Biomarkers for Cardio Health
By Densie Webb, PhD, RD
Vol. 25 No. 2 P. 18
Learn more about the most common and newly studied determinants that help predict heart disease risk and better diagnose and manage patients.
Heart disease, which encompasses several types of heart conditions, is the leading cause of death for men and women in the United States. Despite improvements and advances in diagnosis and treatment, heart disease stubbornly remains the number one cause of death in the United States and globally. The most common type of heart disease in this country is coronary artery disease, which affects blood flow to the heart.1 According to Cleveland Clinic, almost one-half of all adults in the United States have at least one form of heart disease.2 In addition, a recent study published in the journal Circulation found that less than one-third of patients who experienced a type 2 heart attack (due to weakened heart muscles) were undiagnosed.3 Type 1 heart attack is due to a blood clot (thrombosis) or other blockages in blood flow through an artery in the heart.
Several biomarkers are available to assess heart disease risk for those who already have experienced a cardiac event, as well as those who are undiagnosed. However, biomarkers for heart disease are complex. Typically, each biomarker has several subtypes that either may protect against or promote heart disease. While several biomarkers of heart disease risk have been identified, many more are being researched. These circulating biomarkers play a crucial role in the risk stratification, diagnosis, and management of patients with heart failure and acute coronary syndrome.
Commonly Tested Cardiac Biomarkers
Some of the most common biomarkers evaluated include troponin, ceramides, coronary calcium scans, HDL cholesterol (HDL-C), and LDLs.
Higher levels of troponin in the blood indicate heart damage, and measuring this biomarker can help determine the severity of a heart attack. Troponin is a protein involved in muscle contraction and is found in the muscles of the heart. A recent study found that one-half of all elevated cardiac troponin levels are due to type 2 heart attacks or myocardial injury. According to the Cleveland Clinic, there are two forms related to the heart: troponin I and troponin T). Normally, troponin stays inside the heart muscle’s cells, but damage to those cells causes troponin to leak into the blood. According to Lena Beal, MS, RDN, LD, a cardiovascular dietitian at Fuqua Heart Center of Atlanta and a spokesperson for the Academy of Nutrition and Dietetics, “Troponin levels can rise for up to 12 hours after a heart attack.”
Newer versions of this test are much more sensitive and can pick up far smaller amounts of this protein in the blood, which can speed up the process of diagnosing a heart attack. This test is useful when other tests are inconclusive or when a patient has vague symptoms. Also known as a cardiac troponin test, the blood test uses the abbreviations cTn, cTnI, or cTnT, depending on the specific type of test. Some versions of this test can detect only one type of troponin.4 A 2020 study found that a healthful diet, regardless of macronutrient content, lowered troponin levels in adults with elevated blood pressure.5
Elevated ceramides are associated with insulin resistance, type 2 diabetes, hypertension, and CVD. Ceramides are complex lipids that play a central role in cell membrane integrity, cellular stress response, inflammatory signaling, and apoptosis. When dyslipidemia and calorie excess are present, ceramides accumulate in tissues. LDLs transport ceramides in the blood and raise the rate at which LDLs infiltrate vessel walls and increase the formation of arterial plaque. Inflammation stimulates the synthesis of ceramides via inflammatory cytokines. According to Jeffrey W. Meeusen, PhD, codirector of cardiovascular laboratory medicine in the department of laboratory medicine and pathology at the Mayo Clinic in Rochester, Minnesota, a ceramide risk score incorporates the values from six ceramide results. The potential risk attributable to ceramides is provided on a 12-point scale. Patients with a score of 10 to 12 are thought to have a four- to six-fold increase in risk of cardiac events compared with patients with a score of two points or less. Ceramide concentrations can be significantly decreased by caloric restriction, gastric bypass, aerobic exercise, and statin therapy.6
Coronary Calcium Scan
A coronary calcium scan provides an image of calcification or plaque in the coronary arteries. The results are given as a number, known as an Agatston score. A calcium scan can be used when heart disease risk isn’t clear. However, calcium scans aren’t recommended as the sole predictor of heart disease risk and should be combined with findings from other tests. According to the Mayo Clinic, the interpretation of calcium scans is as follows:
• A score of zero means no calcium is seen in the heart and predicts a low risk of CVD for the subsequent 10 years if no chronic inflammatory condition exists.
• A score of 100 to 300 means there are moderate plaque deposits and is associated with a relatively high risk of heart attack or other heart diseases.
• A score greater than 300 indicates a very high to severe risk of heart disease and heart attack.
Both the American Heart Association and American College of Cardiology recommend calcium scans to identify patients who will potentially benefit from statin therapy. A calcium scan delivers about the same amount of radiation as a mammogram and may cost anywhere from $100 to $400, with insurance coverage varying among carriers.7
Lower HDL-C levels are a major factor in raising CVD risk, according to several studies. HDL is a complex form of cholesterol with differences based on size, density, charge, chemical composition, and functionality. HDLs are responsible for the transport of 20% to 30% of circulating lipids in blood plasma. HDL-C has long been tagged as “good” cholesterol associated with a reduced risk of CVD. However, some research suggests that a single measurement of HDL-C isn’t the most accurate marker for the risk of coronary artery disease.8 HDL’s benefits may be due to the levels of subcategories of HDL particles rather than the total HDL-C level. For instance, smaller, denser, protein-rich HDL particles (HDL3) are more atheroprotective than large, buoyant, cholesterol-rich particles. HDL particles also have been found to possess vascular effects, as well as antiatherogenic properties, such as a protective effect against inflammation, oxidation, angiogenesis, and glucose homeostasis.9
While reduction in HDL-C generally is related to an increased risk of CVD, very high levels of HDL-C also may be associated with an elevated risk, suggesting a U-shaped relationship between HDLs and CVD.10,11 In addition, clinical trials using pharmacotherapies to increase HDL-C concentrations haven’t found an association with a reduction in atherosclerotic CVD events.
A recent study found that while low levels of HDL-C were associated with an increased risk of coronary heart disease in white adults, the same wasn’t found among Black adults, even after adjusting for clinical and behavioral factors. The authors suggested that the race-dependent findings bring into question the usefulness of risk prediction equations that reward high HDL-C and penalize low HDL-C.12 According to the authors, “Our current understanding of how HDL contributes to coronary heart disease is primarily shaped by the Framingham Heart Study, where all cohorts are 100% white American.”
In healthy people, the established low-risk levels of HDL-C are 40 mg/dL in men and 50 mg/dL in women. Women tend to have HDL-C levels that are 10% to 20% higher than men. There’s a paradigm shift from focusing on HDL quantity to HDL quality and functionality.13 A healthful diet and physical activity have long been shown to raise HDL-C levels.14
Making up the majority of cholesterol in the blood, LDLs transport cholesterol from the liver to the body’s tissues.7 Levels of LDL cholesterol (LDL-C), a component of LDL, have long been considered a major modifiable risk factor for CVD. A recent systematic review and meta-analysis of 21 studies cast doubt on the efficacy of lowering LDL-C with statins to reduce risk when it found only modest benefits from taking statins.15 Lipoprotein(a) is a type of LDL that may be more reflective of CVD risk than total LDL levels or measurement of LDL-C. There’s evidence that excess lipoprotein(a) can independently cause hardening of the arteries and that elevated lipoprotein(a) increases the risk of heart attack by 50%, and almost doubles the risk of having a stroke.16
There’s a large body of evidence showing that diet affects LDL-C levels. Two recent studies found that specific foods may be most effective. Researchers in Sweden found strong evidence that foods high in unsaturated fats, low in saturated and trans fatty acids, and high in plant sterols/stanols and soluble fiber caused a moderate reduction in LDL-C. Unfiltered coffee, such as French press or Turkish coffee, caused a moderate to large increase in LDL cholesterol.17 Another study specifically looked at consuming one cup of beans (daily rotation of black, navy, pinto, dark red kidney, and white kidney) for 29 days in a multicenter, randomized, crossover study and found that LDL-C levels were reduced in adults with elevated LDL-C levels.18 In healthy people, the recommended target levels of LDL are 130 mg/dL for men and women. The optimal level for people with diabetes or heart disease is 100 mg/dL.
Beal offers the following dietary recommendations for reducing biomarkers that indicate high risk of heart disease:
• the DASH diet, which is rich in fruits, vegetables, whole grains, and low-fat dairy products;
• Mediterranean diet patterns, which are rich in fish, pulses, whole grains, vegetables, fruits, and healthful fats;
• vegetarian/vegan diets, which are rich in plant foods; and
• moderation in alcohol intake (men no more than two drinks per day; women no more than one drink per day).
Biomarkers With Potential
In addition to the most common biomarkers of cardiovascular health, there are several being studied for their role in predicting heart disease risk. While some currently are used in only research, any one of them can become routine biomarkers in the future.
Research has found that urinary levels of nonconjugated carnosine, carnosinepropanal, and carnosine-propanol may be useful biomarkers for assessing CVD risk, particularly among those with type 2 diabetes. Carnosine is a naturally occurring dipeptide found in the heart, as well as skeletal muscle and brain tissues.19
Higher levels of calprotectin have been associated with smoking, a cause of inflammation, and are linked with CVD in patients with type 2 diabetes. Calprotectin is a protein secreted by leukocytes and is regulated in response to inflammation.19
This hormone has been shown to have a protective effect against CVD, by reducing inflammation and fibrosis. Low levels of adiponectin have been shown to be associated with obesity-linked cardiovascular disorders. However, in some cases, higher levels of adiponectin are associated with no beneficial effects and even increased mortality.20 This paradoxical pattern is being studied for its practical application.
Circulating levels of leptin, a protein secreted primarily from adipose tissue, are related to the amount of adipose tissue mass. The higher the fat mass, the higher the circulating levels of leptin. While it has been established that low levels of leptin are correlated with poor outcomes in CVD, research suggests that the highest levels also are associated with increased CVD risk. The mechanism(s) responsible for this seemingly paradoxical relationship to CVD aren’t fully understood.20
Clients and patients with any of the risk factors below are most likely to develop CVD and may be candidates for one or more biomarker screenings:
• tobacco use (including vaping);
• type 2 diabetes;
• family history of heart disease;
• lack of physical activity;
• having excess weight or obesity;
• diet high in sodium, sugar, and fat;
• overuse of alcohol;
• misuse of prescription or recreational drugs;
• preeclampsia or toxemia;
• gestational diabetes;
• chronic inflammatory or autoimmune conditions; and
• chronic kidney disease.
The field of biomarkers for heart disease is complex and ever evolving. Beal says most physicians share only lipid levels and calcium scores with RDs. But she says, “RDs would benefit from keeping current with the guidelines and overall cardiac risk factors, and if one or more risk factors is present, [they should] provide diet counseling that promotes cardiac risk reduction.”
— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas
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2. Cardiovascular disease. Cleveland Clinic website. https://my.clevelandclinic.org/health/diseases/21493-cardiovascular-disease. Updated September 1, 2022. Accessed November 20, 2022.
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6. Ceramides: a class of lipids with links to heart disease. Mayo Clinic website. https://www.mayoclinic.org/medical-professionals/cardiovascular-diseases/news/ceramides-a-class-of-lipids-with-links-to-heart-disease/mac-20429577. Published January 20, 2018. Accessed November 18, 2022.
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18. Doma KM, Dolinar KF, Ramdath D, Wolever TMS. Canned beans decrease serum total and LDL cholesterol in adults with elevated LDL cholesterol in a 4-wk multicenter, randomized, crossover study. J Nutr. 2021;151(12):3701-3709.
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