Cardiovascular conditions are one of the most common disorders of modern times.  Testing for cholesterol as a potential modifiable risk factor for heart disease is a common part of many functional medicine providers’ clinical practices. Recently, at Rupa Health we wrote about the latest innovations in cholesterol testing such as measuring ApoB-containing lipoproteins and genetic differences in intracellular cholesterol production or gut absorption. In this article we will go beyond cholesterol to discuss the other critical tests for heart health.

Fibrinogen Blood Test

Fibrinogen is an important component of blood clots. In healthy individuals, it’s detectable in plasma at fairly high levels (2-5 mg/mL) but can exceed 7 mg/mL during acute inflammation. The challenge with fibrinogen is that it can accumulate on the endothelial lining of arteries and contribute to coronary artery disease. In fact, high fibrinogen levels and are as predictive as elevated cholesterol.

Another study found a pronounced positive association between initial plasma fibrinogen concentrations and later development of heart attacks in 40 to 69-year-old men who were free from overt coronary heart disease at baseline. In men who had high cholesterol, there was a six times greater frequency of heart attacks in those with high plasma fibrinogen levels compared to those with low levels. Men with high systolic blood pressure and high fibrinogen had a 12 times greater occurance of heart attacks compared with men that had high systolic blood pressure and low fibrinogen levels.

The authors wrote, “In multivariate models plasma fibrinogen was a highly significant and independent explanatory variable, at least as important as serum cholesterol, blood pressure or cigarette smoking. These results suggest that high plasma fibrinogen levels are an important coronary risk factor and should be included in profiles used to identify those at high risk of heart attacks.”

Furthermore, fibrinogen and fibrin have been found in atherosclerotic blood vessels in .  In normal aortic samples, the presence of fibrinogen and fibrin was rare. Conversely, in early atherosclerotic plaques, scientists found fibrinogen and fibrin in the intima and subintima layers, as well as around foam cells and in regions of loose connective tissue. And in advanced lesions, fibrinogen:fibrin immunoreactivity occurred around macrophages and smooth muscle cells as well as in places where cholesterol crystals and calcium were deposited.

Fibrinogen testing through a simple blood draw can measure plasma levels of this cardiovascular risk marker. We’ll cover some strategies for lowering elevated fibrinogen levels later in this article.

CRP Testing

High-sensitivity C-reactive protein (hs-CRP) is a well-known marker of inflammation and increasing evidence indicates that inflammation plays a central role in cardiovascular conditions. CRP is synthesized as part of the acute-phase response to inflammation, infection, and tissue injury.

Across various countries and ethnicities, higher hs-CRP levels correlate with worse cardiovascular risk. For example, higher levels of hs-CRP in Japanese men and women are associated with increased cardiovascular mortality. In the United States, hs-CRP levels were linked to cardiovascular mortality in European Americans with type 2 diabetes. Another of male physicians in the United States found that higher CRP levels were associated with heart attacks and strokes. Elevated levels of hs-CRP correlate with worse cardiovascular outcome after acute coronary syndrome, and hs-CRP may be involved in the initiation and development of atherosclerotic plaque.

This marker can also be evaluated through an easy blood test. Because hs-CRP is non-specific, elevated levels should be interpreted in combination with a physical exam and review of medical history. Many scientists believe that measuring CRP levels can have great clinical usefulness and contribute significantly to management of disease. One group of researchers even compared it to measuring a patient’s temperature, which is equally nonspecific, and still of clinical utility.

HbA1c

Hemoglobin A1C (HbA1c) levels are often measured in those with type 2 diabetes and can also be important marker for CVD risk. Evidence indicates that as HbA1c levels decline in type 2 diabetics so does the risk of developing coronary heart disease and all-cause mortality. Indeed, reducing HbA1c levels in type 2 diabetics can decrease the absolute risk of developing coronary heart disease by 5% – 17%. And yet other researchers have found that each 1% increase of HbA1c was linked to a greater increase in coronary heart disease risk in diabetic patients.

Atrial Fibrillation Test

Atrial fibrillation is characterized by irregular electrical activity of the atria that causes an irregular heart rhythm and increases chances of clot formations in the heart. Sadly, one in ten individuals over the age of 80 have atrial fibrillation, which leads to significant morbidity and can predict mortality independent of other risk factors. Interestingly, individuals with certain genotypes have an increased risk of atrial fibrillation. The 4q25 gene locus on chromosome 4, adjacent to the PITX2 gene, is a transcription factor required for cardiac development and left-right asymmetry of the heart, and for normal sinus node formation.

has two 4q25 variants (rs2200733 and rs10033464), which have been linked to a significant 1.4-1.5-fold increase in the risk for atrial fibrillation. Approximately 35% of people of European descent have at least one of those variants. This risk is especially notable in those over age 60. The Boston Heart Diagnostics offers a blood draw serum test that measures atrial fibrillation genotypes in serum.

MTHFR Testing

Methylenetetrahydrofolate reductase—MTHFR for short—is an enzyme involved in the methylation process. Its primary role is to convert folate or folic acid into the active form (5-MTHF). When MTHFR is working properly, levels of an amino acid known as homocysteine stay balanced. However, many people have a variant (also called a polymorphism) in the MTHFR gene, which can impair the MTHFR enzyme’s function. This also leads to high levels of homocysteine, which in turn makes people more vulnerable to a number of diseases, including heart disease. can increase thrombogenicity, oxidative stress, and endothelial dysfunction. It is also a risk factor for developing coronary artery disease.

The two well-known variants of the MTHFR gene are C677T and A1298C. Depending upon whether a person has one or two copies of the C677T variant, levels of the MTHFR enzyme activity can drop by 33% to 35% or 70% to 75% respectively. Two copies of the A1298C variant can cause MTHFR enzyme activity to fall by 39%. Ordering MTHFR testing and plasma homocysteine together can offer insight into whether a patient should focus on dietary supplements and other strategies to lower homocysteine and to make up for methylation deficits. Read more about MTHFR in our previous post: “6 Surprising Reasons to Test for the MTHFR Mutation.”

Vitamin D Blood Test

Roughly 30% to 50% of people have vitamin D deficiency, defined as less than 30 ng/mL. Vitamin D has a well-known role in calcium metabolism, but lately there has been a greater appreciation of vitamin D’s potential role as a cardiovascular disease risk factor. Several epidemiological and clinical studies have found a close correlation between low vitamin D levels and cardiovascular conditions, including coronary artery disease, heart failure, and atrial fibrillation and vitamin D deficiency is linked to increased morbidity, mortality, and recurrent cardiovascular events.

This cardiovascular connection makes sense given vitamin D’s role in certain aspects of heart function. Cardiomyocytes, smooth muscle cells, fibroblasts, and vascular endothelial cells all have vitamin D receptors. In addition, 1α-hydroxylase, an enzyme that modulates the synthesis of the active form of vitamin D is also found in these cardiac cells. And so Vitamin D testing is important not only for identifying deficiency but also as an assessment of CVD risk. Functional medicine providers usually like to see vitamin D levels between 50 ng/mL and 80 ng/mL.

Strategies to Improve Cardiovascular Risk Markers

Turmeric

Turmeric (Curcuma longa) , rich in the compound curcumin, has been found to decrease fibrinogen levels. In a study, participants high fibrinogen levels (on average over 350 mg/dL) treated wih turmeric tablets containing 10 mg of curcumin for 15 days showed decreased fibrinogen levels (down to 240 – 290 mg/dL). One of the subjects who had a baseline fibrinogen level of 809 mg/dL had their level fall down to 241 after turmeric supplementation.

Magnesium

Magnesium supports healthy blood pressure levels and a healthy heart rhythm.  It is often used intravenously in the emergency room to stabilize heart rhythm in patients undergoing acute atrial fibrillation.

Active Folate and B Vitamins

In people who have the MTHFR polymorphism, supplementing with an active form of folate known as 5-MTHF can lead to better utilization of folate and a reduction in homocysteine. Other B vitamins such as B6 and B12 are known for their ability to lower homocysteine levels.

Vitamin D

The importance of Vitamin D in heart health was discussed earlier in this article. Suggested maintenance doses typically range between2,000 – 3,000 IU/day for healthy adults. Vitamin D testing can be used as a guide to further determine appropriate doses of vitamin D for each individual.

Cinnamon and Chromium

Cinnamon improves HbA1c as well as other aspects of glycemic control, especially in people with a high body mass index. Chromium picolinate has similar beneficial effects on glycemic control and can significantly reduce HbA1c.

Weight Loss

And of course, weight loss in those who need it can lead to improvements in cardiometabolic health. Weight loss can reduce insulin resistance and HbA1c. For every 2.20 pounds lost, HbA1c declines by a mean of 0.1 percent. Weight loss results in a greater HbA1c reduction in people who have poor glycemic control compared with people who have better glycemic control. There is also a significant positive correlation between baseline CRP levels and BMI with weight loss leading to lower CRP concentrations.

Conclusion

Although cholesterol testing can be clinically useful, there are other cardiovascular risk markers that can lead to meaningful diagnosis and effective treatment. Fibrinogen, CRP, HbA1c, homocysteine/MTHFR, testing for atrial fibrillation genotypes, and vitamin D testing can all provide a more complete picture than cholesterol testing alone.

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Rupa Health helps practitioners take the guesswork out of the labwork experience. Clinicians can order, track, and get access to 20+ lab companies in one place, at no extra cost. Choose from a variety of laboratories that test for these important heart markers.

Access Medical Laboratories

Ayumetrix

BioReference Laboratories

BostonHeart Diagnostics

Cell Science Systems

Genova Diagnostics

Great Plains Laboratory

SpectraCell Laboratories

US Biotek

Vibrant America

ZRT

Fibrinogen, hs-CRP, and homocysteine are available as serum or plasma specimens. HbA1c can be measured with whole blood or blood spot. MTHFR can be measured using whole blood, buccal swab, or blood spot. BostonHeart Diagnostics’ atrial fibrillation risk test requires a serum specimen.

Take a look at Rupa’s Live Classes for practitioners and Functional Medicine Lab Testing articles.