycemia ( ≥ 8 hours after last meal)
  • an indicator of glycemia during the night and morning
  • predictor of cardiovascular complications

≤ 6 mmol/L
Glycemia 1-2 hours after meal
  • independent risk factor for heart and large vessel disease
≤  7,5 mmol/L
HbA1c (glycated hemoglobin)

  • an indicator of long-term DM compensation – the so-called “long sugar”
  • the more sugar in the blood, the more it binds to hemoglobin, the higher the risk of late complications (vascular, nervous)
  • reflects the average glycemia in the previous 3 months (lifetime of the erythrocyte)
  • previously HbA1c expressed in %, now in mmol HbA1c/mol Hb
    • HbA1c value in mmol/mol corresponds to 10 times the original value in % – e.g., originally HbA1c 5.5% – now 55 mmol/mol
 non-diabetics
< 38 mmol/mol
diabetics (well-controlled)
43-53  mmol/mol
Blood pressure  → arterial hypertension
monotherapy or combination; always use ACEI or sartan to prevent and treat nephropathy; in non-diabetics, it reduces the risk of developing diabetes
  < 130/80 mmHg
Lipids  → dyslipidemia
Body mass index (BMI)
in diabetic patients with BMI > 30.0 kg/m2, sibutramine or lipase inhibitors (orlistat) may be indicated in combination with diet and exercise or other pharmacotherapy
 19-25
Waist circumference (men/women)   < 94 cm / < 80 cm
The finding of borderline or mildly abnormal renal function (see below) should lead to more intensive treatment of diabetes and arterial hypertension to achieve the best possible compensation

  • slightly elevated serum creatinine concentration (men 115-133 and females 107-124 µmol/L)
  • decreased glomerular filtration rate (< 60 mL/min/1.73 m2, ≤ 1.0 mL/s/1.73 m2)
  • microalbuminuria (30-300 mg/24 h) or albumin/creatinine ratio men 2.5-30, females 3.0-30 g/mol creat.)
  • proteinuria > 300mg/24h

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