Guest Post by Kirsten Halbrich Oudin, ASN’s Dietetic Intern

I am a dietetic intern with the American Society for Nutrition for the month of February 2019. February also happens to be National Cancer Prevention Month which hits very close to home because my father lost his battle with lung cancer in November 2016 at 61 years young. It is kismet that my rotation lined up with this month’s blog entry on the linkages between nutrition and cancer, specifically related to prevention and adverse reactions to treatment. As an aspiring Registered Dietitian, I heavily researched diets to help my dad as he went through the difficult diagnosis and treatment. What I found was that every cancer is different, that’s obvious; however, no matter the type of cancer, mechanism of onset, or even genetic predisposition, a well-balanced diet, coupled with regular exercise, is paramount for cancer prevention as well as treatment.

Nutrition for Cancer Prevention

According to the World Health Organization, “between 30–50% of cancers can currently be prevented by avoiding risk factors and implementing existing evidence-based prevention strategies.” Among these evidence-based strategies are the 2012 American Cancer Society (ACS) Guidelines for Cancer Prevention which have a strong correlation between increased adherence to diet recommendations and decreased cancer mortality. See below for detailed diet recommendations.

2012 ACS Guidelines – Nutrition Recommendations for Individual Choices:

  1. Consume a healthy diet with an emphasis on plant foods.
    1. Choose foods & beverages in amounts that help achieve & maintain a healthy weight.
      • Read food labels to become more aware of portion sizes & calories consumed. Be aware that “low fat” or “nonfat” does not necessarily mean “low calorie”.
      • Eat smaller portions of high-calorie foods.
      • Choose vegetables, whole fruits, and other low-calorie foods instead of calorie-dense foods such as French fries, chips, ice cream, doughnuts, and other sweets.
      • Limit consumption of sugar-sweetened beverages (soft, sports, & fruit-flavored drinks).
      • If eating out, select foods lower in calories, fat & added sugar and avoid large portion sizes.
    2. Limit consumption of processed meats & red meats. *Consumption of processed meats and meats preserved by methods involving smoke or salt increases exposure to potentially carcinogenic chemicals, and therefore should be minimized.
      • Minimize consumption of processed meats such as bacon, sausage, lunchmeats, and hot dogs.
      • Choose fish, poultry, or beans as an alternative to red meat (beef, pork, and lamb).
      • If you eat red meat, select lean cuts & eat smaller portions.
      • Bake, broil or poach meats, poultry and fish instead of frying or charbroiling.
    3. Eat at least 2.5 cups of vegetables & fruits each day.
      • Include vegetables & fruits at every meal and for snacks.
      • Eat a variety of vegetables & fruits each day.
      • Emphasize whole vegetables & fruits; choose 100% juice if you drink vegetable or fruit juices.
      • Limit consumption of creamy sauces, dressing, and dips with vegetables & fruits.
    4. Choose whole grains instead of refined grain products.
      • Choose whole-grain foods such as whole-grain breads, pasta, cereals (barley & oats) instead of those made from refined grains; and brown rice instead of white rice.
      • Limit consumption of other refined carbohydrate foods, including pastries, candy, sugar-sweetened breakfast cereals, and other high-sugar foods.
    5. If you drink alcoholic beverages, limit consumption.
      • Drink no more than 1 drink per day for women or 2 per day for men.

Nutrition During Cancer Treatment

There have never been so many different options of cancer treatments available from chemotherapy, radiation and surgery to immunotherapy, hormone therapy and clinical trials. With additional treatment options comes the potential for additional side effects. Many of these side effects can be combatted with appropriate diet therapy. The main nutrients to focus on during cancer treatment are protein, carbohydrates, fats, water, vitamins & minerals. Protein needs often increase to support muscle strengthening and maintenance for resisting infections, recovering from illnesses, and repairing tissues. Carbohydrate sources are essential, choosing whole grains and complex carbs over empty carbs and sweets promote sustainable energy and nutrient-dense foods. Fat sources of “healthy” mono- and polyunsaturated fats over “unhealthy” saturated and trans fats promote heart health and cholesterol management. Water is vital, especially if experiencing vomiting or diarrhea, often increasing fluid needs beyond the standard 64 fluid ounces daily to maintain homeostasis and replenish cellular health. Fluid needs are not limited to water and may include soup, broth, milk and gelatin. Vitamin & mineral needs may also increase, especially if experiencing decreased appetite, making multivitamins or mineral supplements suitable alternatives for sources of the essential nutrients the body systems need to promote energy.

*Consult a Doctor and/or Registered Dietitian before adding supplements or altering diet in any way. Type of cancer, diagnosis, prognosis and treatment are critical for determining appropriate dietary action.

Emerging Cancer Nutrition Research

There are many emerging trends, evolving research, fads and fables circulating around the role nutrition plays in relation to cancer. Some of these are unsupported rumors with little to no evidence to back them up such as the myth that coffee is directly related to an increased risk of cancer and therefore requires a “May cause cancer” disclaimer at certain coffee shops. Another common misconception is that dietary supplements are equivalent to whole food sources; however, particularly with regards to cancer prevention, antioxidants, vitamins & minerals should ideally be consumed as part of the diet (if possible). The chart below briefly reviews additional food items thought to effect cancer risk.

Food Category Increased Risk of Cancer? Reduced Risk of Cancer? Additional Info
Nonnutritive Sweeteners & Sugar Substitutes Inconclusive X Safe when consumed in moderation
Pesticides & Herbicides Not in low doses found in most crops X Wash fruits & veggies before eating
Phytochemicals X Inconclusive Best ingested in whole foods, not supplements
Salt Inconclusive X Less salt cured/pickled food may prevent some cancers
Selenium X Inconclusive Thin line between safe & toxic dose (200 μg daily UL)
Soy Products X May reduce risk of breast, prostate, or endometrium cancers Traditional soy products (tofu) not isolated soy protein supplements
Sugar May indirectly increase cancer risk via obesity X Due to high caloric content and no nutritive value
Tea X Inconclusive Source of antioxidants, polyphenols and flavonoids
Trans Fats Inconclusive X Minimize intake for overall heart health
Turmeric & Other Spices X Inconclusive Rolling studies on turmeric, capsaicin, cumin and curry
Fruit & Veggies X May reduce risk of lung, mouth, pharynx, larynx, esophagus, stomach and colorectal cancers Specific anticancer compounds present in fruits and veggies are still unknown
Vegetarian Diets X Mixed findings: Yes in UK;

Inconclusive in US

May need to supplement B12, Zinc, Iron & Calcium
Vitamin A (supplement) High doses may increase lung cancer risk No Promotes tissue health
Vitamin C X Yes in food sources;

No in supplement form

Vitamin C rich foods are favored over supplements
Vitamin D X May reduce risk of colorectal cancer Many people in America do not get enough Vitamin D
Vitamin E (supplement) 1 study showed increased risk of prostate cancer No Not recommended to deter cancer or chronic diseases

Other Food Related Risk Factors:

  • Food Additives & Contaminants may increase the risk for certain types of cancers through agricultural exposure to growth hormones and endocrine disrupting chemicals such as bisphenol A and phthalates; unintentional chemical or environmental fungal contamination; and elemental carcinogen transfers through soil, water, and food supplies (i.e., heavy metal, cadmium, or mercury). The Food and Drug Administration (FDA) has declared that any new, intentional additives must be tested and cleared prior to public distribution.
  • Food Processing has both positive and negative effects on cancer risk. Freezing and canning can promote bioactivity in fruits and vegetables which decrease risk of certain cancers. However, refined grains have removed the dietary fiber that helps to lower cancer risk; and preserved meats with added salt and nitrites are higher in carcinogens, a known cause of cancer.
  • Microbial Food Safety involves food irradiation to reduce microbial contamination and food poisoning; although radiation is a known carcinogen it does not have the same effects on food as it does on a living person.
  • Organic Foods are not supported by evidence to be a better or worse choice than conventional foods so continue making vegetables, whole grains, and fruits the focus of all meals or snacks regardless of growth method.

Sample Recipes:

Professional Resources:


  1. Aune D, Keum N, Giovannucci E, et al. Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies. Am J Clin Nutr. 2018;108(5):1069-1091.
  2. Demark-Wahnefried W, Rogers LQ, Alfano CM, et al. Practical clinical interventions for diet, physical activity, and weight control in cancer survivors. CA Cancer J Clin. 2015;65(3):167-189.
  3. Goulão B, Stewart F, Ford JA, et al. Cancer and vitamin D supplementation: a systemic review and meta-analysis. Am J Clin Nutr. 2018;107(4):652-663.
  4. Jayedi A, Emadi A, Shab-Bidar S. Dietary Inflammatory Index and Site-Specific Cancer Risk: A Systematic Review and Dose-Response Meta-Analysis. Adv Nutr. 2018;9(4):388-403.
  5. Kim YI. Folate and cancer: a tale of Dr. Jekyll and Mr. Hyde? Am J Clin Nutr. 2018;107(2):139-142.
  6. Kushi LH, Doyle C, McCullough M, et al. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: Reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2012;62(1):30-67.
  7. McCullough ML, Patel AV, Kushi LH, et al. Following cancer prevention guidelines reduces risk of cancer, cardiovascular disease, and all‐cause mortality. Cancer Epidemiol Biomarkers Prev.2011;20(6):1089‐1097.
  8. Schoenfeld JD, Ioannidis JPA. Is everything we eat associated with cancer? A systematic cookbook review. Am J Clin Nutr. 2013;97(1):127-134.
  9. The American Cancer Society medical and editorial content team. Benefits of good nutrition during cancer treatment. Last Revised July 15, 2015.
  10. Cancer: Cancer Prevention. World Health Organization. 2019.
  11. Cancer: Key Facts. World Health Organization. 12 September 2018.
  12. International Agency for Research on Cancer. Cancer Fact Sheets: All Cancers. World Health Organization.
  13. International Agency for Research on Cancer. World Cancer Report 2014. World Health Organization.
Sweeteners_Sanae Ferreira

Sweeteners_Sanae Ferreira

In the case of Shakespeare, a rose is a rose is a rose – all smell sweet. But, in the case of sweeteners, the story is not quite so simple.


Here are a couple of scenarios that may look familiar to you:


– You’ve sat down at your favorite breakfast place, and your server has asked if you would like some coffee or tea while you consider the menu. A carafe appears, your cup is full, and you instinctively reach for the narrow box containing a rainbow of packets. You reach for one, but are curious about the rest – what are they really?

– You’re at the store, trying to buy something to drink, and there are words you don’t recognize on the label next to “sugar-free.”

Read more

Vitamin D, also known as cholecalciferol, plays an important role in bone health and muscle strength and is essential for the prevention of rickets (1). Cholesterol is a precursor of Vitamin D, which is endogenously produced in the body when ergosterol is exposed to UVB sunlight through the skin. It is also found in eggs, fatty fish and supplements (1).

A recent study by researchers in Japan found that higher levels of vitamin D may lower the risk of liver cancer. The study conducted by researchers at the Center for Public Health Sciences at the National Cancer Center in Tokyo suggests that people who suffer from low levels of Vitamin D may be at an increased risk for many different types of cancers; however the overall body of evidence is mixed (2,3).

This latest study was published in BMJ and explored biologically active forms of vitamin D in blood samples of over 30,000 middle-aged adults across Japan in the early 1990s. The follow-up for individuals was over a 16-year period. This analysis was based off a sample of 3301 participants who developed cancer during the study and 4044 randomly selected participants, of whom 450 developed cancer. The research team found higher levels of circulating vitamin D led to lower risk for cancers, overall, after controlling for age, sex, smoking status and family history of cancer. They also controlled for seasonal differences in circulating vitamin D. They did not find differences in the effect of vitamin D by sex; however, authors noted that participants in the lowest quartiles of vitamin D status had a 22% higher risk of cancer when compared to those in the highest quartiles. Additionally, they noted a 50% lower risk of liver cancers for those in the highest vitamin D group compared to the lowest, after adjusting for diet.

Vitamin D status was only measured at one point during follow-up, which serves as an important limitation. Additionally, inherent selection bias means that participants in the study may have been more health-conscious than the public at large. The number of rare cancer cases in the cohort was also small.

It is important to note that these latest findings apply primarily to Asian populations and higher levels of Vitamin D in these communities may lower risk for cancer; however, these findings cannot be translated across the board. It is important for those at risk of sun burns to avoid direct unprotected contact with the sun, which is a known risk factor for skin cancers. Additionally, lower levels of vitamin D may be an indication of poor health, overall (2,3).

Other health benefits of vitamin D have been seen in meta-analyses that have found a 31% reduction in falls among those supplemented with vitamin D. It also plays a role in improving the body’s response to infection among patients with cystic fibrosis (4). For populations in the US, vitamin D deficiency remains a problem in populations including African American communities, where according to the National Health and Nutrition Examination Survey (NHANES), 60% of people suffer from low levels (5,6). Through fortification of dairy products and supplementation, these numbers have reduced; however, greater attention including additional research is needed to reduce risk of deficiency, with added benefits to risk reduction for other health conditions, including cancers.


  • Khazai, N., Judd, S.E. & Tangpricha, V. (2008). Calcium and vitamin D: skeletal and extraskeletal health. Current Rheumatology Reports, 10(2), 110-117.
  • Budhathoki, S., Hidaka, A., Yamaji, T., Swada, N., Tanaka-Mizuno, S., Kuchiba, A., Charvat, H., Goto, A., Kojima, S., Sudo, N., Shimazu, T., Sasazuki, S., Inoue, M., Tsugane, S., Inoue, M., Tsugane, S., & Iwasaki, M. (2018). Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort. The British Medical Journal, 2018, 360.
  • Davis, N. The Guardian, Nutrition. (2018) Retrieved from:
  • Pincikova, T., Paquin-Proulx, D., Sandberg, J.K., Flodstrom-Tullberg, & M., Hjelte, L. (2017). Clinical impact of vitamin D treatment in cystic fibrosis: a pilot randomized controlled trial. European Journal of Clinical Nutrition, 71, 203-205.
  • Jain, R.B. (2016). Recent Vitamin D data from NHANES: Variability, trends, deficiency and sufficiency rates and assay compatibility issues. Journal of Advanced Nutrition and Human Metabolism, 2.
  • Avenell, A., Mak, J.C., & O’Connell, D. (2014). Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database of Systematic Reviews, 14(4).

Lifestyle interventions targeted at obtaining/maintaining a healthy body weight and/or incorporating physical activity and healthy eating habits have great potential in improving outcomes in cancer survivors. Cancer diagnosis is a “teachable moment” wherein many patients are highly motivated to make changes (1). Furthermore, a balanced diet and moderate exercise can improve prognosis, quality of life, physical function, and survival across the cancer continuum. As such, groups such as the Amercian Cancer Society, National Comprehensive Cancer Network and the American College of Sports Medicine have released lifestyle guidelines for cancer survivors.

However, implementing changes in individuals and healthcare systems is challenging, to say the least. This is a recent topic covered by Karen Basen-Engquist and a number of colleagues as part of a special Issue of Obesity (Transdisciplinary Research on Energetics and Cancer)(2). Their article provides a 6-point agenda for translating research into clinical and community action, as follows:

  1. Increase the availability of different types of activities for weight management, nutrition counseling, and physical activity. One size will never fit all when it comes to improving health. Individual goals/preference, resources, and logistics all come into play, and cancer-specific programs may be needed.
  2. Improve screening and referral to lifestyle interventions. A system for evaluating and triaging patients for health programs should be developed. Importantly, an individual’s physical status, health needs, and goals should be considered.
  3. Improve the health care provider’s ability to screen, assess, and refer survivors for lifestyle programs. Oncology providers have a powerful role in helping cancer survivors; however, they often do not feel confident in screening, giving advice, or administering recommendations for lifestyle-related constructs. Implementation of processes such as the 5As (Ask, Advise, Assess, Assist, Arrange), which has been successful in tobacco cessation (3) and obesity management (4) might prove beneficial.
  4. Expand the support of oncology-specific professional training and certification. Professional organizations of dietitians, exercise professionals, psychiatrists, and physical therapists have additional certification programs for oncology or are working on developing one for its members. However, professionals with specific expertise in oncology are still greatly needed to address the unique needs of this population.
  5. Expand dissemination and implementation research. Many research programs do not address how a program could be implemented in a real-world setting (external validity). Dissemination of research findings with consideration of the sustainability and generalizability of programs is essential for broader impact.
  6. Advocate for health care policies that support lifestyle services for cancer survivors. Coverage for health programs is highly variable and often has barriers such as large co-payments, no coverage in grandfathered plans, and cost sharing. A potential solution could be incentivizing nutrition and exercise services, although more research is needed to determine the effectiveness of such actions.

As the authors eloquently articulate, the time has come to enable research into action for optimal healthcare in all cancer survivors.


  1. Demark-Wahnefried W, Aziz NM, Rowland JH, Pinto BM. Riding the crest of the teachable moment: promoting long-term health after the diagnosis of cancer. J Clin Oncol 2005;23:5814–30.
  2. Basen-Engquist K, Alfano CM, Maitin-Shepard M, Thomas CA, Schmitz KH, Pinto BM, et al. Agenda for Translating Physical Activity, Nutrition,and Weight Management Interventions for Cancer Survivors into Clinical and Community Practice. Obesity 2017; 25, S9-S22.
  3. Siu AL, Force USPST. Behavioral and pharmacotherapy interventions for tobacco smoking cessation in adults, including pregnant women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2015;163:622-634.
  4. Rueda-Clausen CF, Benterud E, Bond T, Olszowka R, Vallis MT, Sharma AM. Effect of implementing the 5As of Obesity Management framework on provider-patient interactions in primary care. Clin Obes 2013; 4, 39-44.


By Caitlin Dow, PhD

If you’ve spent any time on the internet in the last couple of months, you’ve likely heard about the recent statement on red and processed meat from the World Health Organization (WHO).The statement was produced by a Working Group of 22 scientists who gathered together at the International Agency for Research on Cancer (IARC), with the goal of considering all data from over 800 epidemiological studies on red and processed meat in order to determine their potential carcinogenicity. The group defines red meat as “mammalian muscle meat – such as beef, veal, pork, lamb, mutton, horse, or goat” and processed meat as “meat that has been transformed through salting, curing, fermentation, smoking, or other processes to enhance flavour or improve preservation” (1). Based on the available data, the Working Group concluded that “that there is sufficient evidence in human beings for the carcinogenicity of the consumption of processed meat.” And then the internet exploded. But what exactly does this mean?

The IARC is responsible for categorizing chemical compounds based on the strength of evidence that said chemical may be carcinogenic. In this statement, they categorized processed meat as a Group 1 carcinogen and red meat as a Group 2B carcinogen.These categorizations are used to describe the strength of evidence that these compounds may be carcinogens; thus, Group 1 is used to distinguish “established carcinogens” [e.g. acetaldehyde (a metabolite of alcohol), oral contraceptives, formaldehyde, and sawdust], whereas Group 2B includes compounds that are considered “possible carcinogens” [e.g. benzofuran (a compound in coal tar), butylated hydroxyanisole (an additive found in foods, cosmetics, rubber, etc.)] (2).And while these classifications are important, they are easily misconstrued, as was the case in this statement by the IARC. These classifications simply tell us that a compound could be hazardous to human health. What they don’t tell us is degree of risk.That’s important because lots of things can be hazardous without posing a significant risk.For example, UV radiation is a hazard, but it is only a risk if one is exposed to excessive amounts of UV radiation.That is, risk is the product of hazard multiplied by exposure. Reduce your exposure, reduce your risk. That’s where most people got confused with this IARC statement.

The media jumped on the statement and let out a warcry against red and processed meats.But what most of them failed to mention is the all-important question: how much red and processed meat need be consumed to increase risk for developing cancer? One meta-analysis found that risk of colorectal cancer increased with increasing intake of red and processed meats up to 140 g/day (~5 oz/day) (3). Further, risk of developing colon cancer in response to consuming red/processed meat increases by ~25% for every additional 100g consumed/day. Thus, this study was evaluating risk in consumers who eat A LOT of red and processed meats.Importantly, these effects were strongest in European (29% elevated risk/100 g/day increase in intake) compared to North American (11% elevated risk/100 g/day increase in intake) and especially to Asia-Pacific studies that observed a non-significantly reduced risk (6% reduced risk/100 g/day increase in intake). These results indicate that not all populations are equally affected, which is likely due to differences in genetics and/or lifestyle. And what about people who don’t even eat red/processed meat everyday? Are they at risk just by eating these foods once in awhile? A meta-analysis by Norat, et al. (4) estimated that reducing red meat consumption to 70 g/week (~one 3 oz. serving/week) would reduce colorectal cancer rates by 7-24% in regions with high intake.That is, eating red or processed meat once a week likely does not increase risk for colorectal cancer.

At the end of the day, the IARC added processed and red meat to their list of carcinogens.But in terms of translating that into a public health message, they didn’t do a great job.Yes, red and processed meats are hazards to health. If you choose to eat them, keep your exposure low and your risk will likely also be low. As always, eat a varied diet, high in fruits and vegetables, whole grains, legumes, nuts and seeds to ensure high antioxidant and anti-inflammatory compound intake to protect against potential damage that red and processed meats may pose.


1.Bouvard, et al. on behalf of the International Agency for Research on Cancer Monograph Working Group.Carcinogenicity of consumption of red and processed meat. Lancet: Oncology. 2015 Dec;16(16):1599-1600.

2.American Cancer Society. Known and Probably Human Carginogens. 2015 Oct.

3.Chan DS, et al. Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies. PLoS One. 2011;6(6):e20456.

4.Norat T, et al. Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies. Int J Cancer. 2002 Mar;98(2):241-56.

By Brett Loman

Nutrition may be a relatively young science, but perhaps the intuition of our elders has informed us more than we realize. Food superstitions are as old as culture itself and essentially every civilization has added its share to the ever-growing list of dos and don’ts. In respect to two months in a row with Friday the 13ths this year, I investigated how some long-standing tales about what we eat might actually be grounded in truth.

Spilling salt brings bad luck. This widely recognized superstition originating in ancient Greece may hold some hidden truths. One of the most commonly believed concepts about sodium (salt) today is that eating too much can aggravate conditions such as hypertension, cardiovascular disease, and chronic kidney disease. The American Heart Association and National Kidney Foundation recommend limiting salt consumption to about 1,500 mg/d. So whether you believe the superstition or modern medicine, you will think twice and shake the habit of spilling salt onto your meal.

Eating garlic, onions, and mustard seeds is good luck by granting blessings or warding off evil. This superstition is rooted in many proverbs, and it just so happens that vegetables in the Amaryllis (onions, garlic, etc) and Brassicaceae (mustard, broccoli, etc) families are being investigated as anticarcinogens. Many of the naturally occurring phytochemicals in these plants may serve to halt the formation of cancer causing compounds, enhance repair of damaged DNA, and induce apoptosis of tumor cells. Chowing down on these luckily talismans could ward off disease, but don’t forget that those same beneficial compounds may also scare off your friends with the odors they leave lingering behind.

Bringing bananas on a boat will cause fishermen ill will and a bad catch. Green bananas, coincidentally, may just cause some unwanted symptoms of illness. Un-ripened bananas are a good source of resistant starch. Depending on your personal disposition, fermentation of resistant starch could either provide a healthy dose of short-chain fatty acids to the intestines, or a healthy dose of gas and diarrhea. Any angler would have difficulty landing the big one between frequent trips to the loo, and that’s no fish tale.

Planting parsley will help a woman become pregnant. Of course having good nutrition is important for increasing chances of beginning a pregnancy, but parsley is specifically of interest for the health of the newly developing fetus. This ubiquitous herb is a good source of many vitamins and minerals, including folic acid. In the first few weeks, adequate folate is especially important for preventing neural tube defects in the rapidly growing baby. Consider sowing seeds of parsley before sowing your wild oats.

Every day we find out more and more about how our eating habits affect our bodies, but in some cases we shouldn’t overlook what prior generations have already provided us. Tell the researchers and your grandma thanks for the advice.

1. Cobb, L.K., Anderson, C.A.M., Elliott, P., et al. Methodological issues in cohort studies that relate sodium intake to cardiovascular disease outcomes: A science advisory from the American Heart Association (2014) Circulation, 129 (10), pp. 1173-1186.