In today’s age of information, the mysteries of health can be unraveled through growing evidences surrounding health biomarkers and their indicators of health. Health check ups are often done on a yearly basis, but do we actually understand the results of our own health report? In this article, we aim to dispel the elusiveness of health biomarkers and spotlight some of the key indicators of health relating to health span.

Serum Biomarkers

A biomarker is defined as a measurement of an indicator to biological processes, pathogenic processes or responses to an intervention (FDA-NIH Biomarker Working Group, 2016). It gives a doctor information about our health targeted to a specific function. In the realm of health span and large cohort statistics, clear evidences could be drawn with respect to health outcomes. According to a large cohort study Li et al. (2021), higher circulating levels of:

Glycated haemoglobin (HbA1c) – The measure of glucose level in bloodstream due to glycation of glucose onto haemoglobin protein present in our blood. Increased glucose levels can therefore be reflected through blood by measure of A1c levels (Eyth & Naik, 2023). HbA1c is also used as a measure for diabetes. 

Fasting Blood Glucose (FBG) – Measured several hours eating, giving a more accurate view on one’s glucose levels. High fasting blood glucose above 6.5% is also an indication of insulin resistance or diabetes (Cronkleton, 2024).

C-reactive Protein (CRP) – CRP is released by our liver into the bloodstream during inflammation, in which high levels of CRP might an indication of existing acute inflammation to a bacterial infection or chronic inflammation due to existing medical conditions. 

Triglycerides (TG) – A type of lipid that is stored when there is excess calories consumption or also from the food we eat. High TG can put us at risk of heart and vascular diseases such as heart attack and stroke. High TG can be caused through unmanaged diabetes, high sugar & saturated fat diet, excessive alcohol use, obesity, inflammatory diseases, lack of physical activity, or smoking (Cleveland Clinic, 2023).

were indicative of lower health span. Triangulating with other studies, similar biomarkers measured also suggest the importance of glycemic control through the indicators of HbA1c and FBG. Among the glycemic, lipid, and inflammatory markers discussed above, glucose control has the strongest influence over our health span (Li et al., 2021). Thus, it should be prioritised for intervention when it comes to boosting health outcomes. It comes without a surprise, in which high blood glucose is associated to increased risks of several chronic conditions, such as cancers (Boyle et al., 2013) (Liao et al., 2015) (Han et al., 2017), cardiovascular (Sarwar et al., 2010) and neurodegenerative diseases (Chatterjee et al., 2016). Figure 1 below illustrates the associating Hazard Ratio (HR) to respective serum biomarkers at a 95% confidence interval.

Figure 1: Association of serum biomarker to health outcomes, based on 2 independent large cohort studies (Li et al., 2021)

This is one of the primary reason most public health policies involved a cultivation of awareness and public intervention towards diabetes, commonly known as the “war on diabetes”. Fortunately for most of us, it can be intervened through lifestyle modifications such as diet and physical activity (Mehta & Myrskylä, 2017). Conversely, there are interestingly biomarkers that poised moderate to strong evidences associating to health span enhancement. Figure 1 above illustrates statistical significance from HDL-C, Apolipoprotein A1 (ApoA1), and Total Cholesterol (TC), in which they have shown positive correlation to increased health span.

HDL-C – High density lipoproteins are involved in the function of transporting excess cholesterol from rest of body back to the liver, and thus often referred to as the “good cholesterol” (Chiesa & Charakida, 2019).

ApoA1 – A component of HDL-C, it plays a vital role in cardiovascular diseases (CVD) reversal and cholesterol regulation. Furthermore, ApoA1 contributes to health in various influencing factors, including immunity, inflammation, apoptosis, viral, bacterial infection (Mangaraj et al., 2016).

What about Total Cholesterol?

How did Total Cholesterol end up as a positive association to health span? Up to today, reduction of TC has often been part of public health campaigns with the commonly accepted notion of “the lower, the better” in terms of overall cholesterol management. This is largely supported through statin trials in which reduces mortality from ischaemic heart disease (IHD), hence supporting the movement of cholesterol lowering drugs such as statin that helps to reduce risk of CVDs (Yi et al., 2019). However, it was found over a large cohort study of 12 million Korean adults followed up over a mean of 10.5 years, that TC follows a U-shape curve in terms of mortality hazard ratio.

Figure 2: TC measure with respect to mortality hazard ratio (Yi et al., 2019)

Figure above denotes the result of large cohort analysis on TC which signals a curve representing an ideal TC range. Interestingly, Yi et al. (2019) called out the ideal range between 210-249 mg/dL. According to the National Cholesterol Education Program (NCEP) Expert Panel (2002), this TC range would fall under borderline high to high range relating to IHD risk. However considering an all-cause mortality ratio including cancers, TC consistently conforms to a U-shape curve in terms of its association to hazard risk. Nevertheless, the general consensus lies in achieving a balance when it comes to lifestyle biomarkers. The reputation of cholesterol goes beyond cardiovascular diseases impact, it is in fact needed by our bodies for cellular function, hormones, bile and vitamin D production (Fletcher, 2022). 

Ultimately, health span hinges on expanding our disease-free years throughout our lifespan. Independent studies have come to a similar conclusion on health span termination commonly diagnosed through cancer, diabetes and myocardiac infarction (Li et al., 2021). Let us aim towards increasing our disease-free years as we strive to expand health, by holding ourselves accountable through annual health screening, and speaking to your doctor on health risks associating to blood results. This article touches on key serum biomarkers related to overall health span, with an added spotlight on glucose & diabetes control which shows a strong association to our overall well-being.

References

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Li et al. (2021). Clinical biomarkers and associations with healthspan and lifespan: Evidence from observational and genetic data. EBioMedicine, 66: 103318. doi: 10.1016/j.ebiom.2021.103318

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Cleveland Clinic. (2023). Triglycerides. Available at: https://my.clevelandclinic.org/health/articles/11117-triglycerides

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