Atherosclerosis


Joel Kahn, MD

Atherosclerosis is a common condition that develops when plaque builds up inside arteries throughout the body, literally head to toe.  Diseases linked to atherosclerosis, such as stroke and heart attack, are the leading cause of death in the United States and the Western world. Even more shocking is that about half of Americans between ages 45 and 84 have atherosclerosis and don’t know that it is present and threatening their health.

Atherosclerosis develops slowly as cholesterol, calcium, fat, blood cells and other substances deposit or concentrate in the wall of arteries to create plaque. When the plaque builds up, it causes arteries to narrow. This reduces the supply of oxygen-rich blood to tissues of vital organs in the body and may suddenly occlude arteries leading to medical emergencies or death.

I was taught in medical school nearly 40 years ago that diseases of atherosclerosis like coronary artery disease (CAD)—the blockages that can choke off blood flow to the heart—progresses from minor “streaks” in youth, to visible plaques in young adulthood, and on to complicated plaques and major problems later in life. During my training, the direction of plaque was always one of progressive disease and never the possibility of reversing atherosclerosis. 

Actually, for decades, it has been known that just as arteries can worsen with time, they can also improve resulting in less plaque, less obstruction, fewer or no symptoms, and improved quality of life. Techniques to halt and reverse atherosclerosis should be the number one priority of medical practitioners.

How to Measure Atherosclerosis and Reversal

One way to assess the possibility of reversing atherosclerosis is to depend on traditional clinical assessments like relief of angina pectoris, exertional shortness of breath, nitroglycerin use, and overall well-being. After major lifestyle changes discussed below, patients may begin to feel better within weeks, providing indirect confirmation of improved blood flow and lesser degrees of obstruction. It would seem obvious, however, that directly examining the health of the approximate 50,000 miles of arteries in the body would provide direct information regarding progression or regression of vascular atherosclerosis and overall aging. As Thomas Sydenham, MD, said in the 1600s in England, “a man is as old as his arteries.” This is, of course, true for women too. Unless you can accurately identify and measure atherosclerosis in arteries, direct assessments of disease burden are not possible and demonstrating disease reversal is simply a hypothesis.

There are several widely available methods of assessing the burden of atherosclerosis in arteries using precise measurements to determine “arterial age.”

Coronary artery calcium score (CACS). This non-invasive examination is performed without contrast or IV injection and utilizes a high-speed, multi-slice, CT scanner. The examination of the heart arteries takes under a minute, is painless, is not claustrophobic, and has a radiation exposure that is similar too, or less, than a mammogram. In many cities the CACS test costs $100 or less. The CACS result ranges from the ideal score of zero to over 1,000 and up. An online calculator (astrocharm.org) uses the CACS and several other clinical markers to predict the 10-year risk of heart attack and stroke that is the most accurate available. The CACS can be repeated if desired to evaluate the progression of the calcified component of atherosclerosis over time.

Carotid intimal-medial thickness (CIMT). This is an ultrasound examination of the carotid arteries. The images are analyzed with digital software and the thickness of the inner two layers of the carotids are measured in mm. A healthy measure is around 0.6 mm and increased CIMT is a marker of atherosclerosis and vascular aging. The test is painless and without risk. There are databases for normal CIMT by age and gender. The report includes an arterial age measurement. The CIMT can be repeated to track the reversal or progression of atherosclerosis over time.

Coronary CT Angiography. There are two drawbacks to the CACS. The reports cannot indicate the percentage of narrowing in arteries. The CACS also does not detect non-calcified plaque, often called soft plaque, that is found in almost all arteries that also have calcified plaque. There is a more advanced CT study of heart and carotid arteries that involves injecting dye that is known as a CT angiogram or CTA. When it is performed on the heart arteries, it is called a coronary CTA.  A CTA is not as simple as a CACS as it requires a low heart rate and the injection of iodine contrast agent. There is risk of allergy and kidney reaction to the contrast agent and the cost can be about $500-1500. A coronary CTA, however, does report the percentage narrowing of all arteries and can identify both non-calcified and calcified atherosclerotic lesions. Finally, a coronary CTA can be analyzed using artificial intelligence software providing the most quantitative measurements to follow atherosclerosis progression or regression over time, including the reversal of non-calcified plaque (www.cleerlyhealth.com).

Nutrition and Lifestyle Programs and Reversal of Atherosclerosis

There is a long history of using nutrition to reverse clinical or radiologic measurements of atherosclerosis. Lester Morrison, MD, practiced internal medicine in Los Angeles in the 1940s and 1950s and had many heart patients but few therapies. He designed a plan for his heart patients that omitted rich foods like cream, butter, full fat dairy, olives, nuts avocados, oils, glandular organs, and egg yolks. His results were published in a well-respected medical journal and showed a greater than 50% drop in deaths in the largely plant-based diet group lower in fat at 12 years compared with a standard diet group.1 

Nathan Pritikin was an aerospace engineer in Santa Barbara and heard of the nutrition work being done by Lester Morrison, MD. Pritikin visited Dr. Morrison in the early 1950s and learned that his cholesterol was over 300. Pritikin dug into the books and designed a plant-based regimen rich in beans, low in fat, and combined it with walking. He was able to lower his cholesterol by nearly 200 points at a time when there were no drug therapies and slowly his stress test returned to normal. He wrote a book, The Pritikin Diet, that became an international best seller, and published many clinical research papers. His legacy lives on at the Pritikin Longevity Center and Spa in Miami, Florida.2

The first report of using actual coronary artery imaging assessments to demonstrate the reversal of atherosclerosis was provided by Dean Ornish, MD, and colleagues in 1990. Dr. Ornish prescribed a plant-based diet without added fats to patients with proven heart blockages. He also recommended walking, social support, and stress management to help their hearts. He demonstrated that the patients who adhered to his “lifestyle program” felt better and showed reductions in the amount of narrowing in their arteries, using serial invasive coronary angiograms measured accurately by quantitative methods. Dr. Ornish followed his patients for longer periods of time and with further testing and showed even more improvements, avoidance of hospitalizations, and reduced costs.3

Since those first reports, the data that heart disease can be reversed by intensive lifestyle changes emphasizing a plant-based diet low in added fats has become so robust that the Ornish Lifestyle program was recognized by Medicare in 2010 for reimbursement as a therapy of CAD. The Pritikin Program also received the same Medicare designation for intensive therapy and reversal of heart disease with dietary therapy, based on large numbers of Pritikin patients who were followed on clinical and lab data outcomes.

A similar program at the Cleveland Clinic Foundation led by Dr. Caldwell Esselstyn monitoring patients with advanced heart disease who converted to totally plant-based diets without added oils identified the same types of clinical improvements with documents shrinking and reversal of heart blockages.4

New Nutrition Data on Reversal: The CORDIOPREV Study

The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV) is a single center, randomized clinical trial aimed at assessing the superiority of a Mediterranean diet in the secondary prevention of cardiovascular disease (CVD), as compared with a lower fat diet.5

The study population consisted of 1002 patients (average age, 60 years; 83% males) with established coronary heart disease; 58% had the metabolic syndrome with a body-mass index of 31 kg/m2, 54% had diabetes, and 68% were hypertensive. Lipid-lowering, antithrombotic, and anti-hypertensive drugs were used by most patients. They were randomly assigned in a 1:1 ratio to receive a Mediterranean, high-olive oil diet or a lower fat diet, with a follow-up of seven years.  Extra-virgin olive oil and healthy lower-fat food were provided to each subject assigned to the Mediterranean or lower-fat diet, respectively.

After 198 primary-outcome events, the study was stopped: 87 (17.3%) occurred in the Mediterranean diet group (high-olive oil) and 111 (22.2%) in the lower-fat group. The unadjusted hazard ratio was 0.75 or a 25% reduction in the high olive oil group. The Mediterranean diet was consistently superior to the low-fat diet in all multivariable adjusted models.

In a separate publication by the CORDIOPREV study group, the high-olive oil randomized group was compared to the lower-fat group in terms of progression or regression of carotid atherosclerosis at 1 year.6 The high-olive oil MED diet group had reduced carotid thickness at five years and at seven years, a sign of improved arterial health and structure. There was no similar improvement in the control arm. No change in IMT after five or seven years was observed for the low-fat diet group. Furthermore, reductions in carotid plaque height were observed in the Mediterranean diet group, while the low-fat group demonstrated no such change.  The investigators concluded that long-term consumption of a Mediterranean diet rich in extra virgin olive oil was associated with decreased atherosclerosis progression, as shown by reduced IMT-CC and carotid plaque height, compared to a low-fat diet.

Statin Medication and Plaque Reversal

While reversal of clogged heart arteries with statin cholesterol-lowering medication has been shown before,7 most of the studies with statins actually looked at clinical endpoints like heart attack and survival. A study looked at a database of 13,644 patients assessed for heart artery disease by a coronary calcium CT scan and followed for over 9 years.8 The group was also analyzed as to whether they were on a statin medication to lower their cholesterol. When the CACS was >100, treatment with a statin was associated with a lower risk of adverse outcomes. In fact, when the calcium score was over 100, only 12 patients needed to receive a statin to prevent one event like a heart attack, stroke, or death.

There was no proven benefit to using statin medication when the CACS was zero or even <100. Statin medications do not lower the CACS over time and may even increase the annual rate of rise in the CACS by promoting the conversion of non-calcified plaque to calcified regions of atherosclerosis, an outcome that may lower the risk for clinical events.

Plaque Reversal

Several nutraceuticals have been studied in human randomized trials where plaque reversal was the endpoint measured.

Aged Garlic. The ability of garlic to lower blood pressure, cholesterol, and blood clotting has been recognized for some time. There has actually been a surprising number of studies testing the ability of aged garlic extract to halt heart disease progression. For example, in a study published in early 2016 that used baseline and follow-up CT angiograms of heart arteries, aged garlic extract reduced areas of plaque in heart arteries at the one-year follow-up. Aged garlic has also been shown to inhibit coronary calcification progression in human randomized studies.9

Pomegranate. Pomegranate juice and seeds both have powerful antioxidant properties that may improve the function of HDL cholesterol. This protective cholesterol may boost the reverse cholesterol transport, or “vacuum cleaner” function in arteries, that may reverse CAD. In a study using pomegranate juice for three years in human subjects, the degree of narrowing in carotid arteries of five study subjects was reduced.10

Chelation therapy. Over 60 years ago some data surfaced that chelation therapy (Latin for claw) using disodium ethylene diamine tetra acetic acid (EDTA) could reverse heart artery disease. It took many decades but the Trial to Assess Chelation Therapy (TACT) was published in 2013 and demonstrated an improvement in outcomes in post-myocardial infarction (MI) patients following IV EDTA versus a placebo. The TACT showed a particularly large reduction in CVD events and all-cause mortality in the subgroup of patients with diabetes. An ongoing TACT 2 study limited to patients with heart disease and diabetic mellitus type 2 is further examining this unique therapy in the hope that it may enter the armamentarium to reduce the atherosclerotic risk of their diabetic patients. I reviewed in detail all the current data on chelation therapy and cardiovascular disease in the December 2021 edition of the Townsend Letter.11

Other Nutraceuticals for Reversal

Bergamot citrus superfruit grows in southern Italy and has many bioactive chemicals that lower cholesterol, inflammation, and blood sugar. Bergamot was studied in patients with atherosclerosis over six months without randomization.12 Lipid fractions improved as anticipated during therapy with bergamot, and there was a stunning decrease in the CIMT from 1.2 cm to 0.9 cm.

Vitamin E has eight forms and four of them are classified as tocotrienols with properties far more favorable than the more common tocopherols. In a study of 50 patients with carotid disease, half were treated with a source of gamma tocotrienol from palm oil. Over 18 months of therapy, regression of plaque was seen in 7 of the 25 patients treated with the vitamin E preparation while in the control group none regressed and 10 showed worsening.13

A promising combination therapy has been reported to promote the reversal of carotid atherosclerosis. The study combined Pycnogenol (French maritime pine bark) with Centella asiatica and followed 391 patients with ultrasound measurements of plaque for over four years in a randomized trial. The progression of plaque over time was least in the patients treated with the combination nutraceutical, and there was reduction in the number of angina episodes and myocardial infarctions in the treated cohort.14 

The same research team In Italy evaluated the efficacy of the Pycnogenol-Centella combination in asymptomatic atherosclerotic patients with coronary artery calcifications.15 The study included three groups of 30 men each with asymptomatic coronary artery calcifications. All subjects received standard diet, exercise, and lifestyle counselling, and took daily aspirin.

The first group received no additional treatment. The second added 150 mg/day of Pycnogenol. The third used the combination of 150 mg/day pine bark and 450 mg/day of Centella asiatica extracts. After one year, there was a 35% increase in the number of coronary artery calcifications in the group that received diet, lifestyle, and exercise counselling plus aspirin. In those taking Pycnogenol alone new calcifications were halted. In those using the combination herbal supplement there was a 10% decrease in the number of calcifications, a remarkable result I have reproduced in my preventive clinic.

The Italian research team went on to evaluate the impact of the combination of Pycnogenol and Centella asiatica extracts on atherosclerotic plaque progression in heart arteries that had received stent placement for severe blockages.  In 160 stented patients with partial arterial blockage due to atherosclerotic changes (as determined by ultrasound) were grouped into one of three treatment arms.16 The study began 6-10 months after successful stent procedures, and patients were followed for 12 months. After 12 months of follow-up, progression of atherosclerotic lesions on inner coronary artery walls occurred 6.7 times more patients in the diet, exercise, lifestyle, and medication only group compared to the group that also received the combined Pycnogenol and Centella extracts. There was a significant reduction in oxidative stress in the group of patients receiving the combination therapy. No side effects or tolerability problems were observed with the plant extracts.

Recently a study of a green algae extract in a capsule given twice a day for two months was examined in terms of impact on the “lipid rich necrtoic core” of carotid plaque using MRA to assess the arteries before and after. The preliminary findings of this ongoing study in China indicated a significant decrease of 50% or more in this measure of disease and provides a hopeful avenue of therapy by emphasizing the endothelium and its glycocalyx.17 More patients need to be studied before concluding the value of this approach.

A nutraceutical that is commonly used by practitioners is L-carnitine. A recent study examined the impact of this supplement on the progression of atherosclerosis.18 In 157 patients with metabolic syndrome, a randomization to 2 grams daily of L-carnitine or placebo was used for 6 months. The amount of carotid stenosis measured by ultrasound studies increased in the L-carnitine arm and not the placebo group. The researchers warned about further use of L-carnitine outside of clinical trials and its role in raising levels of TMAO, a metabolite described as having adverse cardiovascular outcomes.

Atherosclerosis remains the number one killer of men and women in the Western world. Primordial prevention of atherosclerosis from childhood on by emphasizing healthy lifestyles and early lab work for detection of genetic inheritances like familial hyperlipidemia and lipoprotein(a) is ideal. For those with subclinical or overt atherosclerosis, there is hope that even for patients with advanced disease, nutrition, pharmacology, and nutraceutical therapies can improve their quality and quantity of life by inducing regression of atherosclerosis.


References

  1. Morrison LM. Reduction of mortality rate in coronary atherosclerosis by a low cholesterol-low fat diet. Am Heart J 1951 4:538-545.
  2. Pritikin N. The Pritikin Diet. JAMA 1984 251(9):1160-1.
  3. Ornish, D et al. Intensive lifestyle changes for reversal of coronary heart disease. JAMA 1998 280(23):2001-7
  4. Esselstyn CB. A plant-based diet and coronary artery disease: a mandate for effective therapy J Geriatr Cardiol 2017 (5):317-320.
  5. Galiuto L et al. Efficacy of a Mediterranean diet for the secondary prevention of cardiovascular disease. European Heart Journal 2022 43:2727–2728
  6. https://www.acc.org/latest-in-cardiology/journal-scans/2021/08/16/17/34/mediterranean-diet-reduces-atherosclerosis
  7. https://www.medscape.com/viewarticle/784564
  8. Mitchell JD et al. Impact of Statins on Cardiovascular Outcomes Following Coronary Artery Calcium Scoring J Am Coll Cardiol 2018 72 (25) 3233–3244.
  9. Wlosinska M et al. The effect of aged garlic extract on the atherosclerotic process – a randomized double-blind placebo-controlled trial. BMC Complement Med Ther 2020 29;20(1):132.
  10. Davidson MH et al. Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease Am J Cardiol 2009 104(7):936-42.
  11. Kahn J. Chelation therapy in cardiovascular disease: an update on the science. Townsend Letter 2021 461:32-35.
  12. Toth PP et al. Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study. Front Pharmacol 2016 6;6:299.
  13. Tomeo AC et al. Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids.  1995 30(12):1179-83.
  14. Belcaro G et al. Pycnogenol(R) and Centella asiatica to prevent asymptomatic atherosclerosis progression in clinical events. Minerva Cardioangiol. 2017 Feb;65(1):24-31.
  15. Hu S et al. Central cardiovascular calcifications: supplementation with Pycnogenol(R) and Centellicum(R): variations over 12 months. Minerva Cardioangiol. 2020 Feb;68(1):22-6.
  16. Belcaro G et al. Pycnogenol(R)+ Centellicum(R), post-stent evaluation: prevention of neointima and plaque re-growth. Minerva Cardioangiol. 2019 Dec;67(6):450-5.
  17. https://f.hubspotusercontent20.net/hubfs/7072026/Arterosil%20Research%20Study%20Summary.pdf
  18. Johri AM et al. Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome. Nutr Metab 2022 2;19:26

 Published May 20, 2023


About the Author

Joel Kahn, MD, FACC, is an integrative cardiologist. He is the founder of Kahn Center for Cardiac Longevity and is a clinical professor of medicine at Wayne State University School of Medicine.

The Kahn Center for Cardiac Longevity in Bingham Farms, Michigan, is one of the world’s premier cardiac clinics. Joel Kahn, MD, and his team offer advanced care using a direct patient model — you have exclusive access to Dr. Kahn, longer and more thorough consultations, and access to the most advanced preventive screenings.

One of the clinic’s sought-after services is a one-on-one thorough evaluation with Dr. Kahn. It’s called the Ultimate Heart Check Up. Additional services at the clinic include Carotid Intimal Medial Thickness (CIMT) ultrasounds, EndoPat (peripheral arterial tone) artery health screenings, advanced labs, calcium scores, genetic testing, and nutrition counseling.

Driven by a passion to help people live as long as possible, Dr. Kahn is an ardent believer in educating his patients to become “Young at Heart by Design,” his proven program to help men and women live younger, feel younger, and stay younger.

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If you’re ready to take control of your heart health, reach out to the Kahn Center for Cardiac Longevity to make an appointment or use the online scheduler.