A person after myocardial infarction on a high-intensity statin, LDL-C 1.3 mmol/L, is formally "at target" for very high risk. Yet the risk is not zero. Residual risk is the probability of an event that persists after the LDL-C target has been reached. Three frequent carriers of this remainder: triglycerides and low HDL-C, lipoprotein(a), and diabetes mellitus and CKD as "amplifiers" of atherosclerosis.
Lipoprotein(a), Lp(a) is an LDL-like particle with an additional covalently bound apolipoprotein(a). Its concentration is more than 90% genetically determined and relatively stable throughout life (ESC/EAS 2025). The 2025 focused update: Lp(a) levels above 50 mg/dL (105 nmol/L) should be considered in all adults as a factor that enhances cardiovascular risk, with higher values associated with a greater increase in risk (IIa B). Risk begins to rise slightly from about 30 mg/dL (62 nmol/L) and becomes clinically significant above 50 mg/dL — according to data the document cites from populations in the United Kingdom, Denmark and the USA; the strongest associations are with myocardial infarction and aortic valve stenosis, weaker ones with peripheral artery disease and heart failure, and the weakest with ischaemic stroke and all-cause mortality. This is an epidemiological and genetic association of a continuous type, not proof that pharmacological lowering of Lp(a) reduces events: specific Lp(a)-lowering drugs are still in trials in 2025, and the focused update states directly that lowering Lp(a) has not yet been shown to reduce ASCVD.
Kazakhstan Ministry of Health protocol No. 196: Lp(a) is measured at least once in a lifetime; ≥50 mg/dL is associated with increased ASCVD risk; ≥180 mg/dL (≥430 nmol/L) is an inherited extremely high risk comparable to heterozygous FH. The discrepancy between the thresholds "optimal <50 or <30 mg/dL" in Table 13 of the protocol and the European "risk modifier >50" should be read as different tasks: Table 13 gives desirable values, ESC gives the threshold from which the risk category may be upgraded.
Triglycerides. Kazakhstan Ministry of Health protocol: statins are the drug of first choice for TG >2.3 mmol/L in high-risk patients (I, B). Fenofibrate is IIa B for secondary prevention in those who have reached the LDL-C target but have TG >2.3 mmol/L. n-3 PUFA 2 g twice daily as the next step. ESC/EAS 2025 specifies the molecule: high-dose icosapent ethyl (2 g twice daily, as in REDUCE-IT) should be considered (IIa B) in high/very-high-risk patients with fasting TG of 1.52–5.63 mmol/L (135–499 mg/dL) on a statin. REDUCE-IT showed a reduction in events; STRENGTH with an EPA+DHA mixture did not. The course does not treat "omega-3" as an equivalent class.
Inflammation. Persistently elevated hs-CRP >2 mg/L is a risk modifier in Box 1 of ESC/EAS 2025. Within this course it is not an indication to prescribe "an anti-inflammatory for atherosclerosis": the anti-inflammatory strategy in ESC CCS 2024 is placed in a separate subsection on event prevention and is not discussed here as a standard of the initial visit.
Diabetes mellitus and CKD are not "comorbidities" but reclassification. Diabetes with target organ damage or long duration is very high risk regardless of the scale. Severe CKD is too. In these patients the LDL-C target is that of very high risk, even if there has not yet been a myocardial infarction.
A special item of the 2025 focused update that did not exist in 2019 as a class I recommendation: in people with HIV in primary prevention aged ≥40 years, statins are recommended regardless of estimated risk and LDL-C level (I B) — on the basis of REPRIEVE (7769 participants aged 40–75 on ART, pitavastatin 4 mg, stopped early, 35% reduction in MACE, HR 0.65; 95% CI 0.48–0.90; NNT 106 over 5 years). The choice of statin takes into account interactions with antiretroviral drugs.
The boundary of the lesson. Residual risk is not a reason to keep adding drugs endlessly "just in case". Each subsequent class must have evidence of event reduction in a comparable population. For Lp(a) there is no such evidence of event reduction by a drug in 2025 — there is a basis for regarding it as a modifier and lowering LDL-C more strongly. For fibrates as a class, a reduction in ASCVD on top of statins has not been established (ESC/EAS 2025 confirms the 2019 class IIb for fenofibrate/bezafibrate and states directly that fibrates are not indicated for lowering cholesterol or LDL-C).