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Heart Health and Chronic Inflammatory Disorders

Adapted from a presentation to the HSS Myositis Support and Education Program by Erica C. Jones, MD, FACC, on October 9, 2018

(Although this information was presented at a support group for people with myositis, it is also helpful for people with other inflammatory conditions, such as rheumatoid arthritis and lupus. The content of this summary may be used as a general guideline. However, any individual concerns should be discussed with your doctor.)

Risk Factors for Cardiovascular Disease

It is important to understand the general risk factors for cardiovascular disease (CVD) and that there are some differences in these between men and women. Risk prediction is not a perfect science, Dr. Jones stated, but there are traditional risk factors for both men and women.

Risk factors that cannot be changed

  • Age
  • Being male: Men develop heart disease about 10 to 15 years earlier than women. On CT scans, about 50% of white men have evidence of calcified plaque by age 53, and for women, it is at age 65 (a bit less bit less among black, Hispanic, and Asian populations).
  • Family history of CVD

Risk factors that can be changed

  • Smoking
  • Diabetes
  • Hypertension (high blood pressure)
  • Lack of exercise
  • High cholesterol
  • Obesity
  • Depression

Nine risk factors account for 90% of heart attacks worldwide
(The numbers in parentheses show the percentage of risk that each factor represents)

  • Elevated LDL cholesterol (49%)
  • Smoking (36%)
  • Stress (33%)
  • Abdominal fat (20%)
  • Hypertension/high blood pressure (18%)
  • Too few fruits and vegetables in daily diet (14%)
  • Lack of exercise (12%)
  • Diabetes (10%)
  • Alcohol (7%)

Other cardiovascular risk factors that have been identified more recently

  • Chronic inflammatory disorders
  • Prior radiation/chemotherapy
  • Pregnancy complications
  • HIV
  • Migraine headaches
  • Sleep deprivation/sleep apnea
  • Depression (which can include social isolation, lack of sense of purpose, anger, and pessimism)
  • Chronic emotional stress

The calculations to determine risk of developing atherosclerotic cardiovascular disease (ASCVD) established in 2013 by American College of Cardiology/American Heart Association include: age, sex, race, total cholesterol, HDL (“good”) cholesterol, systolic (top number) blood pressure, hypertension, diabetes, and current smoking.

When risk is high, the recommendation most often is for use of a statin, possibly with other medications.

However, these guidelines assess risk for those between ages of 40 and 79 and who have not had an ASCVD incident. In addition, this does not take into account family history, coronary artery calcium (seen on a CT scan), inflammatory/autoimmune disorders, and complications during pregnancy.

Additional factors missing from the guidelines to assess risk factors is that it includes only non-Hispanic white and black individuals. It is difficult to know, then, if risk is being over- or underestimated.

The good news, however, is that the use of statins over the last 20 to 30 years has resulted in an overall decrease in CVD deaths.

With relation to cardiovascular disease, there are some differences between men and women. Estrogen in women can be seen as a protective factor against heart disease, and the loss of estrogen at menopause increases the risk of developing heart disease. Throughout the 15 years after menopause, the risk for men and women equalizes.

Dr. Jones went on to say that there are some sex differences in the pathophysiology of plaque (what the plaque actually looks like when examined under a microscope or on CT scan, and how these plaques cause a heart attack). For example, when women experience chest pain symptoms, they more often have plaque that is not occluding (obstructing) the artery and may have higher risk of disease in the very tiny vessels in the heart (microvascular disease). Women are also at higher risk of developing a stress- induced cardiomyopathy (when the heart suddenly weakens after severe emotional stress).

Heart Attack (Myocardial Infarction) Symptoms

Classic symptoms in both men and women

  • Angina is defined as chest pain or discomfort that comes on with exertion and is relieved by rest and/or use of nitroglycerin (which dilates the vessels to allow more blood flow)
  • Chest pain at rest lasting more than 30 minutes and not relieved by nitroglycerine is concerning for a heart attack
  • Common associated symptoms
    • Pain that travels to the jaw or teeth
    • Pain that travels to the back

Many people do not have the above symptoms, so attention should also be given to the following

  • Unexplained sweating
  • Indigestion
  • Nausea/vomiting
  • Unexplained sense of doom
  • Extreme fatigue, lightheadedness, dizziness

Heart attack symptoms specific to women

In both men and women, the most common symptom of a heart attack is chest pain. There are, however, some important differences:

  • Women may have different triggers and distribution of non-chest related symptoms such as:
    • Abdominal or epigastric discomfort and nausea
    • Radiation of pain to arms, neck, and back
    • Shortness of breath and fatigue
  • Compared to men, symptoms in women are more often brought about by mental or emotional stress as opposed to exertion (although exertional symptoms are still most common in both)

Many people ignore the signs and symptoms of a heart attack. Dr. Jones emphasized the importance of taking chest pain, as well as the other, lesser-known symptoms listed above, seriously. The message is that you should always go to the emergency room with chest pain.

Better Ways to Predict Risk

Dr. Jones went on to discuss the clinical impact of inflammation on atherosclerosis (hardening of the arteries, which can lead to cardiovascular disease). Blood levels of markers hsCRP (c-reactive protein) and IL-6 (interleukin-6) can also predict first and recurrent cardiac events, no matter what the cholesterol level is. A very well-known study in the cardiovascular literature, called Justification for the use of Statin in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)2,3, showed us that:

  • Statins lower LDL and are anti-inflammatory
  • Those who did best on a statin achieved a lower LDL and a decreased hsCRP
  • Those with elevated hsCRP and normal LDLc benefited markedly from statin therapy
  • From JUPITER and subsequent studies, we know that high-risk patients can have “residual cholesterol risk" (those whose cholesterol does not get to low levels with treatment) and “residual inflammatory risk” (those who achieve excellent cholesterol lowering but have continued higher inflammatory markers)

Lowering LDL With Statins: What Do People Fear?

Statins are a group of drugs that lower cholesterol (specifically, LDL) and to a lesser degree, triglycerides in the blood. Dr. Jones stated that true statin toxicity is very rare and is often associated with interactions with other medications. However, use of statins has been associated with the onset of myositis in some cases4,5,6,7,8. It is understandable, then, that patients patients with myositis or underlying muscle disease might be concerned about using them.

Those who might have greater risk of statin-induced muscle symptoms include:

  • People with predisposing factors:
    • History of increased creatine kinase (CK) levels
    • Family history of myopathy
    • Prior diagnosis of neuromuscular disease
    • Hypothyroidism
    • Genetic risk factors, such as SNP in SLCO1B1 gene
    • Underlying myositis
  • Use of high-dose statin
  • Advanced age
  • Use of other drugs that interfere with stain metabolism

The following provides some research on the link between statins and myositis. Numerous studies in patients with true muscle damage (necrotizing myopathy) found that, in people who developed true muscle damage:

  • Symptoms did not resolve when statins were discontinued
  • Patients were treated with steroids and immunosuppressants
  • The link between statins and muscle toxicity was at first difficult to prove

However, there are now registries that have helped provide more data.

Statin Exposure and Myositis8

This was a study involving 221 patients with myositis who had been using a statin. It was found that there was a 79% increased likelihood of statin exposure in patients with myositis when compared with the control group (those who did not use statins).

The breakdown by types of myositis seen:

  • 89 with polymyositis
  • 66 with inclusion body myositis
  • 23 with dermatomyositis
  • 24 with necrotizing myositis
  • 19 with nonspecific chronic inflammatory myositis

Alternatives to Statins to Lower LDL Cholesterol*

  • PCSK-9 inhibitors: monoclonal antibodies developed for people in whom other treatments have not been effective. Current FDA approved are: alirocumab (Praluent) and evolocumab (Repatha). These are injectables and are quite costly.
  • Fibrates: are used only for extremely elevated triglyceride (blood fat) levels. They can raise HDL (good cholesterol) but have minimal, if any, effect in lowering LDL (bad cholesterol).
  • Omega-3 Fatty Acids: the debate on their efficacy continues. Dr. Jones noted that it is preferable to get fatty acids through food. The following fish contain Omega-3: mackerel, trout, herring, sardines, albacore tuna and salmon.
  • Ezetimibe (Zetia): Blocks absorption of cholesterol from the small intestines. It is best used in combination with a statin, but if a statin is not an option, alone it can lower LDL 20% to 30%.

Recommended treatments that include natural approaches to reducing cholesterol

Please be aware that any treatment you consider should first be discussed with your doctor and that studies on lowering cardiovascular events are lacking. Two recent reviews9,10 are well-organized resources and understandable to readers without a medical background.

Certain nutraceuticals (foods that may provide a health benefit in addition to basic nutritional value) can help lower LDL levels alone, in combination with each other, as well as an addition to ezetimibe (zetia) and might be considered as an add-on, or alternative to, statin therapy. However, there is still not enough evidence to determine long-term safety and effectiveness on cardiovascular disease and treatment.

Dr. Jones provided a list of supplements and nutraceuticals that can lower cholesterol:

  • L-reuteri: Dr. Jones cited a review that looked at 26 clinical studies and two meta-analyses. L.reutieri is found in both yogurt and capsules. It was found that L-reuteri greatly lowers LDL cholesterol and total cholesterol when compared with placebo. It was further noted that “L.reuteri improved other coronary heart disease factors, such as inflammatory biomarkers and was given the ‘generally regarded as safe’ (GRAS) status.”11
  • Beta-glucan: a yeast polysaccharide that swells after ingestion, forming a gel that binds cholesterol to prevent its absorption.
  • Soluble fibers (oats, guar gum, pectin, psyllium) and glucomannan can both lower both cholesterol and glucose.
  • Berberine: a natural alkaloid found in plants of the Berberis species; it has been found to lower cholesterol and triglycerides and improve insulin sensitivity. Its effects may be similar to how statins and PCSK-9 inhibitors work.
  • Bergamot: contains several flavonoids known to lower cholesterol.
  • Curciminoids: considered lipid lowering and anti-inflammatory and appear to be safe.12
  • Red yeast rice: this is a fermented yeast product that contains monacolin K, which is identical to lovastatin (a statin cholesterol-lowering drug). Because it contains very small amounts of “statin” Dr. Jones does not recommend it in people with myositis.

Dr. Jones stated that caution needs to be exercised when considering the use of supplements and nutraceuticals as they are not approved by the Food and Drug Administration (FDA). Some of the issues include:

  • Safety testing is not the same for all products
  • Amount of active ingredient may vary among supplements
  • Some contain ingredients not listed on the label
  • Supplements with the USP label contain 95 to 100% of active ingredient

Achieving Ideal Cardiovascular Health as Defined in the 2020 Impact Goal of the American Heart Association

  • Four health behaviors:
    • Do not smoke.
    • Maintain a healthy weight.
    • Develop a healthy eating pattern.
    • Remain physically active within your ability.
  • Three health factors:
    • Total cholesterol
    • Blood pressure
    • Nondiabetic

Dr. Jones spoke further on the highlights of the 2020 Impact Goal:

  • This is the first time that “ideal cardiovascular health” has been defined.
  • It is important, because it offers a scientific roadmap to assess meaningful data and results to achieve cardiovascular health.
  • From a scientific standpoint, it was recognized that there was a need to broaden the conversation beyond disease states and risk factors. We needed to include health behaviors and health factors.
  • The goal is to people prevent risk from developing at all, known as primordial prevention.
  • The new definition of cardiovascular health features a new emphasis on helping people move toward “ideal health.”
    • The measurements that have been identified emphasize moving the entire population, no matter the starting point of health, to a better level of cardiovascular health.

In conclusion, Dr. Jones said, “The 2020 goal is a significant milestone for the American Heart Association, and I know that thousands of science and research volunteers on our councils and our Boards and in our funded institutions are looking forward to meeting the challenges of our bold 2020 Goal.”

Learn more about the HSS Myositis Support Group, a free support and education group, held monthly for people with myositis, and their family and friends.

References

  1. Pooled data from 4 studies: Ambrose et al, 1988’ Little et al, 1968; Nobuyoshi, et al, 1991; and Giroud et al, 1992. (Adapted from Falk et al):
    Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R, Update on acute coronary syndromes: the pathologists' view. Eur Heart J. 2013 Mar;34(10):719-28. doi: 10.1093/eurheartj/ehs411. Epub 2012 Dec 13.
    Ambrose JA, Hjemdahl-Monsen CE, Borrico S, Gorlin R, Fuster V. Angiographic demonstration of a common link between unstable angina pectoris and non-Q-wave acute myocardial infarction. Am J Cardiol. 1988 Feb 1;61(4):244-7.
    Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988 Jul;12(1):56-62.
    Nobuyoshi M, Tanaka M, Nosaka H, Kimura T, Yokoi H, Hamasaki N, Kim K, Shindo T, Kimura K. Progression of coronary atherosclerosis: is coronary spasm related to progression? J Am Coll Cardiol. 1991 Oct;18(4):904-10.
    Giroud M, Boutron MC, Gras P, Gambert P, Lallemant C, Milan C, Essayagh E, Dumas R. Plasma lipoproteins in cortical versus lacunar infarction with or without cardiac arrhythmia, and in transient ischaemic attacks: a case control study.Neurol Res. 1992 Sep;14(4):315-20.
  2. Ridker PM A Test in Context: High-Sensitivity C-Reactive Protein. J Am Coll Cardiol. 2016 Feb 16;67(6):712-723. doi: 10.1016/j.jacc.2015.11.037.
  3. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207. doi: 10.1056/NEJMoa0807646. Epub 2008 Nov 9.
  4. Albayda J, Mammen AL. Is statin-induced myositis part of the polymyositis disease spectrum? Curr Rheumatol Rep. 2014 Aug;16(8):433. doi: 10.1007/s11926-014-0433-8
  5. SEARCH Collaborative Group, Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R.SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789-99. doi: 10.1056/NEJMoa0801936. Epub 2008 Jul 23.
  6. Christopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis 2010 Sep;62(9):2757-66. doi: 10.1002/art.27572.
  7. Mammen AL, Pak K, Williams EK, Brisson D, Coresh J, Selvin E, Gaudet D Rarity of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies in statin users, including those with self-limited musculoskeletal side effects. Arthritis Care Res (Hoboken). 2012 Feb;64(2):269-72. doi: 10.1002/acr.20662.
  8. Caughey GE,Gabb GM, Ronson S, Ward M, Beukelman T, Hill CL, Limaye V. JAMA Intern Med. 2018 Sep 1;178(9):1224-1229. doi: 10.1001/jamainternmed.2018.2859. Association of Statin Exposure With Histologically Confirmed Idiopathic Inflammatory Myositis in an Australian Population.
  9. Banach M, et al. The Role of Nutraceuticals in Statin Intolerant Patients. J Am Coll Cardiol 2018;72:96–118
  10. Johnston TP, Korolenko TA, Pirro M, Sahebkar A. Preventing cardiovascular heart disease: Promising nutraceutical and non-nutraceutical treatments for cholesterol management. Pharmacological Research 120 (2017) 219–225.
  11. DiRienzo DB. Effect of probiotics on biomarkers of cardiovascular disease: implications for heart-healthy diets. Nutr Rev. 2014 Jan;72(1):18-29. doi: 10.1111/nure.12084. Epub 2013 Dec 13. Review.
  12. Pagano E, Romano B, Izzo AA, Borrelli F. The clinical efficacy of curcumin-containing nutraceuticals: An overview of systematic reviews. Pharmacological Research 134 (2018) 79–91.
 

Summary by Suzan Fischbein, LCSW, Senior Social Work Coordinator.

Authors

Erica C. Jones, MD, FACC
Associate Professor of Clinical Medicine, Weill Cornell Medicine
Director, HeartHealth, The Cardiovascular Prevention Program, Dalio Institute of Cardiovascular Imaging

 

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