What Is Cardiometabolic Disease?
Cardiometabolic disease is not a single condition. It is a system of interconnected metabolic and cardiovascular disorders, all sharing a common root cause. Understanding that root cause changes how you measure, prevent, and treat it.
Reviewed by
William Cromwell, MD
Chief Medical Officer, Precision Health Reports
DEFINITION
What Is Cardiometabolic Disease?
Cardiometabolic disease is a term that describes a cluster of interrelated metabolic and cardiovascular conditions that share a common biological origin and tend to develop together, reinforce one another, and collectively increase the risk of serious health events including heart attack, stroke, and type 2 diabetes.
The word itself reflects this duality: cardio for the cardiovascular system (heart and blood vessels) and metabolic for the body's fundamental processes of energy regulation, glucose management, and lipid metabolism. When these two systems become dysfunctional together, the result is far more dangerous than either problem in isolation.
“The cardiometabolic risk factors that cause people to die prematurely cluster together and amplify each other’s effects — which is precisely why they must be measured and managed together, not in isolation.”
The term is used both clinically and in research to acknowledge that cardiovascular disease and metabolic disease—conditions like type 2 diabetes, obesity, and insulin resistance—are not separate problems to be treated in separate silos. They are facets of a single underlying process, and the most effective prevention and treatment strategies address them as such.
Understanding cardiometabolic disease begins with recognizing that the conditions it encompasses are connected not just statistically, but mechanistically: they share the same root cause, progress along the same biological pathway, and respond to many of the same interventions.
SCOPE
The Conditions Cardiometabolic Disease Encompasses
Cardiometabolic disease is an umbrella term. Under it sit the most prevalent chronic conditions in the developed world:
Atherosclerotic Cardiovascular Disease (ASCVD)
Plaque buildup in arterial walls that narrows blood vessels and raises the risk of heart attack, stroke, and peripheral artery disease.
Insulin Resistance / Prediabetes
The earliest and most treatable stage of cardiometabolic dysfunction which is often present years or decades before any of the above conditions are clinically diagnosed.
Type 2 Diabetes
A metabolic disorder characterized by chronic high blood glucose, resulting from the combination of insulin resistance and eventual pancreatic beta cell failure.
TypNon-Alcoholic Fatty Liver Disease (NAFLD)
Accumulation of fat in the liver not caused by alcohol use, closely linked to insulin resistance and metabolic syndrome, and independently associated with cardiovascular risk.
Metabolic Syndrome
A cluster of five clinical features—abdominal obesity, high triglycerides, low HDL, elevated blood pressure, and elevated fasting glucose—that together signal elevated metabolic risk.
Obesity (particularly central/visceral fat)
Excess visceral fat is both a symptom and a driver of insulin resistance, systemic inflammation, and atherogenic dyslipidemia—all core components of cardiometabolic dysfunction.
These conditions are grouped together because they share mechanisms, risk factors, biomarkers, and treatment targets. A person with metabolic syndrome is at dramatically elevated risk for type 2 diabetes and ASCVD. A person with type 2 diabetes has two to four times the cardiovascular event risk of someone without it.1 Treating them separately, as the larger current healthcare system often does, misses the compounding nature of the underlying biology.
BIOLOGY
The Root Cause: Insulin Resistance
If cardiometabolic disease is a fire, insulin resistance is the spark that starts it. It is the central, unifying driver of the entire syndrome. Critically, it begins years or even decades before any of its downstream diseases manifest as diagnosable conditions.
In healthy individuals, insulin, a hormone produced by the pancreas, signals liver cells, muscle cells, and fat cells to absorb glucose from the bloodstream for energy or storage. In people with insulin resistance, these cells progressively stop responding to that signal. The pancreas compensates by producing more and more insulin, temporarily maintaining normal blood glucose levels…but at a cost that ripples through nearly every metabolic system in the body.
As insulin resistance worsens, it sets off a cascade that touches every cardiometabolic risk factor simultaneously:
Atherogenic dyslipidemia: Elevated VLDL particles, higher LDL particle count, smaller and denser LDL particles, and lower HDL. This pattern, detectable years before diabetes, dramatically increases cardiovascular risk even when LDL cholesterol (LDL-C) appears normal.2
Elevated blood pressure: Insulin resistance impairs nitric oxide synthesis in blood vessels and promotes sodium retention by the kidneys, both of which raise blood pressure.
Chronic low-grade inflammation: Visceral fat tissue secretes inflammatory cytokines, and insulin resistance itself is associated with elevated inflammatory markers like GlycA and hs-CRP, which directly contribute to arterial plaque formation and instability.
Elevated blood glucose: Over time, compensatory hyperinsulinemia fails and blood glucose rises to prediabetic and eventually diabetic levels. Chronic high glucose causes endothelial damage, advanced glycation end products, and accelerated atherosclerosis.
Abdominal (visceral) obesity: Insulin resistance drives preferential fat storage in the visceral depot around the organs which is itself more metabolically active and more damaging than subcutaneous fat.
The critical clinical insight here is that insulin resistance is detectable long before any traditional test values become abnormal. Fasting glucose and HbA1c can remain in the "normal" range for years or decades while insulin resistance is actively worsening and driving atherosclerosis. This is why advanced biomarker testing, particularly the LP-IR score, is essential for early identification of cardiometabolic risk.
DISEASE PROGRESSION
How Cardiometabolic Disease Develops
Cardiometabolic disease is not sudden. It is a slow, often silent progression that unfolds over decades. Understanding the stages matters because the earlier you intervene, the more of the pathway you can interrupt.
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The most important takeaway from this pathway is that the window for high-impact prevention is at Stage 1 and 2 before any standard test values are abnormal. This requires going beyond standard cholesterol panels to measure atherogenic particle number, insulin resistance, and inflammation directly in the proper context of the individual’s predisposition of age, gender, and ethnicity.
SCOPE OF THE PROBLEM
How Common Is Cardiometabolic Disease?
1 in 3
American adults have metabolic syndrome3
88%
of Americans with metabolic abnormalities don't know they have them4
#1
Cardiovascular disease remains the leading cause of death globally5
The scale of cardiometabolic disease makes it one of the defining public health challenges of our time. More than 37 million Americans have type 2 diabetes, and an estimated 96 million have prediabetes, with the majority undiagnosed.3 Cardiovascular disease causes roughly one in every three deaths in the United States.5
Perhaps most striking is how much of this disease burden exists invisibly. Because standard clinical testing doesn't measure insulin resistance or atherogenic particle number directly, many people with significant early-stage cardiometabolic disease receive normal test results, and possibly false reassurance, for years before a catastrophic event.
RISK FACTORS
Modifiable and Non-Modifiable Risk Factors
Cardiometabolic disease has both genetic and lifestyle components. Understanding which risk factors apply to you — and which are modifiable — is the foundation of a personalized prevention strategy.
Modifiable Risk Factors
Physical inactivity is the most powerful driver of insulin resistance and the most powerful intervention against it
Dietary pattern that includes excess refined carbohydrates, ultra-processed foods, and seed oils; insufficient protein and fiber
Excess visceral/abdominal adiposity
Poor sleep quality or insufficient sleep duration (independently associated with insulin resistance and inflammation)
Chronic psychosocial stress (elevates cortisol, which promotes visceral fat deposition and insulin resistance)
Smoking
Excessive alcohol consumption
Non-Modifiable Risk Factors
Age (cardiometabolic risk accumulates with age regardless of other factors)
Biological sex (men typically develop cardiometabolic disease earlier; women's risk rises sharply after menopause)
Family history of type 2 diabetes, heart disease, or hyperlipidemia
Ethnicity (South Asian, Hispanic, and Black populations have higher baseline risk for several cardiometabolic conditions)
Elevated Lipoprotein(a) which is a genetically determined lipid particle that confers independent cardiovascular risk. Learn more about high Lp(a).
Effective risk management requires understanding both. Non-modifiable factors establish your baseline risk level and inform how aggressively modifiable factors should be addressed. A person with family history of early heart disease and elevated Lp(a), for example, has strong reasons to manage every modifiable risk factor with clinical precision.
ADVANCED TESTING
The Biomarkers Used to Measure Cardiometabolic Risk
Standard cholesterol tests—total cholesterol, LDL-C, HDL-C, triglycerides—were designed decades ago and reflect the scientific understanding of that era. They remain marginally useful as a starting point, but they are insufficient for precision cardiometabolic risk assessment. But these basic labs regularly miss so much more context for identifying disease risk.
The following biomarkers, measured through advanced lipid and metabolic testing, provide a far more complete and accurate picture of cardiometabolic disease risk.
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LDL-P (LDL Particle Number) & ApoB
The count of atherogenic particles in your bloodstream. More particles mean more opportunities for arterial wall infiltration and plaque formation even when LDL cholesterol appears normal. ApoB measures the same concept with even greater accuracy, since it counts every atherogenic particle type (LDL, VLDL, IDL, Lp(a)).
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GlycA (Glycoprotein Acetylation)
A highly stable NMR-derived measure of chronic systemic inflammation. Unlike hs-CRP, which spikes with acute illness, GlycA reflects persistent inflammatory burden that drives atherosclerosis, insulin resistance, and long-term cardiovascular risk. Elevated GlycA (>400 µmol/L) is an independent risk factor for cardiovascular events, diabetes, and mortality.
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HbA1c & Fasting Glucose
Traditional markers of glycemic status. HbA1c reflects average blood glucose over the past 2–3 months and is the primary diagnostic criterion for prediabetes (5.7–6.4%) and type 2 diabetes (≥6.5%). Useful but lagging indicators, they become abnormal after significant insulin resistance and metabolic dysfunction have already developed.
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LP-IR Score (Lipoprotein Insulin Resistance)
A composite NMR-derived score that measures insulin resistance through the lens of lipoprotein metabolism — capturing the pattern of large VLDL, small LDL, and small HDL particles that characterize insulin-resistant states. LP-IR can detect insulin resistance up to 8 years before glucose or insulin values become abnormal.
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Lipoprotein(a) — Lp(a)
A genetically determined lipid particle that independently elevates cardiovascular risk and is almost never measured in routine care. Elevated Lp(a) is present in approximately 20% of the population and is not responsive to most standard interventions, making early identification essential for clinical decision-making. Lp(a) is highly under-measured in the US.
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Metabolic Syndrome Severity Score
A continuous score that quantifies the severity of metabolic syndrome based on your age, sex, and the five clinical criteria giving a more nuanced picture than the binary diagnosis. The Metabolic Syndrome Severity Score lets you track whether your metabolic health is improving or worsening over time.
These biomarkers don't work in isolation. Instead, they tell a complete story only when interpreted together, in the context of your personal clinical history, age, sex, ethnicity, family history, and existing conditions. This is the core rationale for a comprehensive, personalized Cardiometabolic Risk Assessment rather than one-off lab tests.
THE GAP IN STANDARD CARE
Why Standard Testing Often Misses Cardiometabolic Disease
In a typical clinical encounter, cardiometabolic risk assessment consists of: a standard lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides), a fasting glucose or HbA1c, and blood pressure measurement. This is roughly equivalent to using a weather vane to predict a hurricane.
There are two fundamental limitations:
1. LDL Cholesterol Frequently Misclassifies Risk
LDL-C measures the cholesterol content carried inside LDL particles, not the number of particles themselves. Particle count is what determines how much arterial wall infiltration occurs. In people with insulin resistance, it is common to have normal or even low LDL-C while having an elevated LDL particle number (LDL-P) or ApoB and correspondingly high cardiovascular risk. This discordance, like normal LDL-C but high ApoB or LDL-P, affects a large proportion of metabolically at-risk patients and is completely invisible to a standard lipid panel.
Conversely, someone with high LDL-C but a low LDL particle count may have lower actual cardiovascular risk than their cholesterol level suggests. The relationship between LDL-P and ApoB clarifies this further.
2. Insulin Resistance Is Invisible to Standard Testing Until It's Late
Fasting glucose and HbA1c don't become abnormal until the pancreas can no longer compensate for insulin resistance, which typically takes years or decades. By the time a patient receives a prediabetes or diabetes diagnosis, they may have had significant metabolic dysfunction (and accumulating cardiovascular risk) for a decade. The LP-IR score, HOMA-IR, and other insulin resistance measures can detect this dysfunction years before glucose values rise.
The result of these usual testing limitations is a clinical blind spot: the patients most at risk for cardiometabolic events are often the ones receiving false reassurance from standard labs. Advanced biomarker testing, particularly in complete personalized context, closes this gap.
PRECISION ASSESSMENT
What a Comprehensive Cardiometabolic Risk Assessment Looks Like
A precision cardiometabolic risk assessment integrates advanced biomarkers with personal clinical data to answer three specific questions with quantified, individualized precision:
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The Precision Health Reports Cardiometabolic Risk Assessment is built on this framework. It combines your advanced lipid panel results (ApoB, lipids, Lp(a)), insulin resistance, HbA1c, fasting glucose, blood pressure, personal risk factos, and clinical history into a clinician-ready report with guideline-based, individualized risk-reduction targets.
The assessment also incorporates noninvasive imaging results when available, such as a Coronary Artery Calcium (CAC) score or Carotid Intima-Media Thickness (CIMT), which provides direct anatomical evidence of subclinical atherosclerosis and can significantly refine risk stratification. Knowing whether or not there is existing evidence of arterial plaque is extremely important to properly identify and manage future risk.
TESTING OPTIONS
Comparing Cardiometabolic Testing Approaches
Not all cardiometabolic testing is equal. The table below compares what different testing approaches measure and what they miss.
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For those evaluating other testing options, see how Precision Health Reports compares to Function Health and Boston Heart Labs.
COMMON QUESTIONS
Frequently Asked Questions
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Cardiovascular disease (CVD) refers specifically to conditions of the heart and blood vessels — coronary artery disease, heart attack, stroke, and peripheral artery disease. Cardiometabolic disease is a broader term that encompasses cardiovascular disease alongside metabolic conditions: type 2 diabetes, insulin resistance, metabolic syndrome, and obesity. The key distinction is mechanistic: cardiometabolic disease recognizes that cardiovascular and metabolic disease are not separate problems — they develop along the same biological pathway and must be managed together.
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In its early stages, particularly insulin resistance and metabolic syndrome, cardiometabolic disease is substantially reversible through lifestyle intervention: resistance and aerobic exercise, dietary change, weight reduction, and improved sleep. More advanced stages involving established ASCVD or type 2 diabetes can be managed and their progression arrested, but existing arterial damage is not fully reversible. This is why early identification through advanced biomarker testing, before clinical thresholds are breached, represents the highest-value intervention point.
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A cardiometabolic risk score integrates multiple biomarkers like atherogenic particle number, insulin resistance, inflammation, glycemic markers, blood pressure, and clinical history, into a quantified, personalized probability of experiencing future cardiovascular or metabolic disease events. Unlike single biomarker values or population-average reference ranges, a proper cardiometabolic risk score is individualized to your age, sex, ethnicity, and clinical profile. It tells you not just whether individual values are "high" or "low," but what your actual integrated risk looks like and which of your risk factors should be addressed first.
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Fasting glucose and HbA1c are late-stage indicators that don't become abnormal until the pancreas can no longer compensate for insulin resistance — which may be years or decades after resistance begins. Earlier detection is possible through the LP-IR score, a composite measure derived from the NMR Lipoprofile that detects the characteristic lipoprotein pattern of insulin resistance. LP-IR has been shown to predict the development of type 2 diabetes up to 8 years before glucose-based measures become abnormal. HOMA-IR (from fasting glucose + fasting insulin) is another option, though less sensitive than LP-IR. See the full comparison of insulin resistance measures.
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No, metabolic syndrome is one component of cardiometabolic disease, not synonymous with it. Metabolic syndrome is defined by the presence of three or more of five specific clinical criteria: abdominal obesity, elevated triglycerides, low HDL, elevated blood pressure, and elevated fasting glucose. Cardiometabolic disease is a broader concept that includes metabolic syndrome but also encompasses established ASCVD, type 2 diabetes, insulin resistance (which can be present without meeting metabolic syndrome criteria), and other related conditions. Metabolic syndrome is better understood as a clinical marker that a person is significantly advanced along the cardiometabolic disease pathway.
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Lipoprotein(a), or Lp(a) AKA “L P little A”, is a lipoprotein particle structurally similar to LDL but with an additional protein called apolipoprotein(a) attached. It is strongly atherogenic, pro-thrombotic, and genetically determined, meaning it cannot be meaningfully modified by lifestyle or most existing pharmacological interventions. Elevated Lp(a) affects approximately 1 in 5 people and independently increases risk for heart attack, stroke, and aortic valve disease. Despite this, it is almost never measured in standard clinical care. Identifying elevated Lp(a) early allows for more aggressive management of all other modifiable risk factors, which is the most effective current strategy for high-Lp(a) individuals. Learn more about high Lp(a).
EVIDENCE BASE
References & Further Reading
Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc Diabetol. 2018;17:83. doi:10.1186/s12933-018-0728-6
Boren J, Chapman MJ, Krauss RM, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights. Eur Heart J. 2020;41(24):2313–2330.
Centers for Disease Control and Prevention. National Diabetes Statistics Report. 2023. cdc.gov
Araújo J, Cai J, Stevens J. Prevalence of optimal metabolic health in American adults: National Health and Nutrition Examination Survey 2009–2016. Metab Syndr Relat Disord. 2019;17(1):46–52.
Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics — 2023 Update. Circulation. 2023;147:e93–e621.
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC Guideline on the Management of Blood Cholesterol. J Am Coll Cardiol. 2019;73(24):e285–e350.
Diabetes Prevention Program Research Group. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. N Engl J Med. 2002;346:393–403.
Mora S, Otvos JD, Rifai N, et al. Lipoprotein particle profiles by NMR compared with standard lipids and apolipoproteins in predicting incident CVD in women. Circulation. 2009;119:931–9.
Jeyarajah EJ, Cromwell WC, Otvos JD. Lipoprotein particle analysis by NMR spectroscopy. Clin Lab Med.2006;26(4):847–70.
Ballout RA, Remaley AT. GlycA: A new biomarker for systemic inflammation and CVD risk assessment. J Clin Lipidol.2020;14(5):623–636.
Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: evidence from genetic, epidemiologic, and clinical studies. Eur Heart J. 2017;38:2459–72.