This article will help you:
- Understand the importance of advanced lipoprotein testing, beyond the standard cholesterol test.
- Explore the relevance of assessing metabolic risk factors when assessing your patients' cardiovascular health.
- Understand the relevance of also including inflammatory markers, as well as other relevant testing to consider.
Around 7.6 million people are living with cardiovascular disease (CVD) in the UK, and it is estimated that more than half of us will get a heart or circulatory condition in our lifetime. Heart and circulatory diseases cause around a quarter of all deaths in the UK, estimated to be one death every three minutes (bhf.org.uk).
The most common type of CVD is coronary heart disease (CHD), which occurs when coronary arteries become narrowed by a build-up of atheroma. It is estimated that one in eight men and one in 14 women die from CHD.
Strongly associated risk factors for CVD are clustered in Metabolic Syndrome (MetS), namely abdominal obesity, dyslipidaemia, hyperglycaemia, and hypertension. MetS greatly increases the risk of developing diabetes, heart disease and stroke. With more than one-third of the world’s adult population now classified as overweight or obese and approximately 25% meeting the criteria for the MetS, functional medicine practitioners and nutritional therapists are in a unique and valuable position to educate and support their patients with this dietary and lifestyle-modifiable condition.
The Relevance of Functional Testing in Cardiovascular Health
In-depth testing is warranted, as this moves beyond a standard cholesterol test (also known as a lipid profile) that measures total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TGL) levels.
Functional testing can include a closer evaluation of the LDL subspecies, metabolic drivers, and inflammatory markers. Doctor’s Data Cardiometabolic Serum will be discussed below.
Evaluation of thyroid health is important as both thyroid hormone excess and deficiency can induce or exacerbate CV disorders. Reductions in thyroid levels can trigger an elevation in cholesterol levels due to the crucial role thyroid hormones play in facilitating hepatic blood processing. Thyroid Complete Blood Test or a more comprehensive blood panel such as Wellness 360 Female or Wellness 360 Male all include TSH, free T4, free T3, anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies along with standard lipid markers and vitamin D. Deficiency of vitamin D is a well-established risk for CVD (Grandi et al, 2010) and hypertension (Wang et al, 2008). Liver markers included in the Wellness panels are also useful (Targher et al, 2015).
Gut microbiota dysbiosis also plays a crucial role in the development of various obesity-related metabolic abnormalities, among them type 2 diabetes (T2D) and CVD, along with intestinal permeability, due it its influence on systemic inflammation, both are important aspects to consider (Guiducci et al 2023). Doctor’s Data GI360 Complete offers a comprehensive assessment of GI health.
Testing can provide clinicians and patients with a breadth of actionable information to inform dietary and lifestyle interventions and provides an invaluable tracking tool. To better exploit the potential predictive capacity of blood biomarkers, be aware that tracking blood markers over time as trends can tell us more than stand-alone numbers, ratios can be powerful indicators of risk and biomarkers should be correlated with others to give broader insight.
The Cardiometabolic Serum from Doctor’s Data measures:
- Traditional cholesterol markers: Total cholesterol, LDL, HDL, TGls
- Advanced lipoprotein testing measuring size, distribution, and number of the most highly atherogenic apolipoprotein B-containing lipoproteins, considered the real LDL culprits: oxidised LDL, small dense LDL and lipoprotein (a) which have been shown to have a greater predictive power than LDL alone. These are irrespective of TG levels which is important as calculated LDL and VLDL cholesterol values may be markedly underestimated with plasma TG are high.
- Metabolic markers: fasting glucose, insulin and 1,5-anhydroglucitol (Glycomark®) – a marker of short-term glycaemic control.
- Primary adipokines associated with insulin sensitivity and hepatic fatty acid metabolism: leptin and adiponectin.
- Inflammatory markers: Homocysteine, lipoprotein-associated phospholipase-A2 (PLAC®) and eCRP. CVD is an inflammatory condition.
- Kidney function: Cystatin C to assess glomerular filtration.
- Key ratios are also presented.
NB this test requires a single blood collection after an overnight fast and that the sample be centrifuged.
A closer look at the key lipid markers:
Triglycerides (TGl) and cholesterol are water-soluble molecules that must be solubilised into plasma lipoproteins so that they can be transported through aqueous plasma from sites of absorption, synthesis or storage to tissues that require them for energy production and other cell functions. Lipoproteins can be categorised by density:
Very low-density lipoproteins (VLDL) are made continuously by the liver to the bloodstream and carry different types of fats, especially TGls, to the cells. High VLDLs are associated with atherosclerosis (Packard, 2023)
Low-density lipoproteins (LDL) the major cholesterol-carrying lipoprotein which takes TGls and cholesterol from the liver to the periphery and cells within the artery wall, with a role in plaque formation.
High-density lipoproteins (HDL) have a role in transporting cholesterol from peripheral tissues and arterial walls to the liver for excretion.
Oxidised LDL
Oxidized low-density lipoprotein (OxLDL) is considered a strong and independent risk factor for cardiovascular disease with roles in both the initiation and progression of atherogenesis (Holovet, et al. 2001). The uptake of OxLDL by scavenger receptors leads to the accumulation of cholesterol within the foam cells of atherosclerotic lesions. OxLDL has many stimulatory effects on vascular cells and accumulates in atherosclerotic lesions over a long duration, leading to advanced lesions (Nishi et al, 2002). OxLDL is associated with acute MI, angina, MetS (Holvoet et al, 2008), and hypothyroidism (Duntas et al, 2002). Dietary and lifestyle risk factors include consumption of trans-fatty acids and insufficient antioxidants, smoking, toxicant exposures, and oxidative stress.
Lipoprotein(a)
Lipoprotein (a) (Lp(a) is a complex of a cholesterol-rich LDL particle and a large protein apo(a), which is associated with increased risks of atherosclerosis, thrombosis, and aortic valve calcification. It is understood that there is a genetic predisposition for increased levels of Lp(a) and is less influenced by diet and lifestyle (Nordestgaard & Langsted, 2016) (Reyes-Soffer et al, 2021)
Small Dense LDL
Smaller, denser LDL (sdLDL) is particularly problematic as is more easily oxidised, has a higher affinity for vessel walls and remains in circulation longer because it is less likely to be cleared by the liver (Jin et al, 2022). This makes it more atherogenic than larger LDL particles. Increased sdLDL levels are found in patients with MetS (Fan et al, 2019) (Rizzo et al, 2007) and are often seen with increased levels of TG and reduced HDL-C (Rizzo et al, 2006).
Apo B serves as the principal apolipoprotein in chylomicrons, VLDL, Lp(a), IDL, and LDL particles, those carried to the periphery, and thus a direct indication of the particle number of those atherogenic non-HDL lipoproteins, as it facilitates the organised assembly of these lipoprotein complexes. It is involved in the structural orchestration of these particles, essential for their formation, as well as signalling functions. The apo B acts as a ligand for LDL receptors, thus mediating cellular uptake and intracellular lipid delivery.
Apo A1 reflects the presence of anti-atherogenic HDL particles and promotes cholesterol efflux from the artery wall to the liver for excretion.
Looking at the apo B to apo A1 ratio offers valuable functional insights into the balance of cholesterol and provides an estimation of net reverse cholesterol transport which is vital to understanding the dynamics of cholesterol-related processes and their impact on cardiovascular health (Walldius et al, 2001)
The Importance of Arterial Inflammation Markers
PLAC® - Lipoprotein-associated phospholipase A2 (LP-PLA2) is an enzyme associated with lipoproteins, particularly LDL and HDL. LP-PLA2 plays a role in the inflammatory
processes within blood vessels and elevations may indicate an increased risk of atherosclerosis with vascular inflammation (Ferguson et al, 2012). Activation of LP-PLA2 is involved in the modification of LDL particles, making them more prone to accumulating in the arterial walls and generating pro-inflammatory and pro-atherogenic substances (Gonçalves et al, 2012).
Homocysteine
Elevated levels of homocysteine indicate significant disruption of essential methionine metabolism that can impair all essential methylation reactions, and impair the transsulfuration pathway with potentially diminished redox potential and increased oxidative stress. Methionine metabolism can be disrupted by genetic and epigenetic factors; the latter include deficiencies of vitamins B-6, B-12 and folate (and other methyl donors methionine, betaine (TMG) and choline). Homocysteine is an independent CVD risk factor modifiable by diet and lifestyle (Ganguly & Alam 2015).
hsCRP
Elevated level of hsCRP is a well-established indicator of arterial inflammation, myocardial infarction, stroke and peripheral arterial disease (Bassuk et al. 2004).
Metabolic Risk Markers
Glycomark®
In addition to insulin and glucose, Glycomark® (1-5 Anhydroglucitol) provides an estimate of postprandial glucose over two weeks. When blood glucose is well-controlled, glucose and 1,5-AG circulate in the bloodstream. The molecules are filtered by the kidneys and reabsorbed by the body. When glucose exceeds the renal threshold) reabsorption of 1,5-AG is blocked and excreted in the urine resulting in lower serum 1,5-AG levels. A low GlycoMark® level therefore helps reveal frequent high glycaemic episodes, even when haemoglobin A1C (HbA1c) levels are normal. Glycomark® can also help monitor the effectiveness of dietary, lifestyle and supplementation interventions to support glucose control (Dungan et al, 2006) (Dworacka et al, 2002) and (Bonora et al, 2006).
Adipocytokines
Leptin inhibits appetite, stimulates fatty acid oxidation, facilitates glucose homeostasis and modulates body fat. Increased abdominal adiposity increases serum leptin often resulting in leptin resistance (selective). This leads to a loss of satiety signalling, but stimulates sympathetic nerve activity (CNS, adrenal, kidneys, heart) and increases vascular inflammation, oxidative stress, IR, and hypertension, and is associated with an atherogenic lipid/lipoprotein profile (Wallace et al. 2001)
Adiponectin, on the other hand, is anti-inflammatory & most abundant adipocytokine in blood. It helps modulate insulin resistance, energy balance, hepatic and muscle fatty acid oxidation, hepatic TG secretion and supports the proper function of endothelial cells. Serum adiponectin levels decrease with increasing adiposity resulting in pro-inflammatory cytokines and oxidative stress. Low serum adiponectin is associated with obesity, T2D, hypertension, CAD and left ventricular hypertrophy (Chen et al, 2012) (Kumada et al, 2003).
The Leptin: Adiponectin ratio can be even more sensitive than measuring leptin or adiponectin alone and has been associated with increased incidence of insulin resistance and CVD (Frühbeck et al, 2018) and is considered an independent predictor of arterial intermedial thickness (Norata et al, 2007).
Renal Markers
Cystatin C, along with creatine, can be used to assess glomerular filtration rate to help assess kidney function (Murty et al, 2013), which may be compromised with inefficient circulation and vice versa.
When to consider the CardioMetabolic Serum:
- Family or personal history of CVD
- Excess abdominal fat
- Obesity
- Insulin resistance
- Fatty liver disease
The information gleaned from in-depth testing provides actionable information to dictate key dietary, lifestyle, and supplemental interventions. Testing can be highly motivational for patients as results can highlight areas of concern and improvements can be tracked over time. Retesting is usually recommended after around 6 months.
Buy the CardioMetabolic Serum now!
Refs
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