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#dyslipidemia #ldl-c #primary-prevention #ASCVD #guidelines #lipoprotein-a #triglycerides

Dyslipidemia

Contents. #Definition · #Atherogenic targets — LDL-C, non-HDL-C and ApoB · #Screening and diagnosis · #Treatment goals by risk category · #Lifestyle · #Agents at a glance · #Hypertriglyceridaemia · #Lipoprotein(a) · #Emerging therapies · #Contradictions / Open Questions

Detailed pages. concepts/Dyslipidemia-Management — the drugs and the order to use them in: statin intensity, ezetimibe, PCSK9 agents, bempedoic acid, inclisiran, statin intolerance, secondary prevention and special populations.

Definition

Dyslipidaemias are disorders of blood lipid levels: elevated LDL-C and total cholesterol, hypertriglyceridaemia, and elevated lipoprotein(a). Management targets atherogenic lipoprotein reduction to lower ASCVD risk and, separately, prevention of acute pancreatitis in severe hypertriglyceridaemia.

The 2026 ACC/AHA guideline is the current comprehensive framework and moves the target beyond LDL-C alone to non-HDL-C and ApoB, adopting PREVENT for risk estimation, reinstating absolute LDL-C and non-HDL-C goals, recommending universal Lp(a) measurement for adults, and codifying ApoB as a marker to guide intensification (sources/lipid-aha-2026, rating: very high). ESC 2025 keeps its 2019 targets unchanged and concentrates on which agents to use, when to start them, and in whom (sources/lipid-esc-2025, rating: very high).

Key Concepts

Atherogenic targets — LDL-C, non-HDL-C and ApoB

Screening and diagnosis

Treatment goals by risk category

Sorted by LDL-C goal, strictest first; rows sharing a goal are ordered by indication.

Risk category LDL-C goal Non-HDL-C goal Guideline
Severe hypercholesterolaemia, LDL-C ≥190 mg/dL (4.9 mmol/L) <55 mg/dL (1.4 mmol/L) with ASCVD; <70 mg/dL (1.8 mmol/L) if FH or additional risk; <100 mg/dL (2.6 mmol/L) otherwise — AHA COR 1
Very strict control
ASCVD, very high risk <55 mg/dL (1.4 mmol/L) and ≥50% reduction <85 mg/dL (2.2 mmol/L) ESC I A; AHA COR 2a
CAC ≥1000 AU <55 mg/dL (1.4 mmol/L) <85 mg/dL (2.2 mmol/L) AHA COR 1
Strict control
ASCVD, not very high risk <70 mg/dL (1.8 mmol/L) <100 mg/dL (2.6 mmol/L) ESC I A; AHA COR 2a
CAC 300–999 AU <70 mg/dL (1.8 mmol/L); consider intensifying to <55 mg/dL (1.4 mmol/L) — AHA COR 1 / 2a
CAC 100–299 AU or ≥75th centile <70 mg/dL (1.8 mmol/L) — AHA COR 1
Diabetes with multiple risk factors <70 mg/dL (1.8 mmol/L) and ≥50% reduction <100 mg/dL (2.6 mmol/L) AHA COR 2a
Primary prevention, high (≥10%) <70 mg/dL (1.8 mmol/L) <100 mg/dL (2.6 mmol/L) AHA
Normal control
CAC 1–99 AU or <75th centile <100 mg/dL (2.6 mmol/L) — AHA COR 2a
Diabetes 40–75 y, no ASCVD <100 mg/dL (2.6 mmol/L) and 30–49% reduction <130 mg/dL (3.4 mmol/L) AHA COR 1
Primary prevention, intermediate (5–<10%) <100 mg/dL (2.6 mmol/L) <130 mg/dL (3.4 mmol/L) AHA
Primary prevention, borderline (3–<5%) <100 mg/dL (2.6 mmol/L) <130 mg/dL (3.4 mmol/L) AHA
Primary prevention, moderate risk by SCORE2 <100 mg/dL (2.6 mmol/L) — ESC IIa A

ESC states its targets in mmol/L and ACC/AHA in mg/dL; both are shown throughout. Cholesterol converts at 38.67 mg/dL per mmol/L, which also holds for non-HDL-C.

Sources for the table: ACC/AHA primary prevention, secondary prevention, CAC and diabetes goals (sources/lipid-aha-2026, rating: very high); ESC targets (sources/lipid-esc-2025). CAC of 0 with no higher-risk conditions supports deferring therapy and reassessing in 3–7 years (COR 2a), and incidental CAC on a non-cardiac CT should inform the decision (COR 1) (sources/lipid-aha-2026).

Very high risk ASCVD means ≥2 major ASCVD events, or 1 major event plus ≥2 high-risk conditions — recurrent ACS within 12 months, prior MI, ischaemic stroke, symptomatic PAD, age ≥65, FH, prior CABG/PCI, diabetes, hypertension, CKD (eGFR 15–59), current smoking, LDL ≥100 on maximum statin plus ezetimibe, or heart failure (sources/CCS-AHA-2023, rating: very high).

The <55 versus <70 question has one direct RCT. Ez-PAVE randomized 3,048 South Korean patients with established ASCVD to intensive (target <55) or conventional (target <70) therapy for a median of 3.0 years, open-label. Achieved LDL-C was 56 versus 66 mg/dL. The primary composite (cardiovascular death, nonfatal MI, nonfatal stroke, any revascularisation, unstable angina hospitalisation) occurred in 6.6% versus 9.7%, HR 0.67 (95% CI 0.52–0.86; P=0.002). The benefit was carried by revascularisation (HR 0.63) and nonfatal MI (HR 0.46); cardiovascular death (31 vs 29 all-cause deaths), nonfatal stroke and unstable angina hospitalisation were individually null. Only 60.8% of the intensive arm reached target (sources/intensive-ldl-ezpave-nejm-2026, rating: high).

Lifestyle

Agents at a glance

Class LDL-C reduction Route Detail
High-intensity statin ≥50% Oral concepts/Dyslipidemia-Management
Moderate-intensity statin 30–49% Oral concepts/Dyslipidemia-Management
Ezetimibe 18% alone; +25% with statin Oral daily concepts/Dyslipidemia-Management
PCSK9 mAb 45–64% SC 2–4 weekly concepts/PCSK9-Inhibitors
Inclisiran 48–52% SC 6-monthly entities/Inclisiran
Bempedoic acid 21–24% alone; +17–18% with statin Oral daily concepts/Dyslipidemia-Management
Bile acid sequestrants 10–27% Oral concepts/Dyslipidemia-Management
Obicetrapib (investigational) ~30% add-on Oral daily concepts/CETP-Inhibitors
Olezarsen (FCS only) −43.5% triglycerides SC monthly concepts/APOC3-Inhibition
Icosapent ethyl −15 to −61% triglycerides Oral concepts/Hypertriglyceridemia-Management

Reduction figures are the ACC/AHA class summary (sources/lipid-aha-2026, rating: very high). The order in which these are added, the evidence behind each step, and the management of statin intolerance are on concepts/Dyslipidemia-Management — in summary: high-intensity statin first, ezetimibe second, PCSK9 mAb only after maximum statin plus ezetimibe, with bempedoic acid and inclisiran reserved for when those fail or cannot be used.

Hypertriglyceridaemia

Lipoprotein(a)

Emerging therapies

Contradictions / Open Questions

Connections

Sources