February (RedFeb) is Heart Research Month – and this is a topic that I am really excited about. I believe that our understanding of heart disease is far from complete. Once we have a deeper insight into how exactly it develops we will have a whole new toolkit for prevention and early diagnosis. So, let’s dive in…
‘Traditional’ risk factors for heart disease are hypertension, high cholesterol, diabetes and smoking. But, an increasing proportion of people suffering from heart attacks do not have any of these risk factors. What is even more worrying is that these patients have much worse outcomes after their heart attacks – they are 50% more likely to die in the first 30 days after their heart attack.
A team based at the University of Sydney is now looking at factors that could be contributing to heart attacks in patients who do not have any of the well-known ‘traditional’ risk factors. They are looking at the possible involvement of inflammatory pathways, environmental exposure, autoimmune disease and genetics. They are also trying to identify biochemical markers that could alert us to an increased risk, such as C-reactive protein, lipoprotein (a) and some gene variations.
In my practice, I pay close attention to the ‘traditional risk factors’ but I also like to look beyond. Here are some of the biochemical markers, genes and other factors that I pay close attention to:
Insulin
Insulin resistance is marked by the declining ability of tissues to respond to insulin. Cells struggle to take up glucose from the bloodstream ultimately resulting in damage to the lining of the blood vessels. In an attempt to solve this problem, the body produces even more insulin. Eventually, the cells take up glucose but only after being exposed to very high levels of insulin. This in itself has a pro-inflammatory effect.
There are 2 main ways of looking at Insulin. One is fasting Insulin, which gives us a good idea of baseline insulin sensitivity. It is a quick and easy blood test to do. Another way is to look at what happens to insulin and glucose levels following ingestion of a very sweet drink – a ‘glucose challenge’. This is a more challenging test but it gives us very good information about how the body might respond in real-life situations.
Insulin resistance is one of the earliest markers of cardiometabolic disease and can precede the diagnosis of diabetes and cardiovascular disease by a number of years. Best of all, insulin resistance can be reversed through lifestyle, diet, exercise and herbal supplements that improve insulin sensitivity.
High Sensitivity CRP (hs-CRP)
CRP is a protein produced by the liver in response to inflammation. Elevated levels of hs-CRP are associated with inflammatory processes affecting the blood vessels and increased risk of atherosclerosis. It is particularly interesting that increases in hs-CRP have been noted in patients who had heart attacks and strokes but had no other traditional risk factors.
Homocysteine
Homocysteine is an amino acid that is a risk factor for atherosclerosis, cardiovascular disease and stroke. Homocysteine is produced by the body as a result of normal metabolic processes and is usually rapidly broken down. However, deficiencies in Vitamins B6, B12 and folate and certain genetic variants can slow down homocysteine metabolism. Elevated homocysteine levels can cause damage to the walls of arteries, promoting the formation of plaques and blood clots.
We can use blood tests to check for levels of homocysteine and vitamins that are essential for homocysteine metabolism. Furthermore, genetic testing can identify gene variants that slow down biochemical reactions required to clear homocysteine. Targeted lifestyle, nutritional and nutraceutical interventions can help overcome these metabolic bottlenecks.
LDL particle size
Low-density lipoprotein (LDL) is often referred to as ‘bad cholesterol’ because high LDL levels have been linked to an increased risk of cardiovascular disease. LDL particles come in a variety of sizes – you can imagine them as balloons. Some of them are large and light, able to bounce off the walls of arteries. The others are small and heavy and are more likely to penetrate the walls of blood vessels and initiate the process of plaque formation.
The number of ‘balloons’ particles seems to matter too – the higher the number of particles, the greater the risk of plaque formation and consequently cardiovascular disease and stroke.
We can measure both the size and number of LDL particles and this can help us think about potential future risks of cardiovascular disease. A person who has a very high number of small particles would be at a greater risk. Again, there are many interventions that can shift both LDL particle size and number.
Coronary Calcium Score
A coronary calcium score is a non-invasive test that uses CT imaging to measure the amount of calcium in the coronary arteries. The score is calculated based on the amount of calcium detected in the arteries – higher scores indicate a greater amount of plaque and a higher risk of cardiovascular disease.
This test is usually recommended for people who are not symptomatic but are considered at a higher risk due to their age, family history, genetics or have some of the traditional cardiovascular risk factors. The results can guide decisions about lifestyle interventions, medications and further testing.
Genetics
Although there is no single gene that determines the risk of cardiovascular disease, we know of a number of gene variants that can contribute to the risk profile. Some of them include:
- Lipoprotein-a (LPA)
- Low-density lipoprotein receptor (LDL-R)
- Apolipoprotein E (APOE)
- Endothelial nitric oxide synthase (eNOS)
Some of these genes are linked to the body’s ability to clear cholesterol out of the bloodstream while others are important for the health of blood vessel walls and the maintenance of healthy blood pressure. It is important to remember that, in this case, genetics does not determine the outcome – even when genetics is not on your side there is a lot that we can do to prevent cardiovascular disease.
Being female
The way in which the heart and circulatory system age in women is quite different from what happens in men. Hormone fluctuations have a significant effect, menopause and dropping estrogen levels affect the structure of coronary arteries and heart attacks in women often do not present with classic symptoms we see in men. In fact, women are 50% more likely to be misdiagnosed following a heart attack.
Migraines, hypertension in pregnancy, early menopause and inflammatory and rheumatological conditions are additional risk factors for heart disease in women. There are many things we can do to make sure that women get assessments and treatments better suited to them. ‘A Woman’s Heart’ by Dr Angela Maas is a fascinating book that deep dives into this topic.
