PANCE Blueprint Cardiology (11%)

Patient will present as → a 55-year-old male with a history of obesity and tobacco use who presents for a routine check-up. Labs reveal a total cholesterol of 430 mg/dL and LDL-C of 210 mg/dL. Physical exam reveals yellow deposits around the eyelids (xanthelasma) and firm nodules on the Achilles tendons (tendon xanthomas). He has a faint white ring around his cornea (arcus senilis).

Risk Assessment: The PREVENT™ Calculator (2026 Update)

The 2026 guidelines replace the old Pooled Cohort Equations (PCE) with the AHA PREVENT™ equations for 10- and 30-year ASCVD risk assessment in adults aged 30–79 years.

Key features of PREVENT™:

• Includes eGFR (estimated glomerular filtration rate) as a risk variable
• Removes race-based variables
• Generally yields slightly lower risk estimates than the old PCE

10-Year Risk Categories:

• High Risk: ≥ 10% → statin therapy is recommended
• Intermediate Risk: 5% to < 10% → statin therapy is recommended
• Borderline Risk: 3% to < 5% → statin therapy may be considered after risk discussion
• Low Risk: < 3% → lifestyle therapy is recommended; statin is generally not indicated unless LDL-C ≥ 160 mg/dL or 30-year risk is elevated

Primary Prevention by PREVENT™ Risk Tier — What To Do

Risk Tier	10-Year PREVENT™	Action	Statin Intensity	LDL-C Goal
Low	< 3%	Lifestyle counseling; statin generally not indicated unless LDL-C ≥ 160 mg/dL or 30-year risk ≥ 10%	Moderate (if treating)	< 100 mg/dL
Borderline	3% to < 5%	Lifestyle counseling + risk-benefit discussion; evaluate risk enhancers; consider CAC if uncertain	Moderate (if treating)	< 100 mg/dL; non-HDL-C < 130 mg/dL
Intermediate	5% to < 10%	Start statin therapy; consider CAC if uncertainty remains about intensity	Moderate-to-High	< 100 mg/dL; non-HDL-C < 130 mg/dL
High	≥ 10%	Start high-intensity statin; add ezetimibe, PCSK9i, or bempedoic acid if goals are not met	High-Intensity	< 70 mg/dL; non-HDL-C < 100 mg/dL

⭐ These groups receive lipid-lowering therapy (LLT) regardless of calculated PREVENT™ risk:

(1) Clinical ASCVD, (2) LDL-C ≥ 190 mg/dL, and (3) age 40–75 with diabetes, CKD stage ≥ 3, or HIV on stable antiretroviral therapy.

Only clinical ASCVD qualifies as secondary prevention — the other groups remain primary prevention despite high risk.

• Clinical ASCVD = prior MI, angina, coronary revascularization, ischemic stroke/TIA, PAD, or aortic atherosclerotic disease

⭐ NEW: LDL-C Treatment Targets (2026) — “The Three Numbers: 55, 70, and 100”

Unlike the 2018 guidelines (which had no specific LDL-C targets), the 2026 guidelines restore numerical LDL-C goals:

• Secondary Prevention — Very High Risk (≥2 events OR 1 event + comorbidities): LDL-C < 55 mg/dL
• Secondary Prevention — Not Very High Risk (1 ASCVD event, minimal comorbidities): LDL-C < 70 mg/dL
• Primary Prevention — FH, LDL-C ≥ 190 mg/dL, or High Risk (≥ 10%): LDL-C < 70 mg/dL
• Primary Prevention — coronary artery calcium (CAC) ≥ 1000 AU: LDL-C < 55 mg/dL (treat as very high risk)
• Primary Prevention — Intermediate Risk (5–10%): LDL-C < 100 mg/dL
• Borderline/Low Risk (< 5%): LDL-C < 100 mg/dL (optimal goal if treating)

⭐ NEW: Coronary Artery Calcium (CAC) Scoring

When risk remains uncertain after applying PREVENT™ and risk enhancers, CAC scoring should be considered to guide the decision to initiate or withhold statin therapy:

• Recommended for men ≥ 40 years and women ≥ 45 years with borderline or intermediate PREVENT™ risk
• CAC = 0: Statin therapy may reasonably be deferred (unless diabetes, smoking, or strong family history)
• CAC 1–99: Statin therapy is reasonable
• CAC ≥ 100 or ≥ 75th percentile for age/sex/race: Statin therapy is indicated
• CAC ≥ 1000 AU: LDL-C target < 55 mg/dL (treat as very high risk)

⭐ NEW (2026): Non-Statin Add-On Therapy — Expanded Roles

When LDL-C goals are not met with maximally tolerated statin therapy, add non-statin agents in a stepwise fashion:

Agent	Mechanism	LDL-C Reduction	Class / Notes
Ezetimibe (Zetia)	Inhibits intestinal cholesterol absorption	~18–25%	First-line add-on to statin
Bempedoic Acid (Nexletol)	Inhibits ATP-citrate lyase (upstream of HMG-CoA reductase); activated only in the liver — no myopathy risk, no TG-lowering effect	~18–25%	NEW — expanded role in 2026; useful in selected high-risk patients who need further LDL lowering and in statin-intolerant patients
PCSK9 Inhibitors Evolocumab (Repatha) Alirocumab (Praluent) SQ every 2–4 weeks	Monoclonal antibody blocks PCSK9, increasing LDL receptor recycling	50–60%	Major add-on option for high-risk patients not at goal; high cost and prior authorization often required
Inclisiran (Leqvio) SQ every 6 months	siRNA targeting PCSK9 mRNA — reduces hepatic PCSK9 production	~50%	NEW — Class IIa; useful for patients unable to access or tolerate PCSK9 monoclonal antibodies or who prefer less frequent dosing
Bile Acid Sequestrants Cholestyramine (Questran) Colesevelam (Welchol)	Binds bile acids in gut, increasing hepatic LDL receptor upregulation	~15–18%	Side effects: constipation, bloating; avoid with hypertriglyceridemia (can raise TG)

Board Pearls for Hypercholesterolemia

• “The Three Numbers”: Memorize 55 / 70 / 100 — the LDL-C targets for very high-risk secondary prevention, high-risk primary prevention / severe hypercholesterolemia, and intermediate-risk primary prevention, respectively
• “Earlier and Lower for Longer” — the central message of the 2026 guidelines. Consider starting therapy at age 30 in FH or high long-term risk
• Statin Choice: Atorvastatin and Rosuvastatin are the high-intensity “big guns”
• PREVENT™ thresholds: ≥ 5% (intermediate) = statin recommended; ≥ 3% (borderline) = statin consideration after risk discussion
• Lp(a): If a young patient has an MI with “normal” LDL, check Lp(a)
• Myalgias on statin? Check CK. Tea-colored urine? Think rhabdomyolysis
• Pregnancy: Statins are contraindicated — stop before conception
• Bempedoic acid is a useful option when additional LDL lowering is needed, especially in statin-intolerant patients
• Inclisiran is dosed only twice a year
• CAC = 0 in a low/borderline risk patient? It is reasonable to defer statin therapy
• CAC ≥ 1000 AU = treat like very high risk → LDL-C target < 55 mg/dL
• Only clinical ASCVD = secondary prevention. LDL-C ≥ 190 mg/dL, diabetes, CKD, and HIV are still primary prevention groups

Patient will present as → a 17-year-old female brought in by her parents to check her cholesterol due to a family history of hypertriglyceridemia. Her dad and paternal aunt have a history of pancreatitis. Family history is negative for premature arteriosclerotic cardiovascular disease. Her cholesterol panel is as follows: Total cholesterol 188 mg/dL (< 200), triglyceride 851 mg/dL (< 150), HDL 15 mg/dL (> 50), LDL 102 mg/dL (< 130).

For purposes of management, classify FASTING TG levels as follows:

• Normal – < 150 mg/dL
• Mild to moderate hypertriglyceridemia – 150 to 499 mg/dL
• Moderate to severe hypertriglyceridemia – 500 to 999 mg/dL
• Severe hypertriglyceridemia – ≥ 1000 mg/dL

Normal NON-FASTING triglyceride levels are generally considered below 200 mg/dL

Medications Known to Cause Hypertriglyceridemia:

• Beta-blockers
• High-dose thiazide diuretics/chlorthalidone
• Corticosteroids
• Atypical antipsychotics (clozapine, olanzapine)
• Protease inhibitors (HIV medications)
• Oral contraceptives (high estrogen content)
• Retinoids (isotretinoin)
• Immunosuppressants (cyclosporine)
• Tamoxifen

⭐ NEW: APOC3 Inhibitors — Key Board Points

Mechanism: Apolipoprotein C-III (APOC3) inhibits lipoprotein lipase (LPL), slowing TG clearance. APOC3 inhibitors block hepatic APOC3 production → increased LPL-mediated TG clearance.

Familial Chylomicronemia Syndrome (FCS): A rare genetic condition (biallelic loss-of-function in LPL or LPL-regulating genes) presenting with TG > 1000–2000 mg/dL, recurrent pancreatitis, and poor response to standard TG-lowering therapy. Suspect FCS in patients with severe refractory hypertriglyceridemia and family history of pancreatitis.

• Olezarsen (Tryngolza): Antisense oligonucleotide, 80 mg SQ monthly. Used as adjunct therapy in FCS to lower TG and reduce pancreatitis risk
• Plozasiran: siRNA targeting APOC3, given quarterly, with marked TG lowering in FCS
• Volanesorsen: Approved in Europe/UK/Brazil for FCS — NOT approved in the U.S. due to severe thrombocytopenia risk

⭐ Icosapent Ethyl (Vascepa) vs. Other Omega-3 Preparations — Know the Difference

• For patients with high ASCVD risk and TG > 150 mg/dL despite lifestyle modification and statin therapy, icosapent ethyl (EPA-only) is the preferred omega-3 agent
• REDUCE-IT trial: Icosapent ethyl 4 g/day reduced major cardiovascular events by 25% in high-risk statin-treated patients
• Icosapent ethyl contains EPA only (no DHA). DHA-containing preparations (Lovaza) may increase LDL-C and are acceptable for patients without high ASCVD risk
• Exception: In patients with paroxysmal atrial fibrillation, prefer fibrates over omega-3s due to AF risk
• Omega-3s should be avoided in TG > 880 mg/dL (chylomicronemia) where strict fat restriction is required