Lipid management

The modern frame for cardiovascular prevention has shifted from "fix the cholesterol number when it goes up in midlife" to "reduce the cumulative lifetime burden of cholesterol-carrying particles in the arterial wall, the earlier the better." Genetic and biomarker evidence both point in the same direction: the dose × time integral of apolipoprotein B (apoB)–containing particle exposure determines plaque progression, and intervening earlier produces vastly more benefit per unit of cholesterol lowered than intervening late. The 2026 ACC / AHA Guideline on the Management of Dyslipidemia codifies the shift — reinstating numeric targets, integrating coronary artery calcium scoring as the primary reclassifier, mandating universal lipoprotein(a) screening, and laying out a stepwise escalation through statin, ezetimibe, bempedoic acid, PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition, and (imminently) RNA-interference therapy for the genetically driven Lp(a) burden that 20% of adults carry. This article walks the full picture.

The shift: cumulative exposure, not snapshot cholesterol

Evidence: Strong — converging Mendelian-randomization, genetic, and long-cohort (CARDIA) data.

The historical model of cholesterol-driven heart disease treated a lipid panel as a current state — high LDL today, treat today. The modern biological view, codified by Ference, Braunwald, and Catapano in a 2024 Nature Reviews Cardiology synthesis, is that atherosclerosis is the integral of apoB-containing lipoprotein exposure over time, not a snapshot measurement.^[1]

Each apoB-containing particle that traverses the arterial wall has a probability of being trapped and retained. Over decades, retained particles oxidise, recruit macrophages, drive plaque formation, and progressively narrow vessels. The total disease burden is determined by how high your particle count has been multiplied by how long it has been that high.

The CARDIA study — 4,958 asymptomatic adults enrolled at age 18–30 and followed for a median 16 years after they turned 40 — quantified this directly. Cardiovascular event risk tracked the area under each person's curve of LDL cholesterol (LDL-C) plotted against age — each additional 100 mg/dL-years of cumulative exposure raised risk by about 5% (hazard ratio 1.053), independent of their LDL-C at any single point in time. Crucially, the timing of that exposure mattered independently — the same area accumulated at a younger age produced a larger risk increase than the same area accumulated later.^[2]

Mendelian-randomization studies — using genetic variants that produce naturally low lifelong LDL as a proxy for lifelong pharmacological lowering — show up to a threefold greater proportional risk reduction per unit of LDL lowered when the lowering begins early, versus the same reduction starting in midlife with statins. Atherosclerosis you never grow is much easier to prevent than atherosclerosis you've already accumulated.^[3] The longevity implication: lipid management isn't a problem to solve at age 55; it's a cumulative exposure to defend against starting much earlier.

The biomarker that matters: apoB, not LDL cholesterol

Evidence: Strong (apoB is at least as good a predictor as LDL-C, and superior under discordance); Moderate for the incremental outcome benefit of acting on apoB rather than LDL-C, which rests on observational cohorts.

For most of medical history, the primary cholesterol metric has been low-density lipoprotein cholesterol (LDL-C) — a measurement of how much cholesterol mass is being carried inside LDL particles. The clean biology turns out to be one level deeper.

Every atherogenic particle in your bloodstream — LDL, intermediate-density lipoprotein (IDL), very-low-density lipoprotein (VLDL), and lipoprotein(a) — carries exactly one molecule of apolipoprotein B (apoB) on its surface. Measuring plasma apoB therefore gives a direct stoichiometric count of how many atherogenic particles you have in circulation. LDL-C, by contrast, measures only the cholesterol mass inside one subset of those particles, and the cholesterol-per-particle ratio varies considerably between individuals.^[4]

When particles are smaller, denser, and depleted of cholesterol — as in metabolic syndrome, insulin resistance, and some genetic patterns — the LDL-C number can look reassuring while the particle count is dangerously high.

The discordance is bigger than the field assumed

A 2024 JAMA Cardiology analysis by Sayed, Sniderman and colleagues quantified the LDL-C / apoB discordance directly in 12,688 adults from the US National Health and Nutrition Examination Survey (NHANES).^[5] At a standard LDL-C of 100 mg/dL, the median apoB was 80 mg/dL. The 95% range, however, spanned 66 to 99 mg/dL of apoB at that same LDL-C. Discordantly high apoB wasn't restricted to people with overt metabolic syndrome — substantial numbers of metabolically healthy, normal-BMI, normal-fasting-glucose adults had it.

A 375,544-person UK Biobank analysis of discordance confirmed the clinical consequences. In adults with discordantly high apoB relative to their LDL-C, the risk of major cardiovascular events ran 11% higher independently of absolute LDL-C levels.^[6] Mediation analysis showed VLDL particles and triglycerides explaining 25–27% of the excess risk, but apoB itself remained the dominant residual predictor even after adjusting for HDL.

The 2026 ACC / AHA Dyslipidemia Guidelines now formally recommend apoB measurement, particularly when triglycerides exceed 200 mg/dL, in diabetes, or when standard LDL-C targets are met but residual clinical risk remains.^[7] For longevity-oriented adults running a baseline workup, a one-time apoB measurement is probably worth more than the LDL-C value on the same panel.

Risk estimation: PREVENT, PCE, and the calcium score

Evidence: Moderate for the risk calculators (well-validated for discrimination, but calibration drifts in treatment-naïve adults); Strong for coronary artery calcium as a reclassifier.

Until 2023, the standard US cardiovascular risk calculator was the Pooled Cohort Equations (PCE) — built on older datasets, race-as-biological-proxy, and no kidney function. The American Heart Association replaced it with the PREVENT calculator (Predicting Risk of Cardiovascular Disease Events), now mandated by the 2025 hypertension and 2026 dyslipidemia guidelines.^[8]

PREVENT incorporates estimated glomerular filtration rate, body mass index, statin use, and optionally HbA1c, urine albumin-to-creatinine ratio, and a Social Deprivation Index. It estimates both 10-year and 30-year risk and removes race as a biological predictor.

One important caveat. Because the cohorts PREVENT was trained on had substantial background statin use, the algorithm tends to underestimate the risk of a treatment-naïve healthy adult considering primary prevention.^[9] A comparative analysis of 193,885 participants found PREVENT aligned closely with observed risk in statin-treated patients but underestimated risk in untreated adults. The older PCE actually does better in the untreated. Using PREVENT alone to decide whether a young healthy adult should start a statin can produce systematic undertreatment — exactly the pattern the cumulative-exposure hypothesis argues against.

Coronary artery calcium: the reclassifier that matters most

For adults with borderline (3% to <5%) or intermediate (5% to <10%) 10-year PREVENT risk, the 2026 guidelines now embed coronary artery calcium (CAC) scoring — a non-contrast computed-tomography measurement — as the primary reclassifier. The principle: probability becomes anatomy. If you have measurable coronary calcium, you have subclinical atherosclerosis; you're no longer in a statistical grey zone.

A CAC of zero is one of the few clinical numbers in cardiovascular medicine that genuinely buys time — the so-called "warranty period" during which the absolute risk of a hard event is very low. For an adult with intermediate calculated risk but no measurable calcium, deferring statins for several years before re-imaging is a defensible strategy. For an adult with even a small detectable calcium burden, the framework changes from prevention to plaque modification.

Statins in primary prevention: what the trials actually showed

Evidence: Strong — multiple large randomised trials with hard cardiovascular endpoints.

The bedrock of pharmacological lipid management remains statins — competitive inhibitors of the rate-limiting enzyme in hepatic cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase, HMG-CoA reductase). The drop in intracellular cholesterol forces hepatocytes to upregulate LDL receptors, which then clear circulating apoB-containing particles. Three primary-prevention trials anchor the modern understanding.

JUPITER — 17,802 apparently healthy adults with normal LDL-C (median 108 mg/dL) but elevated high-sensitivity C-reactive protein (≥2.0 mg/L, a marker of low-grade inflammation) — was stopped early at 1.9 years for an extraordinary 44% reduction in the primary composite of cardiovascular events on rosuvastatin 20 mg.^[10] The number needed to treat was 95 over 2 years. The trial also revealed a small but consistent signal of incident type 2 diabetes (2.8% vs 2.3%) — a metabolic tradeoff that's now well-replicated for high-intensity statins and worth incorporating into the consent conversation.

HOPE-3 — a more generalisable cohort of 12,705 intermediate-risk adults — tested low-dose rosuvastatin 10 mg over 5.6 years and produced a 24% reduction in the primary composite of cardiovascular death, non-fatal heart attack, and stroke (number needed to treat 91).^[11] Notably, the lower dose produced no excess diabetes signal and no cognitive harm in adults over 70.

MEGA — 7,832 Japanese adults with hypercholesterolaemia and no prior coronary disease or stroke, randomised to diet alone versus diet plus low-dose pravastatin (10–20 mg) — produced a 33% reduction in the primary endpoint of coronary heart disease (66 vs 101 events; hazard ratio 0.67, 95% confidence interval 0.49–0.91) over a mean 5.3 years, despite the lower-baseline-risk population and a modest 18% LDL-C reduction. (A confidence interval is the range in which the true effect most plausibly lies; when it sits entirely below 1.0, as here, the benefit is unlikely to be a chance finding.)^[12] The safety profile was clean: no excess of malignancy or other serious adverse events.

A practical observation across these and other primary-prevention trials: the absolute benefit compounds non-linearly with time. About 0.3 major events prevented per 100 treated at one year; 1.3 at three years; 2.5 at five years.^[13] Statins aren't a "see if it works" intervention. The longevity benefit is a function of sustained adherence over decades.

The SAMSON trial: statin "side effects" are 90% nocebo

Evidence: Moderate — one rigorous n-of-1 crossover trial (n=60), converging with the ASCOT-LLA blinded-vs-unblinded pattern and blinded RCT symptom rates.

The dominant reason statins are discontinued is muscle symptoms — myalgia, weakness. Real-world surveillance puts the reported rate above 10%; double-blind trials consistently show identical rates in placebo and statin arms. The ASCOT-LLA trial captured this directly: identical muscle-symptom reporting in the blinded phase, dramatic divergence after unblinding.

The SAMSON trial (Self-Assessment Method for Statin Side-effects Or Nocebo) was designed to settle the question.^[14] Sixty adults with documented severe statin intolerance — people who had abandoned multiple statins because of side effects appearing within two weeks of starting — were enrolled in an n-of-1 crossover design. They received 12 monthly bottles in randomised order: 4 containing atorvastatin 20 mg, 4 containing placebo, and 4 empty. Daily symptom intensity was tracked via smartphone on a 1–100 scale.

The results landed cleanly:

• No-tablet months: mean symptom score 8.0.
• Statin months: mean symptom score 16.3.
• Placebo months: mean symptom score 15.4 — statistically indistinguishable from the statin months (p = 0.388).

The calculated "nocebo ratio" — the proportion of symptom burden during statin months also experienced during placebo months — was 0.90. About 90% of statin "side effects" in this severely intolerant cohort were attributable to the expectation of harm, not pharmacology. When researchers showed each participant their own n-of-1 data at the end, 50% successfully restarted statin therapy within six months.

The implication for practice isn't that statin myopathy is fake — true rhabdomyolysis with elevated creatine kinase is a documented if rare event. But the typical myalgia profile that leads patients to abandon therapy is overwhelmingly psychological in origin, and the careful presentation of personalised data can salvage adherence in most cases.

CoQ10 is widely tried for statin muscle symptoms — statins do lower it — but the randomized evidence is mixed, and against a 90% nocebo background any uncontrolled "response" is hard to attribute to the supplement. It is cheap and safe enough to trial, but not a substitute for the n-of-1 frame above. See CoQ10.

When statins aren't enough: ezetimibe, bempedoic acid, PCSK9 inhibitors

Evidence: Strong — each agent has a dedicated cardiovascular-outcomes trial (IMPROVE-IT, CLEAR Outcomes, FOURIER, ODYSSEY Outcomes).

The 2010s saw the rise of a clean clinical principle: "lower is better, regardless of how you get there." The historical idea that statins' benefit came from non-cholesterol "pleiotropic" effects has been settled — every drug that lowers apoB by a comparable amount produces a comparable cardiovascular benefit.

Ezetimibe (IMPROVE-IT)

Ezetimibe blocks intestinal cholesterol absorption via the Niemann-Pick C1-Like 1 transporter. The IMPROVE-IT trial added ezetimibe to simvastatin in 18,144 patients after acute coronary syndrome and showed that the further LDL-C reduction produced a proportional further reduction in cardiovascular events.^[15] The safety profile was clean — no excess muscle, liver, or cancer signal. IMPROVE-IT formally settled the "lower is better" question for non-statin lowering: yes, the benefit tracks the cholesterol drop regardless of mechanism.

Bempedoic acid (CLEAR Outcomes)

Bempedoic acid is an inhibitor of ATP-citrate lyase, an enzyme upstream of HMG-CoA reductase in the cholesterol synthesis pathway. Crucially, it's a prodrug activated only by the liver enzyme very-long-chain acyl-CoA synthetase 1 (ACSVL1) — and skeletal muscle doesn't express that enzyme. The drug therefore inhibits hepatic cholesterol synthesis without touching muscle. The pharmacology is designed precisely around the muscle-symptom problem.

The CLEAR Outcomes trial randomised 13,970 adults with documented statin intolerance and elevated LDL-C (mean 139 mg/dL) to bempedoic acid or placebo.^[16] Headline results published in NEJM 2023:

• 13% reduction in the primary four-component composite of major adverse cardiovascular events (MACE — cardiovascular death, heart attack, stroke, or coronary revascularisation; hazard ratio 0.87).
• 15% reduction in the three-component version (cardiovascular death, heart attack, stroke; hazard ratio 0.85), and a 23% reduction in heart attacks specifically.
• No new-onset diabetes signal (unlike statins).
• Reduced major adverse limb events in patients with peripheral artery disease.

For an adult with documented true statin intolerance — or with a strong preference to avoid the statin-class diabetes signal — bempedoic acid is now a defensible first-line option.

PCSK9 inhibitors (FOURIER, ODYSSEY Outcomes)

The discovery of the PCSK9 protein reset the upper limit of pharmacological cholesterol lowering. PCSK9 binds hepatic LDL receptors and tags them for destruction, limiting the cell's clearing capacity. Monoclonal antibodies that bind and neutralise circulating PCSK9 prevent this — allowing massive sustained upregulation of LDL receptors and rapid clearance of circulating apoB particles.

FOURIER added evolocumab to maximally-tolerated statins in 27,564 adults with established cardiovascular disease and produced:^[17]

• 59% reduction in LDL-C versus placebo — median fell from a baseline of 92 mg/dL to 30 mg/dL.
• 15% reduction in the primary 5-component MACE composite.
• 20% reduction in the 3-component MACE composite.

The event-curve separation widened over time, exactly as cumulative-exposure theory predicts — early lowering produces small acute benefit; sustained lowering produces compounding benefit over years. ODYSSEY Outcomes replicated the pattern with alirocumab in 18,924 post-acute-coronary-syndrome patients.

The two practical revelations from the PCSK9 trials: humans tolerate LDL-C levels in the 20–30 mg/dL range — physiologically equivalent to neonatal levels — without measurable neurological, cognitive, or endocrine harm; and the rate-limiting step in lowering LDL-C in adults with established disease isn't pharmacological capacity but cost and access.

Lipoprotein(a): the silent monogenic risk

Evidence: Strong for Lp(a) as a causal, genetically-fixed risk factor; Weak / preliminary for treatment benefit — no outcomes trial of an Lp(a)-lowering drug has yet reported.

For roughly 20% of the global population — over a billion adults — cardiovascular risk is dominated by a single particle that no current statin meaningfully addresses: lipoprotein(a), or Lp(a).

Lp(a) is an LDL-like particle with one bonus feature: a covalently attached apolipoprotein(a) tail that's structurally similar to plasminogen. That makes Lp(a) atherogenic (via the apoB core driving plaque), pro-thrombotic (interfering with fibrinolysis), and pro-inflammatory (carrying oxidised phospholipids). The combination produces excess risk for both coronary disease and calcific aortic valve stenosis.^[18]

Lp(a) levels are >90% genetically determined. They're stable across the lifespan. Diet, exercise, and weight loss don't move them. Statins don't lower them — in some patients statins actually raise Lp(a) by ~20%. Ezetimibe is inactive. Only PCSK9 inhibitors (~30% reduction) and lipoprotein apheresis (effective but resource-intensive) currently address it.

The 2026 ACC / AHA guidelines now explicitly recommend that every adult have Lp(a) measured at least once in their lifetime. The test is cheap, the result is stable, and it identifies adults whose cardiovascular risk profile is fundamentally different from what their LDL-C and apoB suggest.

RNA-interference therapies: the imminent shift

A new class of drugs designed specifically to silence Lp(a) production at the hepatic mRNA level is advancing rapidly through phase 3 trials:

The Lp(a) HORIZON trial of pelacarsen (80 mg subcutaneously monthly) — roughly 8,300 patients with established cardiovascular disease and baseline Lp(a) ≥70 mg/dL — is the first cardiovascular-outcomes trial of any Lp(a)-lowering therapy, and the binary proof-of-concept event for the entire class.^[19] Because it is event-driven, the topline readout has slipped from 2025 into 2026 and had not yet reported as of mid-2026. The critical caveat: no trial has yet shown that lowering Lp(a) reduces cardiovascular events. Phase 2 established that pelacarsen drops Lp(a) by ~80%, but whether that translates into fewer heart attacks and strokes is exactly the question HORIZON is powered to answer — a positive result would validate Lp(a) as a treatable risk factor for the first time; a null would be a major cautionary datapoint. For the 20% of adults carrying clinically elevated Lp(a), this is the largest pending question in preventive cardiology.

What the 2026 dyslipidemia guidelines actually say

Evidence: Strong — current US multisociety guideline consensus, built on the trials above.

The 2026 ACC / AHA / Multisociety guideline replaced the older 2018 cholesterol guideline with a more aggressive framework, foregrounding apoB and universal Lp(a) screening.^[20] The headline changes:

1. Numeric LDL-C targets are back. After years of "high-intensity statin" rather than specific numbers, the guideline reinstated explicit goals:
   • <100 mg/dL for borderline (3% to <5% 10-year PREVENT) and intermediate risk (5% to <10%)
   • <70 mg/dL for high-risk primary prevention
   • <55 mg/dL for secondary prevention (established cardiovascular disease)
2. PREVENT replaces the Pooled Cohort Equations — with the caveat that PREVENT tends to underestimate risk in treatment-naïve adults.
3. Coronary artery calcium scoring is the primary reclassifier in the borderline and intermediate-risk zones.
4. ApoB measurement is recommended when triglycerides exceed 200 mg/dL, in diabetes, or when LDL-C targets are met but residual clinical suspicion remains.
5. Universal Lp(a) screening at least once in a lifetime.
6. Earlier screening for familial hypercholesterolemia — starting around age 9 in children with strong family history; pharmacotherapy considered in young adults with LDL-C ≥160 mg/dL plus family history.
7. Sequential escalation pathway: lifestyle → high-intensity statin → add ezetimibe or bempedoic acid → add PCSK9 inhibitor.

Practical guidance

1. Get one baseline apoB measurement, and one lifetime Lp(a) measurement. Both are inexpensive, both add genuine information that an ordinary lipid panel doesn't capture. Most adults have never had either drawn. Both belong on the broader midlife lab panel, alongside the metabolic and inflammatory markers that interact with apoB-driven risk.
2. Use PREVENT as a starting point, but be aware it underestimates risk in treatment-naïve adults. Don't let a 6% 10-year PREVENT score talk you out of aggressive prevention if your family history, lifelong LDL trajectory, or other risk-enhancing factors suggest higher real risk.
3. For borderline or intermediate calculated risk, consider a coronary artery calcium scan. A zero CAC buys real time. Any detectable CAC moves you from probability to anatomy, and the target tightens to <100 mg/dL.
4. Start lipid optimisation early — by your 30s and 40s, not your 60s. The cumulative-exposure math is the most under-appreciated piece of the field. Late intervention is highly worthwhile but late intervention loses to early intervention on absolute lifetime risk.
5. Eat the Mediterranean pattern by default. See Dietary patterns. It's the single largest non-pharmacological lever — PREDIMED's roughly 30% reduction in major events is unmatched in the dietary-pattern literature. Olive oil, legumes, nuts, fish, vegetables; not red and processed meat (Foods to limit).
6. If you're on a statin and have muscle symptoms, work with your clinician on the n-of-1 frame from SAMSON before abandoning therapy. Roughly 90% of the symptoms in severely intolerant patients turn out to be nocebo. Switching statins, dose-reducing, alternate-day dosing, or running a placebo-controlled trial of one with your own doctor often salvages adherence.
7. If you genuinely can't tolerate statins, bempedoic acid is now an evidence-supported alternative — a 13% reduction in major cardiovascular events in CLEAR Outcomes, glucose-neutral, designed around the muscle problem.
8. If LDL-C remains elevated on maximally-tolerated statin (or statin plus ezetimibe), ask about a PCSK9 inhibitor. Driving LDL into the 30 mg/dL range is safe and slows plaque progression.
9. If your Lp(a) is high, you have time, but watch the pipeline. Pelacarsen's Phase 3 cardiovascular-outcomes results — the first ever for an Lp(a)-lowering drug — are expected in 2026; olpasiran later in 2026; lepodisiran and muvalaplin behind. These trials will establish whether lowering Lp(a) reduces events at all, so treat the payoff as promising but unproven until HORIZON reads out. If it succeeds, the first targeted Lp(a)-lowering therapy would rewrite the risk calculus for one-fifth of adults.
10. Don't smoke; manage blood pressure and weight; maintain aerobic fitness. The lipid story sits inside the wider cardiovascular-risk frame. See Blood pressure management, VO₂ max, and Smoking and nicotine.

What's overrated

• "My LDL is normal so I'm fine." With LDL-C / apoB discordance in roughly a quarter of adults, a normal LDL-C doesn't rule out high atherogenic particle burden. Get the apoB.
• The "pleiotropic effects" theory of statins. Settled by IMPROVE-IT and CLEAR Outcomes — the cardiovascular benefit tracks the cholesterol drop, not the drug class.
• Bedtime-of-life dietary cholesterol fears (eggs, etc.). The dietary-cholesterol-to-serum-cholesterol pathway is weak in most adults. Saturated fat composition and overall dietary pattern dominate; see Foods to limit.
• HDL cholesterol as a target. Higher HDL is no longer treated as a therapeutic goal — drugs that raise HDL didn't improve outcomes in randomised trials. HDL is a marker, not a lever.
• Annual cholesterol panels as the diagnostic basis. A point-in-time LDL-C number is much less informative than the trajectory, the apoB, the Lp(a), and the calcium score together.
• Discontinuing statins because of perceived side effects without an n-of-1 trial. SAMSON nailed it: in severely intolerant adults, 90% of the symptom burden is nocebo, and half can restart therapy when shown their own data.

Further reading

• Ference BA, Braunwald E, Catapano AL. The LDL cumulative exposure hypothesis — evidence and practical applications. Nature Reviews Cardiology 2024.^[21]
• 2026 ACC/AHA/Multisociety guideline on the management of dyslipidemia. J Am Coll Cardiol 2026;87:2624.^[22]
• Sayed A et al. Individual Variation in the Distribution of Apolipoprotein B Levels Across the Spectrum of LDL-C or Non-HDL-C Levels. JAMA Cardiol 2024.^[23]
• Du Y et al. Impact of LDL-C and Apolipoprotein B Level Discordance and associated Lipoprotein Particle Alterations on Cardiovascular Outcomes in a large primary prevention population. Eur J Prev Cardiol 2025.^[24]
• Ridker PM et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein — JUPITER. NEJM 2008.^[25]
• Yusuf S et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease — HOPE-3. NEJM 2016.^[26]
• Nakamura H et al. Primary prevention of cardiovascular disease with pravastatin in Japan — MEGA Study. Lancet 2006.^[27]
• Domanski MJ et al. Time Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk — CARDIA. J Am Coll Cardiol 2020.^[28]
• Howard JP et al. Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment (SAMSON). J Am Coll Cardiol 2021.^[29]
• Cannon CP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (IMPROVE-IT). N Engl J Med 2015.^[30]
• Nissen SE et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients — CLEAR Outcomes. NEJM 2023.^[31]
• Sabatine MS et al. Evolocumab and clinical outcomes in patients with cardiovascular disease — FOURIER. NEJM 2017.^[32]
• Kronenberg F et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J 2022.^[33]
• Lp(a) HORIZON trial — pelacarsen Phase 3 cardiovascular outcomes (Novartis / Ionis).^[34]

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