Modifiable Factors Influence Non-modifiable Factors for Cardiovascular Health?

The scientific community continues its full force swing at reducing cardiovascular disease risk. In the Scientific Session titled “Microbiome in Cardiovascular Disease,” the complexity of accounting for human variation was the theme. The important difference and interactions between non-modifiable (genetics) and modifiable (diet, exercise, smoking, etc..) factors were presented. Dr. Katherine Tucker opened up the session by highlighting work from Thanassoulis et. al., 2012, which identified 13 single nucleotide polymorphisms (SNPs) to generate a genetic risk score (GRS) to predict cardiovascular events and coronary artery calcium (CAC). Single nucleotide polymorphisms are the most common type of genetic variation among people and are used to help quantify the variation in individuals (1). The CAC score comes from a test that quantifies the amount of calcium accumulation in the walls of the coronary arteries. A lower score represents a greater risk and a lower score relates to a lower risk of heart disease. Dr. Tucker went on to explain the genetic risk is influenced by individual environmental factors (i.e. smoking, exercise, and diet) (2). Recent data from the CARDIA study supports this in reporting that, “low-carbohydrate diets at a younger age is associated with an increased risk of subsequent CAC progression, particularly when animal protein or fat are chosen to replace carbohydrates. (3).”

Figure 1 source:

The changes in macronutrient content in a diet is related to what happens in the gut. Within the gut, there are trillions of bacteria that make up a microbiome. An individual microbiome modulates the immune system and metabolic processes. The microbiome influence on human health is so pronounced in that it actively reprograms the genome in response to the environment, changing the bacteria phyla ratios that lead to down-stream effects that could influence cardiovascular health (Figure 1) (2). Dietary fiber and prebiotic consumption are two components that modulate the composition of the gut microbiome (Figure 2) (4). Also, there is some great news for you Kombucha fans out there! Fermented foods have some benefits for the gut.

Figure 2. Source:

Bhat and Kapila 2017 further highlight diet in a review stating “The composition of the gut microbiota has a tremendous influence on host metabolism.” Perhaps specific dietary interventions can reduce the risk of cardiovascular disease with the focus on obtaining an optimal microbiota composition. Zhang et. al., 2020, showed how detrimental diets with contain highly processed foods can be the bacteria in our gut (Figure 3) (5).

Figure 3. Source:

To further highlight how much people differ from one another, Dr. Tang from the Cleveland Clinic explained only 37% of the gut is actually shared between twins. In addition, there are significant diurnal variations in response to meals consumed among people. The work presented the relationship between microbiota and trimethylamine (TMA)/trimethylamine–N-oxide(TMAO) generation. Elevated TMAO levels predict major adverse cardiac events like death, myocardial infarction (MI), and stroke (Figure 4) (6). Dr. Tang explained that risk is highest with people who displayed the highest baseline levels of two TMAO precursors choline or L-carnitine, while some may show no risk with higher levels. Dr. Tang emphasized the variation again among individuals.

Figure 4. Source: Tang, W. W., & Hazen, S. L. (2014)

We are only scratching the surface with the modifiable risk factors for heart disease. Specifically, the gut shows an area rich for investigation. The gut microbiota contributes to human physiology and diseases and it is something to be excited about for biomedical researchers.



  1. Thanassoulis G, Peloso GM, Pencina MJ, Hoffmann U, Fox CS, Cupples LA, Levy D, D’Agostino RB, Hwang SJ, O’Donnell CJ. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet. 2012 Feb 1;5(1):113-21. doi: 10.1161/CIRCGENETICS.111.961342. Epub 2012 Jan 10.
  2. Mohd Iqbal Bhat, Rajeev Kapila, Dietary metabolites derived from gut microbiota: critical modulators of epigenetic changes in mammals, Nutrition Reviews, Volume 75, Issue 5, May 2017, Pages 374–389,
  3. Gao, J. W., Hao, Q. Y., Zhang, H. F., Li, X. Z., Yuan, Z. M., Guo, Y., … & Liu, P. M. (2020). Low-Carbohydrate Diet Score and Coronary Artery Calcium Progression: Results From the CARDIA Study. Arteriosclerosis, Thrombosis, and Vascular Biology, ATVBAHA-120.
  4. Genelle R Healey, Rinki Murphy, Louise Brough, Christine A Butts, Jane Coad, Interindividual variability in gut microbiota and host response to dietary interventions, Nutrition Reviews, Volume 75, Issue 12, December 2017, Pages 1059–1080,
  5. Zefeng Zhang, Sandra L Jackson, Euridice Martinez, Cathleen Gillespie, Quanhe Yang, Association between ultraprocessed food intake and cardiovascular health in US adults: a cross-sectional analysis of the NHANES 2011–2016, The American Journal of Clinical Nutrition,
  6. Tang, W. W., & Hazen, S. L. (2014). The contributory role of gut microbiota in cardiovascular disease. The Journal of clinical investigation, 124(10), 4204-4211.


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