Khanat Kruthkul., M.D.
Cardiovascular & Metabolic Center Ramathibodi Hospital
Faculty of Medicine Ramathibodi Hospital Mahidol University
สรุปเนื้อหางานประชุมวิชาการประจำปี 2561 จัดโดย สมาคมโรคหลอดเลือดแดงแห่งประเทศไทย วันที่ 26 มกราคม 2561
Abstract
Cardiovascular disease (CVD) ranks among the most common health-related and economic issues worldwide. Dietary factors are important contributors to cardiovascular risk, either directly, or through their effects on other cardiovascular risk factors including hypertension, dyslipidemia and diabetes mellitus, metabolic syndrome and lifestyle risk factors such as unhealthy diet, smoking and physical inactivity. Dietary factors are also important contributors to cardiovascular risk, either directly, or through their effects on other risk factors including hypertension, dyslipidemia and diabetes mellitus.
The term “Nutraceutical” was coined by combining the terms “Nutrition” and “Pharmaceutical”. A nutraceutical is defined as a “food, or parts of a food, that provide medical or health benefits, including the prevention and treatment of disease”. By both researches have been shown to the role of nutraceutical in the preventing of cardiovascular disease. The first research published on 2016. It was found to reduced serum total cholesterol and LDLcholesterol levels. No change in serum HDL-cholesterol levels, reduced serum total cholesterol, LDL-cholesterol, and HDLcholesterol levels, reduced serum total cholesterol levels and LDL-cholesterol levels and an additive effect was observed when berberine was taken in combination with statins. Coenzyme Q10 observed in human monocyte-derived macrophages. who were either given placebo or CoQ10 supplements twice a day for 1 week and it was found to reduced plasma levels of pro-inflammatory markers, and no changes in plasma levels of anti-inflammatory markers, enhanced endothelial function, but no changes in blood pressure and serum CRP levels but CoQ10 and garlic supplementation reduced serum CRP levels. Curcumin randomised double-blind trial involving 240 individuals with type 2 diabetes reported a decrease in CVD risk with 6 months of curcumin dietary supplementation, exemplified through a lower pulse wave velocity and improved metabolic profile. Furthermore, the use of curcumin for 8 weeks improved flow-mediated dilatation in 32 postmenopausal women and it was found to reduced arterial stiffness and improved endothelial function. Hydroxytyrosol randomly assigned 90 participants into three treatment groups, patient’s regular diet, Mediterranean diet and virgin olive oil (328 mg/kg polyphenols) or Mediterranean diet and washed virgin olive oil (55 mg/kg polyphenols) for 3 months and it was found to reduced risk of CVD-event, correlation between phenolic content of olive oils and increased serum HDL levels, reduced serum oxLDL levels, reduced expression of inflammatory biomarkers. The second research published on 2017.
Current medical treatments for the management of diabetes in some especially high risk patients are insufficient and current evidence suggests that the application of nutraceuticals may have the potential to increase the effectiveness of therapy (as well as to reduce the residual risk). Many of the nutraceuticals investigated for the prevention and treatment of Cardiovascular disease are well tolerated in patients. However, there is often insufficient data available with respect to long-term safety and effectiveness against clinical outcomes.
Introduction
Cardiovascular disease (CVD) is the most common cause of mortality in high income countries. Today, it has the same meaning for health care as the epidemics of past centuries had for medicine in earlier times: 50% of the population in such countries dies of cardiovascular disease. The number of cardiovascular disease is also increasing in the developing countries together with economic growth. By 2015 one in three deaths will globally be due to cardiovascular diseases. Coronary heart disease is a chronic disease that starts in childhood, even if the symptoms firstly occur in the middle age. The risks of coronary heart disease are well-known including lipid disorders, especially high serum LDL-cholesterol concentration, high blood pressure, smoking, obesity, diabetes, male gender and physical inactivity. Obesity is an independent risk factor for cardiovascular disease and is also closely connected with several other risk factors. This review focuses on the connection between overweight or obesity and cardiovascular disease which is commonly related to atherosclerosis.
Atherosclerosis (American Heart Association, 2017: Online) is a big word for a big problem: fat deposits that can clog arteries. These buildups are called plaque which is made of cholesterol, fatty substances, cellular waste products, calcium and fibrin (a clotting material in the blood). It sometimes deposits in arteries that can be compared to a plumbing problem; sludge forming inside the pipe. However, it is not a perfect comparison because of the fact that buildups do not just form on artery walls but inside them. As plaque builds up, an artery wall gets thicker resulting in narrowing the opening as well as reducing blood flow and oxygen supply to cells. The type of artery affected and where the plaque develops varies amongst individuals. Plaque may partially or totally block blood flow through a large or medium-sized artery in the heart, brain, pelvis, legs, arms or kidneys. Once it happens, various diseases are the consequences. For example, coronary heart disease refers to the plaque in arteries in or leading to the heart, angina is a chest pain from reduced artery blood flow to cardiac muscle, carotid artery disease is the plaque in neck arteries that supply blood to the brain, peripheral artery disease (PAD) is the plaque in arteries of the extremities, especially the legs and chronic kidney disease. Those aforementioned abnormalities can cause a heart attack or stroke.
Baker Heart and Diabetes Institute, 2013 There are reported that heart attack occurs when a blood clot blocks the artery that supplies blood to the cardiac muscle itself. Such occurrence leads to angina; a temporary chest pain or discomfort, is often a warning sign of an impending heart attack. The common symptoms of a heart attack are chest pain which may feel like tightness, pressure, heaviness, fullness or squeezing. It can vary from mild to severe and suddenly occur or develop over minutes. Pain or discomfort in the neck and throat (causing a choking feeling), jaw, shoulders and back, left arm (causing a heavy and numbness) and into the wrist and hands.
A stroke occurs when blood flow to the brain is interrupted. There are two types of stroke categorized by the cause of it the rupture of blood vessel in the brain haemorrhagic stroke and the arterial blood clot blocks the flow to the brain ischaemic stroke. The common symptoms of a stroke are weakness, numbness or paralysis of the face or one or both arms or legs. Trouble in speaking or understanding dizziness, loss of balance or unexplained fall. Blurred or loss of vision in one or both eyes. Sudden and severe headache, different to any usual patterns of headache difficulty in swallowing confused and unconsciousness
Other Types of Cardiovascular Disease
Heart failure it does not mean that the heart stops beating. Heart failure, sometimes called congestive heart failure, means the heart is not able to pump the blood as well as it should. The heart keeps working, but the body’s need for blood and oxygen is not being met. Heart failure can get worse if it is not treated. It is very important to follow the doctor’s orders in such case.
American Heart Association, 2017 There are reported that arrhythmia is an abnormal rhythm of the heart. There are various types of arrhythmias. The heart can beat too slowly, too fast or irregularly. Bradycardia is when the heart rate is less than 60 beats per minute. On the other hand, tachycardia is when the heart rate is more than 100 beats per minute. An arrhythmia can affect how well the heart works. The heart may not be able to pump enough blood to meet the body’s needs.
Stenosis is when heart valves do not open enough to allow the blood to flow through as it should. Regurgitation is when the heart valves do not close properly and allow blood to leak through. Prolapse is when the valve leaflets bulge or prolapse back into the upper chamber, it is called prolapse.
Nutraceutical
The term “nutraceuticals” was introduced by Stephen DeFelice, founder and chairman of the Foundation for Innovation in Medicine, in 1989. A nutraceutical is defined as a “food, or parts of a food, that provide medical or health benefits, including the prevention and treatment of disease” (7). The definition encompasses medicinal products made from natural ingredients. Several classes of nutraceuticals have been proposed to have potential benefits in the treatment of CVD and the ones with the strongest evidence are briefly summarized below.
Definitions of Nutraceutical
- A nutraceutical is any substance considered as a food, which provides health benefits including the prevention of disease or promotion of health.
- It is any non-toxic food component that has scientifically proven health benefits, including disease treatment or prevention.
- The functional component of the food must be standardized in the nutraceutical product and produced under good manufacturing practices.
Concept of Nutraceutical
Nutraceutical therapies
Definitions of Nutraceutical is any substance considered as a food, which provides health benefits including the prevention of disease or promotion of health. It is any non-toxic food component that has scientifically proven health benefits, including disease treatment or prevention. The functional component of the food must be standardized in the nutraceutical product and produced under good manufacturing practices.
Figure 1: The expression of pro-inflammatory genes, including ICAM-1 and MCP-1, is triggered by the build-up of modified LDL in the neighbouring endothelial cells during the development of the initial lesion. Circulating monocytes are then recruited to the modified LDL accumulation and migrate into the intima and differentiate into macrophages.
Figure 2: Once in the walls of the artery, the macrophages are able to take up the modified LDL and become lipid-laden foam cells, which can accumulate and form a fatty streak
Figure 3: During complex lesion formation, foam cell lysis by apoptosis and necrosis leads to the formation of a necrotic core, and together with defective efferocytosis, leads to the amplification of the in flammatory response. SMCs begin to migrate from the media to the intima and the ECM produced by them forms fibrous cap and stabilises the plaque. SMCs also transform to foam cells. During later stages of the complex lesion the plaque can become unstable owing to the inflammatory response, resulting in an inhibition of ECM formation, particularly collagen production by SMCs. The remaining ECM can then start to be degraded by pro teases released by macrophages, resulting in an unstable lesion
that can rupture and lead to thrombosis. These events can cause a myocardial infarction or stroke, depending on the location of plaque formation
Figure 4: The stages of atherosclerosis development at which different nutraceuticals exert their potential beneficial effects
Formation of atherosclerotic plaque
There are several major steps involved in the development of atherosclerosis including LDL oxidation, pro-inflammatory gene expression, monocyte migration, foam cell formation, and plaque stability.
Those aforementioned nutraceuticals have been shown to potentially exert anti-inflammatory effects making them promising compounds to explore for novel anti-atherogenic therapies. Moreover, there several other less-studied nutraceuticals such as Berberine, Carnosine, Coenzyme Q10, Curcumin, Lycopene, and Resveratrol. Although nutraceuticals are showing some promise, large, robust clinical trials are required to determine their full effectiveness in attenuating/regressing atherosclerosis disease progression.
Hypertension
Hypertension is an important modifiable risk factor for CVD. It has been shown that lowering blood pressure reduces CV risk by 20 – 25% for myocardial infarction, 35 – 40% for stroke and about 50% for heart failure. The evidence relating to antihypertensive effects of selected nutraceutical is outlined below.
Sterols / Stanosis one recent study, which aimed to analyze the effect of plant stanol esters on arterial stiffness and endothelial function in adults also found no effect on measured blood pressure.
Polyphenols grape seed extract significantly reduced systolic blood pressure by 5.6% and diastolic blood pressure by 4.7% after 6 weeks of supplementation in subject with mildly elevated blood pressure.
Cocoa flavanols are the most studied polyphenols in the clinical setting. Very recent clinical studies also confirm that cocoa flavanols exert a beneficial impact on blood pressure in patients with type 2 diabetes and hypertension and in elderly subjects.
A recent meta–analysis on the effects of green tea intake on risk of CVD indicated that consumption of green tea is associated with reduced risk of myocardial infarction and stroke. The nutraceutical product, Armolipid Plus (containing red yeast rice, policosanol, berberine, folic acid, astaxanthin and coenzyme Q10) was found to be safe, well tolerated and effective in reducing mean 24-h systolic and 24-h pulse pressure in hypertensive and hypercholesterolemic subjects at low cardiovascular risk.
Spirulina no effect of Spirulina upon blood pressure was observed after consumption of 1 g Spirulina per day for 12 weeks in a Greek population. Administration of 2 g Hawaiian Spirulina for 3 months was associated with improved blood pressure and endothelial function in patients with hypertension. However, evidence relating to cardiovascular outcomes is lacking and further well-designed trials are required to clarify its effects.
Summary of potential cardiovascular benefits of nutraceuticals in human studies
Diabetes Mellitus
Diabetes mellitus is a well-established risk factor for CVD. Diabetes mellitus type 2 is associated with high risk for developing cardiovascular complications. Moreover, patients with diabetes and hypertension have about twice the risk of cardiovascular events as non-diabetic patients with hypertension. It has been estimated that the global prevalence of diabetes mellitus will rise to 552 million by 2030. Observational studies indicated that diet is one of the factors, which might prevent diabetes and its complications. One study demonstrated that a diet characterized by a higher intake of total polyphenols was associated with a better cardiovascular risk factors profile and a lower grade of subclinical inflammation in population with diabetes mellitus type 2
Polyphenols red wine consumption is associated with a 30% risk reduction fortype 2 diabetes. Consumption of grape seed polyphenols and red wine grape pomace flour has been associated with significant reductions in blood glucose.
Chocolate or cocoa reduced fasting insulin concentrations and improved insulin resistance. Consumption of chocolate high in polyphenols was not associated with differences in fasting insulin in patients with diabetes mellitus type 2 and hypertension.
Green tea consumption was associated with significantly reduced fasting glucose and hemoglobin A1c. Recent meta-analysis found that tea could alleviate the decrease of fasting blood insulin and reduced waist circumference only when the intervention was extended for longer than 8 weeks. However, it is still unclear whether green tea has anti-diabetic effects.
Polyphenols might influence glucose homeostasis by several mechanisms, by inhibiting carbohydrate digestion and glucose absorption in the intestine, protecting pancreatic β-cells, reducing glucose release from liver and activating insulin receptors and glucose uptake in insulin-sensitive tissues.
Spirulina is supplementation of 2 g/day for 2 months resulted in reduced fasting blood glucose, postprandial blood glucose levels and HbA1c. Conversely oral supplementation of Spirulina in a separate trial (4.5 g/day, for 6 weeks) did not result in changes in the markers of glucose metabolism. Further trials are required to clarify the clinical value of Spirulinan supplementation in treatment of diabetes.
Conclusion
There is growing evidence that nutraceuticals are able to exert cardiovascular protective effects and reduce an individual’s risk of suffering a cardiovascular diseaserelated event such as a stroke. Further studies are required to fully evaluate the effectiveness of some of the nutraceuticals mentioned in this review. Such advances in our understanding of nutraceutical actions will lead to the identification of novel treatment and prevention strategies in order to reduce the global prevalence of cardiovascular disease.
Hypertension and diabetes are major modifiable risk factors for cardiovascular disease. Current medical treatments for the management of diabetes in some especially high risk patients are insufficient and current evidence suggests that the application of nutraceuticals may have the potential to increase the effectiveness of therapy (as well as to reduce the residual risk). Many of the nutraceuticals investigated for the prevention and treatment of cardiovascular disease are well tolerated in patients. However, there is often insufficient data available with respect to long-term safety and effectiveness against clinical outcomes such as myocardial infarction and mortality. Further clinical research should be conducted to identify nutraceuticals with the best clinical and cost-effectiveness in the prevention and treatment of cardiovascular disease.
References
- Baker.edu.au. (2018). What is cardiovascular disease?. [online] Available at: https://www.baker.edu.au/health-hub/fact-sheets/cardiovascular-disease [Accessed 18 Jul. 2018].
- Chhetri, M. (2018). Nutraceuticals. [online] Slideshare.net. Available at: https://www.slideshare.net/ManjuChhetri/nutraceuticals-71153808 [Accessed 18 Jul. 2018].
- Moss, J. and Ramji, D. (2016). Nutraceutical therapies for atherosclerosis. NatureReviews Cardiology, [online] 13(9), pp.513 – 532. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228762/ [Accessed 18 Jul. 2018].
- Sosnowska, B., Penson, P. and Banach, M. (2017). The role of nutraceuticals in the prevention of cardiovas cular disease. Cardiovascular Diagnosis and Therapy, [online] 67(1), pp.S21-S31. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418215/ [Accessed 17 Jul. 2018].
- www.heart.org. (2018). What is Cardiovascular Disease?. [online] Available at: http://www.heart.org/en/health-topics/consumer-healthcare/what-is-cardiovascular-disease [Accessed 18 Jul. 2018].
