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Cardiovascular disease

The term “cardiovascular disease” is an umbrella term used to describe a wide range of diseases caused by the narrowing of blood vessels, and the consequences caused by it.

The most common cardiovascular disease (and most deadly) is coronary artery disease (CAD) which is also an umbrella term for a variety of diseases such as angina (chest pain), myocardial infarction (heart attack), etc.

Coronary artery disease is the number one killer in the world, accounting for more than 17.6 million deaths in 2016 alone!

It is also predicted to take the lives of 23.6 million people by the year 2030.

The numbers are just crazy! Coronary artery disease is becoming an epidemic and the death toll is only increasing every year.

Cardiovascular disease (CVD) pathogenesis

The pathophysiology of cardiovascular disease is quite complex and multifactorial; it’s basically the combination of nature and nurture. Let’s briefly discuss the risk factors of developing ischemic heart disease (aka coronary artery disease).

Unmodifiable risk factors:


As we age, our blood vessels become weaker and narrower, which increase the risk of coronary artery disease.


Men are at greater risk of heart disease compared to women. This is because women before menopause are better at regulating the metabolism of lipids due to high levels of estrogen.

Genetic predisposition (the nature part):

Having a family history of heart disease will increase your risk of coronary artery disease; this is especially true when a first-degree relative is diagnosed with CAD at an early age.

The exact pathophysiology behind this isn’t clearly understood. However, theories suggest that some genes predispose patients to higher levels of circulating cholesterol, higher levels of inflammation, and a less efficient hepatic regulation of lipids.

All of these factors will contribute to developing coronary artery disease.

Modifiable risk factors (the nurture part):


Cigarettes contain substances (e.g. nicotine, carbon monoxide) that work as vasoconstrictors (narrow blood vessels). This property will increase the risk of atheromatous plaques formation.

High blood pressure

Chronic hypertension will harden blood vessels rendering them unable to adapt to different physiological situations further damaging the vasculature.


Similar to blood hypertension, hyperglycemia (high blood sugar) will damage the vasculature making it more susceptible to atherosclerosis.


High blood cholesterol, high LDL, and low HDL have all been documented as risk factors of heart disease.


This isn’t particularly a unique risk factor; however, it will worsen other risk factors.


being in a constant state of stress means having high levels of stress hormone circulating in your blood; these hormones will damage blood vessels.

Now that we’re familiar with risk factors, let’s see how a heart attack happens.

As I mentioned earlier, the coronary arteries are a group of blood vessels supplying the heart muscle with the necessary oxygen and nutrients to stay functional.

A narrowing in one or more of these vessels means less or no blood reaching a particular area of the heart; this will stop the heart from working, and it’s what we call a heart attack.

How do these vessels narrow down and get obstructed?

Well, it first starts when cholesterol levels circulating in the blood are high; cholesterol will then infiltrate under the innermost layer of the affected blood vessel (intima), macrophages (part of the immune system) will start to phagocytose (eat up) these cholesterol deposits.

As macrophages do this, they will release free radical creating a state of oxidative stress, as well as, inflammatory mediators which will only worsen the situation.

The combination of cholesterol deposits and the activity of macrophages will create an atheromatous plaque (a greasy substance that blocks the lumen of the blood vessel).

To summarize, high levels of cholesterol, the immune response, oxidative stress, and inflammation are the hallmarks of ischemic heart disease. This, in a nutshell, is how a heart attack happens.

Since this article is about the influence of polyphenols on circulatory disease, let’s take a look at how each risk factor is influenced.

Mechanisms of the underlying cardiovascular protection of polyphenols


Polyphenols can help with Circulatory Diseases


Multiple published studies have researched the effects of polyphenols on cardiovascular disease, and whether it can be helpful in the prevention and/or treatment of coronary artery disease and other heart diseases.

So far, all the evidence is in favor of polyphenols having an important role in reducing the risk of cardiovascular disease as well as helping in the management of patients who suffered from heart attacks.

Polyphenols and hypertension

As we mentioned earlier, blood hypertension is an important risk factor of coronary heart disease.

One of the major players in blood hypertension pathogenesis is oxidative stress; reactive oxygen species (ROS) released in blood circulation is a hallmark of hypertension, and as you may know, polyphenols are potent anti-oxidants.

In fact, polyphenols from red wine have been documented to reduce high blood pressure by stimulating the production of nitric oxide (NO), which is a strong vasodilator (enlarges blood vessels).

In a study published in 2016, flavonoids (a subclass of polyphenols) were found to significantly decrease diastolic blood pressure, reducing in return the risk of cardiovascular disease.

Polyphenols and Diabetes mellitus

Patients with type 2 diabetes have higher than normal blood sugar levels; this in return will induce the release of reactive oxygen species (ROS) that will damage blood vessels increasing the risk of coronary artery disease and stroke.

Additionally, hyperglycemia creates a state of constant inflammation; another risk factor of CVD.

Polyphenols stimulate the production of adiponectin and peroxisome proliferator-activated receptor-gamma (PPARγ). These two molecules will increase the cells’ sensitivity to insulin and act as anti-inflammatory mediators.

Moreover, the American journal of clinical nutrition published a study with the following results:

A short-term administration of polyphenols-rich dark chocolate was found to significantly increase insulin sensitivity as well as decrease blood pressure.

Polyphenols and Hyperlipidemia

Out of all the risk factors we cited above, hyperlipidemia is the most important one; it involves the induction and release of large amounts of reactive oxygen species.

The consumption of polyphenols found in black tea has been associated with a decrease in the surface area of the atherosclerosis plaque, a reduction in the number of lipids absorbed, and increased lipid-excretion in feces.

Polyphenols and obesity

Obesity creates a state of constant inflammation as well as increased insulin resistant and higher concentrations of reactive oxygen species in the bloodstream.

By decreasing the levels of leptin (a proinflammatory mediator) produced by adipose tissues (fat tissues), green tea polyphenols can be a potent food-source for reducing inflammation.


Polyphenols and atherosclerosis pathology

Endothelial dysfunction

The endothelium is the innermost layer of cells inside blood vessels. Increased oxidative stress has been firmly associated with endothelial dysfunction which is one of the hallmarks of atherosclerosis/cardiovascular disease.

Polyphenols have been shown to provide the protection of blood vessels from reactive oxygen species by increasing the production of vasodilators (e.g. nitric oxide).

Oxidized LDL (bad cholesterol):

The oxidation of LDL plays a major role in the pathology of atherosclerosis, increasing the risk of ischemic heart disease, ischemic stroke, and peripheral artery disease.

Studies have shown that phenolic substances found in red wine reduce the oxidation of LDL.

The inflammatory process of the immune system

As we mentioned before, the immune system and in particularly macrophages are a key component of the pathogenesis of atherosclerosis; this is mediated by the release of proinflammatory chemokines.

In a study published by the British journal of nutrition, short-term administration of polyphenols has been shown to reduce the release of these chemokines, as a result inflammation is downregulated, which will eventually reduce the risk of CVD.


Coronary artery disease and ischemic stroke are the number one killer in the world with high rates of mortality and morbidity.

For this reason, researchers are redirecting their radars towards natural products that can be used in the prevention and/or treatment of cardiovascular disease; polyphenols are a strong candidate!

Multiple studies support the positive effect that polyphenols have on managing CVD as well as the significant effect of reducing risk factors, thus playing a preventive role as well.

However, further investigation needs to be done to get a better understanding of how to use this information in a practical way.

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