Today, I review, link to, and excerpt from The Curbsiders‘ “518: Cardiology Meets Longevity”.*

*Wurtz PJ, Katz G, Williams PN, Watto MF.  “Cardiology Meets Longevity.” The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast March 23, 2026.

All that follows is from the above resource.

Transcript available via YouTube

Metabolic Health, Advanced Lipidology, and Preventing ASCVD

Level up your primary prevention game. Learn when ApoB, Lp(a), and CAC actually change management, how to spot cardiometabolic risk before diabetes declares itself, and how to make smarter lipid decisions beyond the standard panel. We’re joined by Dr. Greg Katz, cardiologist and prevention expert at NYU Langone Health.

Show Segments

• Intro
• Primary Prevention & Metabolic Syndrome (Case 1)
• Beyond the Standard Lipid Panel
• When to Order ApoB
• How Lp(a) Changes Management (Case 2)
• Using CAC/CCTA in the Gray Zone
• Recognizing Early Cardiometabolic Risk
• CGMs, Wearables, and Signal vs Noise (Case 3)
• How to Talk to Patients About Risk
• Take-Home Points

Dr. Katz reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

Cardiology Meets Longevity Pearls

1. ApoB is most useful when the standard lipid panel may be lying to you. In patients with high triglycerides, insulin resistance, central adiposity, or metabolic syndrome, LDL-C can underestimate atherogenic particle burden; when LDL-C and ApoB are discordant, risk generally tracks more closely with ApoB.
2. Lp(a) is not a niche test anymore. A one-time Lp(a) level is worth ordering in all adults, especially those with premature ASCVD, strong family history, unexpectedly severe disease, or risk that seems out of proportion to traditional markers.
3. An elevated Lp(a) usually changes management indirectly, not directly. You usually are not treating the Lp(a) itself yet; you are using it to justify more aggressive treatment of the modifiable parts of risk such as LDL-C, blood pressure, weight, and lifestyle, among others.
4. Coronary artery calcium (CAC) is a decision tool. CAC is most helpful when you are on the fence about starting or intensifying lipid-lowering therapy in primary prevention.
5. Do not order CAC unless you know how the result will change management. The test is most valuable in common gray-zone patients, not when the answer is already obvious from the clinical picture.
6. Coronary CTA and CAC are not interchangeable. CAC is generally the better tool for asymptomatic risk refinement in primary prevention, whereas coronary CTA is more useful when you are evaluating symptoms or need more detailed anatomic plaque information.
7. A normal A1c does not rule out important cardiometabolic risk. Rising triglycerides, low HDL, abdominal adiposity, MASLD, hypertension, sleep apnea, and creeping glucose can all signal insulin resistance* and elevated future risk before diabetes is formally present. [*Google Search Result]
8. The triglyceride-HDL pattern can be a practical clue to metabolic dysfunction. It should not be overinterpreted as a stand-alone diagnosis, but it can help identify patients whose risk is being underestimated by a routine lab review. Clinical validation for these markers is not uniform across all racial and ethnic groups. Clinicians should remain cognizant of these limitations, as the predictive accuracy of specific tools can fluctuate significantly depending on a patient’s background.
9. Statins are still the anchor of primary prevention, even in the era of advanced biomarkers and GLP-1 therapy. Adjunctive medications (ezetimibe, PCSK9 inhibitors) can be added as necessary for statin intolerance, or if further risk lowering is warranted / desired.
10. Risk calculators are starting points, not final answers. Younger patients with strong family history, elevated Lp(a), metabolic dysfunction, or other risk-enhancing features may be higher risk than a pooled calculator suggests, so prevention decisions still require judgment.

Cardiology Meets Longevity 

Primary Prevention for Cardiovascular Disease

Dr. Katz discusses that the trajectory toward a major cardiovascular event often begins decades before the first symptom of angina or the sudden onset of a myocardial infarction. Many patients present with overt signs of metabolic dysfunction, such as abdominal obesity, borderline hypertension, or impaired fasting glucose, that serve as precursors to atherosclerotic cardiovascular disease (ASCVD). The primary goal of prevention is to intervene during this prolonged subclinical phase to alter the patient’s lifetime risk trajectory. Metabolic syndrome, abdominal obesity, hypertension, insulin resistance, dyslipidemia, MASLD, obstructive sleep apnea, and chronic kidney disease often travel together and compound risk over time. The clinical task is not only to estimate risk, but to identify which risk drivers are modifiable and which tools a given patient is actually willing to use. A central tenet of the modern preventive approach is focusing on modifiable risk factors (expert opinion). While a patient cannot control their genetic heritage or the health of their parents, they can exert significant control over the “compound effect” of multiple risk factors over time. Dr. Katz mentions that a reasonable approach to these modifiable risk factors is trying to figure out exactly how “medicalized” a patient wants to be. There are lots of “tools in the toolbelt,” so to speak, but some patients may prefer lifestyle modification first, some may prefer medications up front, and some may prefer some combination of both. Shared decision making and learning about the patient’s goals is an essential first step when partnering together towards a common goal. Remember the human side of medicine, because that’s what matters here. Patients may not have many traditional “medical conditions” at this stage, so the primary focus of the visit can be about understanding dietary patterns, exercise barriers, understanding their sleep and stress patterns, etc. (expert opinion).

Metabolic Syndrome and Cardiometabolic Risk

What is Metabolic Syndrome?

Metabolic syndrome refers to a cluster of cardiometabolic abnormalities that tend to occur together and raise risk for cardiovascular disease, diabetes, and other downstream complications. Common components include elevated waist circumference, high triglycerides, low high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and elevated glucose (Swarup 2024).

Metabolic dysfunction is better understood as a spectrum than a strict binary state. Patients may show early warning signs such as rising triglycerides, lower HDL, rising fasting insulin/glucose, metabolic associated fatty liver disease, or increasing waist size years before formal diabetes develops (Mechanick 2020, expert opinion).

The traditional diagnosis of metabolic syndrome requires the presence of 3 or more metabolic abnormalities (Swarup 2024):

• A waist circumference of more than 40 inches in men and 35 inches in women
• Serum triglycerides level of 150 mg/dL or greater
• Reduced HDL cholesterol, less than 40 mg/dL in men or less than 50 mg/dL in women
• Elevated fasting glucose of l00 mg/dL or greater
• Blood pressure values of systolic 130 mm Hg or higher or diastolic 85 mm Hg or higher

However, it is more helpful to think about any of these factors as red flags towards an increased cardiometabolic risk rather than a binary state of either having metabolic syndrome or not (expert opinion).

Lifestyle Matters

Advanced biomarkers never replace the foundation of lifestyle. Nutritional quality, physical activity, weight management, restorative sleep, and blood pressure control—including the treatment of sleep apnea—remain the bedrock of cardiovascular prevention. Guidelines explicitly emphasize a healthy lifestyle across the lifespan, reinforcing exercise and consistent activity as core therapy (Arnett 2019).

Lifestyle modification can dramatically improve modifiable risk, but it does not erase inherited risk. Patients with a striking family history or markedly elevated Lp(a) may still warrant aggressive preventive measures even when they appear clinically “healthy” (Reyes-Soffer 2022).

Lipids, Atherogenesis, and Metabolic Health

Atherosclerosis starts when cholesterol-carrying particles get into the walls of blood vessels, trigger inflammation, and gradually build plaque. The key idea is that cholesterol cannot move through the bloodstream on its own, so it has to be carried by lipoprotein particles (Nurmohamed 2021).

That is where ApoB comes in. ApoB is the main protein attached to every major atherogenic particle,  including LDL, VLDL, IDL, and Lp(a), so it gives you a direct sense of how many plaque-forming particles are actually circulating (Ference 2018, Sniderman 2019).

Dr. Katz gives us a helpful framework. If you think about traffic: LDL-C tells you how many passengers are traveling, while ApoB tells you how many cars are on the road. And if traffic is what causes the damage, the number of cars is often a much better way to estimate risk.

Interpreting the Traditional Lipid Panel

When reviewing a standard lipid panel, the triglyceride-to-HDL pattern can be a practical initial clue to insulin resistance and metabolic dysfunction (Flores-Guerrero 2023); it is best viewed as a surrogate marker rather than a stand-alone diagnostic test (expert opinion). Keep in mind that its clinical utility is often nuanced by the patient’s ethnicity and sex (Miller 2011, Azarpazhooh 2021). It tracks reasonably well with insulin resistance in White populations (Bibra 2017), but performs less reliably in Black patients and appears more variable in South Asian populations (Salazar 2012,), especially among South Asian women (Mosatafa 2012).

If triglycerides are elevated on a lipid panel, first confirm whether the sample was fasting, since triglycerides are more affected by fasting status than the other standard lipid parameters. The 2018 cholesterol guideline supports either fasting or nonfasting lipids for routine assessment, but fasting testing remains helpful when triglycerides are elevated or interpretation is uncertain. Determining whether a patient was fasting prior to a blood draw is a practical pearl for interpreting lipid results, as postprandial changes can significantly influence specific parameters on the standard panel. You can make an adjustment though; for instance, if a patient presents with a non-fasting sample, you can subtract approximately 10 mg/dL from the reported LDL-C value and 25 mg/dL from the triglyceride level (Mora 2016).

Non-HDL-C is often a superior marker to LDL-C because it captures the cumulative risk from remnant lipoproteins, which are particularly elevated in patients with obesity and metabolic syndrome (Elshazly 2013, Rosenson 2014).

Beyond the Standard Lipid Panel

Why ApoB Can Add Value

Across populations, LDL-C and apoB generally track together, but in individual patients they can become discordant. This matters most in patients with hypertriglyceridemia, insulin resistance, obesity, or metabolic syndrome, where particles may carry less cholesterol per particle. In that setting, LDL-C can look deceptively “okay” even when atherogenic particle number remains high (Soffer 2024, Witt 2025). When apoB and LDL-C disagree, cardiovascular risk tends to align more closely with apoB than with LDL-C. This is one of the strongest practical arguments for measuring apoB in selected patients (Soffer 2024, Linton 2019).

This finding has been replicated across multiple large-scale cohorts, making a compelling case for the use of ApoB in refined risk assessment (Linton 2019, Solnica 2023). Major professional societies, including the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Lipid Association (NLA), now recognize persistently elevated ApoB (especially when triglycerides are above 200 mg/dL) as a “risk-enhancing factor” that can justify more aggressive therapy (Sniderman 2021, Glavinovich 2022, Johannesen 2021, Soffer 2024).

A practical way to think about apoB: it is often most helpful when the standard lipid panel may be underestimating risk. Central adiposity, elevated triglycerides, insulin resistance, and metabolic syndrome are common red flags for discordance (expert opinion). Dr. Katz mentions that you should consider ordering it on everyone at least once, ensuring that it is concordant with LDL-C. If discordant, then it may be the better metric to track.

Implementing ApoB in Clinical Practice

Red flags arise when the ApoB is disproportionately higher than the LDL-C (expert opinion).  As a general rule of thumb, ApoB targets should be approximately 10% to 15% lower than the corresponding LDL-C targets (expert opinion). For example, if a secondary prevention target for LDL-C is < 55 mg/dL, Dr. Katz suggests an appropriate ApoB goal would be roughly 40 to 50 mg/dL.

ApoB can guide the decision to add “nuanced” medications like PCSK9 inhibitors or ezetimibe in patients who have reached LDL goals but still have significant particle (i.e. ApoB) -driven risk.Current evidence supports the broader principle that lower atherogenic lipoprotein burden reduces event risk, but the exact apoB “goal” should be individualized to overall risk, treatment burden, tolerance, and patient preference (expert opinion, Cannon 2015).

New Risk Calculator and Modern Stratification

The AHA PREVENT-ASCVD (PREVENT) calculator was designed to estimate risk for cardiovascular disease, stroke, heart failure, and kidney disease by integrating cardiovascular, kidney, and metabolic health factors. It is a useful starting point for clinician-patient discussion in primary prevention. That said, risk calculators can still underestimate risk in some younger patients, especially those with strong family history, elevated Lp(a), premature risk-factor burden, or other important risk-enhancing features. Thus, calculators are good population tools, but not substitutes for understanding the actual patient in front of you (Anderson 2024, expert opinion).

Key Evolutions in the PREVENT Tool

The PREVENT calculator introduces three fundamental changes to the way cardiovascular risk is quantified. First, it replaces the variable of “race” with “ZIP code” as a proxy for social determinants of health (SDOH).This shift acknowledges that the disparities previously attributed to biological race are more accurately explained by socioeconomic factors, environmental exposures, and healthcare access (Khan 2023).  Second, the PREVENT tool expands the definition of cardiovascular risk to include heart failure as a primary endpoint alongside myocardial infarction and stroke.This “Total CVD” approach reflects the reality that for many patients with metabolic syndrome and hypertension, heart failure is the first and most debilitating manifestation of vascular disease (Khan 2024). Third, the tool provides both a 10-year and a 30-year risk estimate for adults aged 30 to 79. This expanded age range is crucial for identifying young adults who may have low 10-year risk but are on a high-risk lifetime trajectory. The calculator also includes a “risk modifiers” section where clinicians can manually factor in markers such as Lp(a), ApoB, and high-sensitivity C-reactive protein (hsCRP) (Cho 2025, Alebna 2024, Khan 2023, Small 2024).

Addressing the Limitations of Risk Scores

Despite these improvements, all risk calculators remain population-based tools that can fail the individual patient sitting in the exam room. Dr. Katz notes that these tools often miss high-risk young people or may lead to the “over-treatment” of older individuals who have low plaque burden despite their age. For example, if someone with multiple uncontrolled risk factors has a calculated 10-year risk of only 5%, which is below the traditional 7.5% treatment threshold has a heart attack, their life and livelihood are changed forever.

Lp(a): Inherited Risk That the Standard Panel Misses

What Is Lp(a)?

Dr. Katz highlights that Lipoprotein(a), or Lp(a), represents perhaps the most significant under-recognized risk factor in modern preventive cardiology. While approximately 20% of the population—roughly 1 in 5 individuals—possess elevated levels, fewer than 1% of Americans have ever undergone measurement (Razavi 2025, Alebna 2024). Biologically, Lp(a) is an LDL-like particle covalently linked to apolipoprotein(a); it is now well-established as a causal risk factor for both atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (Reyes-Soffer 2022).

Because Lp(a) levels are primarily genetically determined and remain relatively stable across the lifespan, many experts and international organizations now advocate for at least one lifetime measurement in all adults (Razavi 2025, Blumenthal 2026). According to the 2024 NLA focused update*, levels below 75 nmol/L (30 mg/dL) are generally classified as low risk, whereas levels of 125 nmol/L (50 mg/dL) or higher are considered high risk (Koschinsky 2024). Dr. Katz highlights that clinicians must distinguish between mass-based assays (reported in mg/dL) and molar-based assays (reported in nmol/L). Molar-based measurement is preferred as it directly quantifies the number of particles rather than mass (Razavi 2025). It is critical to recognize these distinct units, as laboratory scales vary significantly; for the purposes of this episode, all Lp(a) references heard on air (if unspecified) are referring to the nmol/L measurement.

*A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. J Clin Lipidol. 2024 May-Jun;18(3):e308-e319. doi: 10.1016/j.jacl.2024.03.001. Epub 2024 Apr 1.

Biological Mechanism and Pathogenicity

Lp(a) is an LDL-like particle characterized by the presence of a unique protein, apolipoprotein(a), which is covalently linked to the ApoB-100 molecule. This specialized structure makes Lp(a) a “triple threat” for cardiovascular disease through three distinct mechanisms:

1. Pro-atherogenic: Like LDL, Lp(a) enters the arterial wall and contributes to the formation of atherosclerotic plaques (Boffah 2022, Rosenson 2021).
2. Pro-inflammatory and Pro-oxidative: Lp(a) is the primary carrier of oxidized phospholipids in the blood, which trigger intense vascular inflammation and oxidative stress (Boffah 2022).
3. Pro-thrombotic: Apolipoprotein(a) contains “kringle” repeats that are structurally similar to plasminogen. This homology allows Lp(a) to competitively inhibit plasminogen activation, thereby impairing fibrinolysis and promoting blood clot formation (Attalah 2026).

Due to these properties, Lp(a) particles are estimated to be roughly six times more atherogenic than standard LDL particles (Björnson 2024). Evolutionary biologists hypothesize that elevated Lp(a) may have once provided an advantage by reducing the risk of bleeding after trauma, but in the modern environment of longevity and high-fat diets, it has become a major driver of MI, stroke, and calcific aortic stenosis (Nordestgaard 2016, Tsimikas 2024).

Clinical Utility of Lp(a)

Today, Lp(a) is usually most useful as a risk-enhancer rather than a direct treatment target. Elevated levels can justify more aggressive management of modifiable risk factors such as LDL-C, blood pressure, weight, and lifestyle, especially when paired with a strong family history of premature ASCVD (Koschinsky 2024). In clinical practice, elevated Lp(a) often functions as a tiebreaker in borderline decisions, or as a motivating factor to pursue much more intensive primary prevention. That may mean being quicker to start or intensify statin therapy, add ezetimibe, push harder on lifestyle change, or escalate other prevention strategies, possibly targeting lower ApoB numbers if possible (e.g., 30-40 mg/dL)(expert opinion).

While dedicated Lp(a)-lowering therapies are currently in development, clinical management continues to center on the aggressive treatment of modifiable risk components. Dr. Katz expresses caution regarding emerging small-interfering RNA (siRNA) agents, noting a preference to wait for more definitive outcome data (Tomlinson 2025, O’Donoghue 2024, Malick 2023).

For individuals with markedly elevated Lp(a) levels, Dr. Katz suggests that primary prevention aspirin may be introduced into the shared decision-making conversation. He emphasizes that evaluating the patient’s entire risk profile is vital, as these clinical decisions remain inherently nuanced and are approached on a case-by-case basis.

Lp(a) Testing for Everyone

Lp(a) levels are approximately 80% to 90% genetically determined and remain relatively constant throughout a person’s life. Therefore, universal screening—measuring it once in a lifetime—is recommended by many international guidelines (Blumenthal 2026), though it has not yet been fully adopted in the United States. While thresholds vary, levels around 100 to 150 nmol/L (roughly 50 mg/dL) are generally considered concerning, especially in the context of a strong family history of premature ASCVD.

Coronary Imaging

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