Teaching case construct. A man of working age without established ASCVD comes to an appointment. He smokes, his blood pressure at the visit is 150/95 mmHg, his waist circumference is increased, and his father had a myocardial infarction before 55. The lipid profile is not ready yet. The question of the lesson: which of these facts already change the risk assessment, even before the LDL-C number?
A risk factor is a characteristic associated with an increased probability of an event. Some factors can be eliminated (smoking), some are corrected by treatment (blood pressure, LDL-C, glycaemia), and some cannot be eliminated but move the person into a different risk category (age, an established diagnosis of ASCVD, familial hypercholesterolaemia).
The observational map of nine factors is the INTERHEART study (Yusuf S. et al., Lancet 2004;364:937–952): 15 152 cases of first myocardial infarction and 14 820 controls in 52 countries. The population attributable fraction of nine factors (ApoB/ApoA1 ratio, smoking, arterial hypertension, diabetes mellitus, abdominal obesity, psychosocial factors, insufficient consumption of vegetables and fruit, insufficient physical activity, alcohol) was about 90% in men and about 94% in women. This is an observational association in a case-control design. It shows that first myocardial infarctions in different regions of the world cluster around the same set of conditions. It does not prove that eliminating each factor will reduce myocardial infarctions in the same proportion: for LDL-C and smoking there are separate lines of evidence, for psychosocial stress weaker ones.
Non-pharmacological factors that ESC/EAS 2019 and the 2021 prevention guidelines include in management.
- Tobacco smoking is an eliminable factor; cessation is mandatory at any level of risk.
- Blood pressure. In the ESC/EAS 2025 risk category table, a "markedly elevated single risk factor" stands separately: BP ≥180/110 mmHg by itself already places a person at high risk, even without a scale.
- Diabetes mellitus. The risk category depends not on the label "diabetes" but on target organ damage, duration and the number of additional factors — this is discussed in the next lesson.
- Chronic kidney disease. eGFR 30–59 mL/min/1.73 m² is high risk; eGFR <30 mL/min/1.73 m² is very high, according to Table 3 of the 2025 focused update.
- Obesity and physical inactivity. In Box 1 of the 2025 focused update they are listed as risk modifiers beyond SCORE2.
- Family history of premature CVD: men <55 years, women <60 years (Box 1, ESC/EAS 2025).
The Kazakhstan Ministry of Health clinical protocol No. 196/2023 sets the threshold for "early" ASCVD slightly differently in its definition of atherogenic dyslipidaemias: men <55 years, women <65 years. For lipid profile screening the same protocol lists as subject to examination men >40 years and women >55 years or with early menopause, as well as all smokers, all with BP ≥140/90 mmHg or on continuous antihypertensive therapy, all with xanthomas (nodular cholesterol deposits in the skin and tendons), xanthelasmas (flat yellow cholesterol plaques on the eyelids), arcus cornealis (a greyish-white ring of lipid at the periphery of the cornea), diabetes, obesity (BMI >25 kg/m² or waist circumference ≥94 cm in men and ≥80 cm in women), CKD with eGFR <60 mL/min, systemic connective tissue diseases, abdominal aortic aneurysm ≥3.0 cm. This is a list of whom to look for, not a list of diagnoses.
Risk modifiers beyond the scale (Box 1, ESC/EAS 2025) are not independent diagnoses of "very high risk" but a reason to reconsider the category in a person at a decision threshold: high-risk ethnicity (for example, South Asian), stress and social deprivation, chronic immune-mediated inflammatory diseases, psychiatric disorders, premature menopause, pre-eclampsia and hypertensive disorders of pregnancy, HIV infection, obstructive sleep apnoea, persistently elevated high-sensitivity CRP (>2 mg/L), elevated Lp(a).
The boundary of the lesson. Age and male sex increase risk — these are input variables of SCORE2, not "a disease that is treated". They cannot be "removed". They are taken into account so as not to underestimate a young smoker with familial hypercholesterolaemia (the scale does not "see" him as very high risk, but the disease does) and not to overestimate an isolated cholesterol number in a person without other factors.
Practical conclusion. Collecting risk factors is not a questionnaire "for the medical record". Each item either changes the risk category, or is a modifier at a decision threshold, or points to secondary dyslipidaemia (hypothyroidism, nephrotic syndrome, cholestasis, alcohol, drugs), which the Kazakhstan Ministry of Health protocol No. 196 requires to be excluded before starting lipid-lowering therapy.