Zytiga May Up Mortality Risk in Prostate Cancer Patients With CVD


Zytiga May Up Mortality Risk in Prostate An increased risk of early death was observed in men with pre-existing cardiovascular disease (CVD) starting abiraterone acetate (Zytiga) for advanced prostate cancer, a registry study found.

Among abiraterone-treated patients, increased mortality ranged from 21.4% for those with ischemic heart disease to 25.6% for those with acute myocardial infarction (MI), compared with 15.8% for those without a heart condition, reported Grace Lu-Yao, PhD, MPH, of the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia.

“Our data show that patients with existing cardiovascular conditions experience significantly higher 6-month mortality than those without CVD,” Lu-Yao said during a media briefing ahead of the American Association for Cancer Research (AACR) meeting, to be held here March 29-April 3.

Of the 2,845 patients in the study, 67.6% had a pre-existing heart condition (n=1,924). Patients with atrial fibrillation, congestive heart failure, and stroke had increased mortality risks of 24.4%, 23.4%, and 22.1%, respectively, within these first 6 months.

“Typically clinical trials do exclude people who have significant medical problems,” said AACR President Elizabeth Jaffee, MD, of Johns Hopkins Medicine in Baltimore. “I think this has been rationalized as a safety measure by both investigators and sponsors.”

In her presentation, Lu-Yao highlighted that roughly 40% of prostate cancer patients have uncontrolled hypertension. These patients, plus those with a history of major heart conditions, are usually excluded from clinical trials. In the STAMPEDE study, for instance, exclusion criteria included those with a history of severe angina or heart failure, and those with a recent MI.

Jaffe noted that testing new agents in the healthiest patients does not provide the real-world data physicians need.

The researchers used Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data to look at prostate cancer patients treated with abiraterone from 2011 to 2014.

The study also found an increased risk of hospitalizations by examining hospital use in the 6 months before and after starting abiraterone treatment. Risk of hospitalization was increased for patients without a history of CVD for incidence rate ratios (IRR) 1.43 (95% CI 1.30-1.57), as well as for those with pre-existing CVD:

  • Acute MI: IRR 1.44 (95% CI 1.12-1.86)
  • Congestive heart failure: IRR 1.35 (95% CI 1.21-1.51)
  • Stroke: IRR 1.30 (95% CI 1.07-1.57)
  • Atrial fibrillation: IRR 1.27 (95% CI 1.09-1.48)
  • Ischemic heart disease: IRR 1.22 (95% CI 1.01-1.48)

The study captured the period from when abiraterone was first approved by the FDA in 2011 for use in late-stage castration-resistant prostate cancer after prior treatment with docetaxel, and when it was then expanded in 2012 to also include use before chemotherapy. In the study, roughly 20% of the patients had received prior chemotherapy (n=586), with the rest being chemotherapy naive. Lu-Yao said that regardless of prior chemotherapy use, the patterns for both early mortality and hospitalization were “quite similar.”

Jaffee noted that while the study is retrospective, it still provides important data, similar to that of a phase IV study.

“Once a drug’s approved, all physicians can administer these drugs, and we don’t really have a handle on who may have worse side effects from these drugs,” she said. “We know that all therapies have side effects, and we need to be able to predict early, screen early, so we can at least monitor for these side effects and intervene at an early stage before patients have severe consequences from these drugs.”

Study limitations included the possibility of misclassification of patients’ CVD, the fact that treatment efficacy could not be assessed, and that there was no control group to look at expected survival for this patient population. A lack of clinical data also meant that the researchers could not compare the study population against the pivotal trials of abiraterone acetate.

Anthocyanins are a colorful way to prevent cardiovascular disease


Image: Anthocyanins are a colorful way to prevent cardiovascular disease

It is often said that presentation is everything when it comes to meals, but there’s an even better reason to fill your plate with colorful foods. The pigment that gives foods like berries their rich red and purple hues also doubles as powerful protection against cardiovascular disease.

Studies have shown that this pigment, anthocyanin, not only offers antioxidant effects; it also protects people from chronic diseases. Indeed, one of its most impressive feats is lowering the risk of the cardiovascular conditions that take millions of lives each year, such as stroke, heart attack, and atherosclerosis.

In a systematic review that involved more than 600,000 participants, British researchers looked at the impact that dietary anthocyanins had on cardiovascular events. They discovered that those who had the greatest dietary anthocyanin intake enjoyed a 9 percent reduction in their risk of developing coronary heart disease; when it came to death due to heart disease, their risk was 8 percent lower compared to those who consumed the lowest amount of anthocyanin.

The study, which was published in Critical Reviews in Food Science and Nutrition, is the strongest argument yet for increasing your fruit intake. The Office of Disease Prevention and Health Promotion suggests that people eat a minimum of two servings of fruit per day; just 32 percent of Americans reach that goal.

Choose the right fruits

It’s easy to spot fruits that contain anthocyanins because of their red, purple and blue colors. Some of the best sources include strawberries, blackberries, grapes, pomegranates, cherries, blueberries, raspberries and bilberries. They can also be found in red cabbage, eggplant, and purple potatoes. It probably won’t come as much of a surprise to learn that the fruit’s skins contain the most anthocyanins given their rich color, so make sure you also eat the skin – and be sure to choose organic to avoid pesticide exposure. The review’s authors say that just one to two portions of berries per day are enough to get the anthocyanins you need to protect your heart.

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Anthocyanin’s many benefits

The review is supported by several other studies, including one from 2012 that was published in the American Journal of Clinical Nutrition. That study showed a link between a higher intake of anthocyanin and significantly lower systolic blood pressure, arterial pressure, and pulse wave velocity. It also confirmed an earlier study that showed eight weeks of taking blueberry supplements reduced participants’ systolic and diastolic blood pressure by 6 and 4 percent respectively.

In addition, anthocyanins can help prevent neurological disorders such as Parkinson’s and Alzheimer’s disease. They accomplish this by improving the communication between nerves and boosting blood flow to the brain. Their antioxidant effect also means they can stop brain damage caused by oxidative stress.

If you’re still not sold on the benefits of anthocyanins, consider this: They can fight cancer cells by attacking them and spurring cell death, in addition to activating the enzymes that rid your body of cancer-causing substances.

Studies have also shown that consuming foods rich in anthocyanins can lower your insulin resistance and protect beta cells in the pancreas, which helps normalize blood levels. That means anthocyanin-rich fruits can help inhibit diabetes.

Cardiovascular disease continues to be one of the top causes of death in America, affecting 84 million Americans and causing roughly one out of every three deaths. Those are very frightening statistics, so you owe it to yourself and your loved ones to consume more anthocyanins and take other steps known to reduce your risk, like exercising and eating as healthier diet overall.

People who drink moderate amounts of coffee each day have a lower risk of death from disease


Image: People who drink moderate amounts of coffee each day have a lower risk of death from disease

Many people drink coffee for an energy boost, but do you know that it can also prolong your life? A study published in the journal Circulation revealed that moderate amounts — or less than five cups — of coffee each day can lower your risk of death from many diseases, such as cardiovascular disease, Type 2 diabetes, and nervous system disorders. It can also lower death risk due to suicide.

The study’s researchers explained this effect could be attributed to coffee’s naturally occurring chemical compounds. These bioactive compounds reduce insulin resistance and systematic inflammation, which might be responsible for the association between coffee and mortality. (Related: Coffee drinkers have a lower mortality rate and lower risk of various cancers.)

The researchers reached this conclusion after analyzing the coffee consumption every four years of participants from three large studies: 74,890 women in the Nurses’ Health Study; 93,054 women in the Nurses’ Health Study 2; and 40,557 men in the Health Professionals Follow-up Study. They did this by using validated food questionnaires. During the follow-up period of up to 30 years, 19,524 women and 12,432 men died from different causes.

They found that people who often consumed coffee tend to smoke cigarettes and drink alcohol. To differentiate the effects of coffee from smoking, they carried out their analysis again among non-smokers. Through this, the protective benefits of coffee on deaths became even more apparent.

With these findings, the researchers suggested that regular intake of coffee could be included as part of a healthy, balanced diet. However, pregnant women and children should consider the potential high intake of caffeine from coffee or other drinks.

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Because the study was not designed to show a direct cause and effect relationship between coffee consumption and dying from illness, the researchers noted that the findings should be interpreted with caution. Still, this study contributes to the claim that moderate consumption of coffee offers health benefits.

The many benefits of coffee

Many studies have shown that drinking a cup of coffee provides health benefits. Here are some of them:

  • Coffee helps prevent diabetes: A study conducted by University of California, Los Angeles (UCLA) researchers showed that drinking coffee helps prevent Type 2 diabetes by increasing levels of the protein sex hormone-binding globulin (SHBG), which regulates hormones that influence the development of Type 2 diabetes. Researchers from Harvard School of Public Health (HSPH) also found that increased coffee intake may lower Type 2 diabetes risk.
  • Coffee protects against Parkinson’s disease: Studies have shown that consuming more coffee and caffeine may significantly lower the risk of Parkinson’s disease. It has also been reported that the caffeine content of coffee may help control movement in people with Parkinson’s disease.
  • Coffee keeps the liver healthy: Coffee has some protective effects on the liver. Studies have shown that regular intake of coffee can protect against liver diseases, such as primary sclerosing cholangitis (PSC) and cirrhosis of the liver, especially alcoholic cirrhosis. Drinking decaffeinated coffee also decreases liver enzyme levels. Research has also shown that coffee may help ward off cancer. A study by Italian researchers revealed that coffee intake cuts the risk of liver cancer by up to 40 percent. Moreover, some of the results indicate that drinking three cups of coffee a day may reduce liver cancer risk by more than 50 percent.
  • Coffee prevents heart disease: A study conducted by Beth Israel Deaconess Medical Center (BIDMC) and HSPC researchers showed that moderate coffee intake, or two European cups, each day prevents heart failure. Drinking four European cups a day can lower heart failure risk by 11 percent.

Rise of the Clones


Study identifies inherited and acquired mutations that drive precancerous blood condition

leukemia cells

Leukemia cells.

A new study led by researchers at Harvard Medical School and the Harvard T.H. Chan School of Public Health has identified some of the first known inherited genetic variants that significantly raise a person’s likelihood of developing clonal hematopoiesis, an age-related white blood cell condition linked with higher risk of certain blood cancers and cardiovascular disease.

The findings, published online July 11 in Nature, should help illuminate several questions about clonal hematopoiesis: how it arises, why it occurs in more than 10 percent of people over 65 and how the genome we inherit influences the mutations we acquire later in life.

The condition, uncovered in a series of studies over the past 10 years, is marked by the accumulation of genetically abnormal white blood cells, which may become cancerous or contribute to inflammation in atherosclerotic plaques.

“Clonal hematopoiesis is increasingly appreciated to be an important biomarker of risk for future illness, but we haven’t known what brings it about,” said the study’s co-senior author, Steven McCarroll, the Dorothy and Milton Flier Professor of Biomedical Science and Genetics at HMS and director of genetics at the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard.

“These findings reveal specific sequences of genetic events—some inherited, others acquired—that give rise to these abnormal blood cells,” he said.

The study also reaches the surprising conclusion that inherited genetic variants and acquired mutations are more connected than previously understood.

Acquired mutations are believed to occur randomly over time, appearing spontaneously or after exposure to damaging agents such as ultraviolet light. However, the team found examples where inherited variants led to the appearance of specific acquired mutations later in life or gave cells with such mutations a growth advantage over other cells.

“Conceptually one of the most intriguing things to come out of this work is the blurring of that distinction between genetic inheritance and acquired mutations,” said McCarroll. “Inherited alleles turn out to have powerful influences on what was previously thought to be a more capricious process.”

Out of proportion

Normally, each of the body’s 10,000 to 20,000 hematopoietic, or blood-forming, stem cells contributes roughly the same number of mature blood cells to the body’s total. The result: a pool of hundreds of billions of blood cells with many different parents.

Clonal hematopoiesis occurs when a single stem cell acquires mutations that cause it to produce far more than its share of new cells, including white blood cells. Over many years, the mutants out-compete normal blood cells, either proliferating more rapidly or surviving longer. Instead of the typical 1/10,000th, or 0.0001 percent, of a person’s total white cell count, the progeny of a single mutated stem cell might make up 2 percent, or 20 percent, or more than 90 percent of a person’s white blood cells. These genetically dominant blood cells are called clones.

Previous research from McCarroll’s lab and others showed that only some clones cause trouble. For example, only about 10 percent of people with clonal hematopoiesis go on to develop blood cancer. Even so, that risk is 10 times higher than that in the general U.S. population.

The team set out to learn which parts of the genome tend to be mutated in clones, which mutations are most harmful, and how clones arise and expand their numbers.

To do so, co-first authors Po-Ru Loh, assistant professor of medicine at HMS and Brigham and Women’s Hospital, and Giulio Genovese, senior computational biologist in the McCarroll lab, developed a mathematical approach that let them identify clones early on, when they accounted for as little as 1 percent of a person’s white blood cells. Previous methods lacked the precision to detect clones unless they had expanded to at least 15 to 20 percent of white blood cells.

Armed with their new technique, Loh and Genovese analyzed DNA from the blood of 151,000 people who’d donated samples to the UK Biobank.

Not so random after all

The increased level of sensitivity allowed the team to find clones in more than 8,000 participants, many of whom had acquired similar mutations.

To the researchers’ surprise, participants with similar acquired mutations often shared a rare, inherited variant nearby. Further investigation confirmed that this was far from a coincidence; the inherited variants had powerful effects on whether people acquired those other mutations later in life.

“When Giulio suggested searching for influences of inherited genetic variants, I never expected to turn up anything interesting,” said Loh. “When I first saw the results, the associations were so strong I wondered if they were a bug in the code.”

The researchers were then able to figure out the specific ways that the inherited variants made people vulnerable to developing clones.

The inherited variants and acquired mutations typically appeared in the same part of the genome. Some inherited variants made certain spots on chromosomes more vulnerable to future mutation. Others created easy ways for future mutations to increase the rate at which cells proliferate.

In some cases, an inherited variant inactivated one copy of a gene that normally protects against cancer. Later on, an acquired mutation inactivated the other copy.

“These are examples of what cancer geneticists call the two-hit model, where the inherited allele is the first hit and then the subsequent acquired mutation is the second hit,” said McCarroll. “It’s still not cancer, but having many, many white blood cells with that combination of mutations almost certainly puts one in a more vulnerable place.”

Another inherited variant inactivated one copy of a gene that promotes cell growth. This flummoxed the researchers at first, since the variant appeared to protect against aggressive cell growth or cancer. But many of the people who inherited this variant later acquired a mutation that replaced the inactivated gene with the full-strength copy inherited from the other parent. Cells with the acquired mutation then out-competed other cells.

The variants the team uncovered are rare, and inheriting one doesn’t guarantee that a person will develop clonal hematopoiesis. However, certain variants did make acquiring clones with a specific mutation much more likely—conferring up to a 50 percent chance, compared to the normal risk of well under 1 percent.

The researchers even found instances where multiple family members who inherited the same variant went on to develop clones with the same mutation.

The authors believe their findings are likely not a fluke.

“I think it’s safe to predict that these are early examples of a phenomenon we’ll see again and again,” said McCarroll.

The demographics of clones

Some acquired mutations were more common in women, others in men. Although clones in general are much more common in older people, two acquired mutations appeared across all ages, suggesting they arise from developmental rather than age-related processes.

The discoveries invite further efforts to understand the nature and consequences of each mutation.

“Although it’s been possible to say that, on average, clones might increase the risk of blood cancer tenfold, that doesn’t mean every specific clone does,” said McCarroll. “A key direction is to go from talking generically about clones to knowing each clone’s history and risk profile based on its specific mutations and frequency in the blood.”

As information builds, researchers will be able to better assess the risk of each clone and try to develop environmental or medical interventions might slow the growth of clones and avert disease, McCarroll said.

Omega-3 Level Is the Best Predictor of Mortality


Story at-a-glance

  • Omega-3 fats have once again been validated for their usefulness in predicting your risk for cardiovascular disease and all-cause mortality
  • Scientists suggest your omega-3 blood level actually is a better predictor of mortality than serum cholesterol
  • Omega-6 fats also have been linked to mortality, giving me another opportunity to remind you of the importance of balancing your intake of these two essential fatty acids
  • Nontoxic, wild fatty fish or a high-quality supplement are your best options for omega-3s; omega-6s are best obtained from eating nuts and seeds, not vegetable oils
  • I highly recommend you take the omega-3 index blood test to accurately determine and begin to track your omega-3 percentage; GrassrootsHealth offers a convenient, cost-effective test to measure both your vitamin D and omega-3 levels

By Dr. Mercola

Omega-3 has once again been validated for its usefulness to not only lower your risk of cardiovascular disease (CVD) but also your risk of all-cause mortality. Beyond that, the new research, funded by the National Institutes of Health, suggests measuring your omega-3 blood level may be a better predictor of your risk of death than your serum cholesterol.

Omega-6s also recently made the news for similar reasons, giving me an opportunity to remind you of the importance of balancing your intake of these two essential fatty acids. Because you are more likely to be omega-3 deficient, I highly recommend you take the omega-3 index blood test to accurately determine and begin to track your omega-3 percentage.

As part of a consumer-sponsored research project, GrassrootsHealth has created a convenient test kit to measure both your vitamin D and omega-3 index. This data will be used to analyze the health benefits of these vital nutrients, as well as any potential linkage between the two. Given the importance of vitamin D and omega-3s to your overall health and longevity, this is a test you simply cannot afford to overlook.

Omega-3 Level Slashes Your Risk of Mortality and CVD Events

Research funded by the National Institutes of Health once again highlights the importance of your omega-3 level to your heart health and overall well-being. The new study, published in the Journal of Clinical Lipidology,1 looked at the value of measuring blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 fatty acids to assess your risk for developing certain diseases. The outcome? A higher omega-3 index was associated with a lower risk for:

  • Total CVD events
  • Total coronary heart disease (CHD) events
  • Total strokes

In this body of work, led by omega-3 expert and prolific researcher William Harris, Ph.D., professor of medicine, Sanford School of Medicine, University of South Dakota, the omega-3 index was measured for 2,500 participants (54 percent women) in the offspring cohort of the Framingham Heart Study.2 The omega-3 index reflects the EPA and DHA content of your red blood cell membranes.

All participants, who had an average age of 66 years and were CVD free at baseline, were tracked until about age 73. Besides tracking total mortality, researchers also noted death from CVD, cancer and other causes, as well as any associations between omega-3 index levels and risk of CVD events, fatal or not.

While increased levels of omega-3s have been shown to reduce your CVD risk, the researchers also noted a strong association between the omega-3 index and death from all other causes. Notably, when comparing participant omega-3 index levels, those with the highest levels of omega-3 fatty acids slashed their risk of death from any cause by 34 percent.

This outcome suggests omega-3s provide other beneficial actions beyond the well-known ones associated with a pathological process, such as plaque buildup in your arteries, for example.3 The participants with the highest omega-3 index also had a 39 percent lower risk of suffering a CVD event such as a heart attack or stroke.

Even though the study was somewhat limited by its relatively short follow-up time (median 7.3 years), the researchers concluded: “A higher omega-3 index was associated with reduced risk of both CVD and all-cause mortality.”4

Move Over Serum Cholesterol: Omega-3 Is a Better Predictor of Mortality

While the mentioned results are noteworthy, the big news from Harris’ current study involved the comparing of omega-3 to serum cholesterol. Serum cholesterol level is defined as the total amount of cholesterol present in your blood and is still considered to be a risk factor for heart disease by conventional medicine even though this has been disproven.

Although earlier studies have affirmed the connection between higher omega-3 blood levels and a lower risk of death, Harris and his team compared omega-3 and serum cholesterol in hopes of determining which one is a better predictor of mortality. Omega-3 came out on top. About the findings, Harris said:5

“When baseline serum cholesterol levels were substituted for the omega-3 index in the same multivariable models, [serum cholesterol] was not significantly associated with any of the tracked outcomes, whereas the [omega-3 index] was related to four of the five outcomes assessed.”

What Is the Omega-3 Index and Why Is It Important?

Despite being aware of the importance of omega-3s, most people are unsure how much they need or if they are getting enough either through diet or a supplement. Generally speaking, omega-3 levels are low in much of Europe and the U.S. The Japanese, due to the amount of fish in their diet, tend to boast the highest levels globally. To help you find out and track your omega-3 level, Harris helped create the omega-3 index.

The omega-3 index is a blood test that measures the amount of EPA and DHA omega-3 fatty acids in your red blood cell (RBC) membranes. Your index is expressed as a percent of your total RBC fatty acids. The omega-3 index has been validated as a stable, long-term marker of your omega-3 status, and it reflects your tissue levels of EPA and DHA.

An omega-3 index over 8 percent — typical in Japan — is associated with the lowest risk of death from heart disease. An index below 4 percent, which is common in much of Europe and the U.S., puts you at the highest risk of heart disease-related mortality. Given its importance to your health, it is most definitely worth your time to complete the simple blood test required to determine your omega-3 index. I’ll share more about how to do that later in this article.

Studies Suggest Omega-6 Also Lowers Mortality Rates

A study published in The American Journal of Clinical Nutrition6 suggests omega-6 fatty acids may be equally beneficial in reducing your risk of premature death. Omega-6s, a group of polyunsaturated fatty acids, are found in nuts, seeds and vegetable oils. In drawing that conclusion, researchers from the University of Eastern Finland analyzed data from the Kuopio Ischaemic Heart Disease Risk Factor (KIHD).

The KIHD study is a large, ongoing study of cardiovascular risk that has followed about 2,500 middle-aged men living in eastern Finland where there are high recorded rates of coronary heart disease. The men, ages 42 to 60 at baseline, have been followed for an average of 22 years, during which their blood levels of fatty acids were tracked. More than 1,100 of the men have died from disease-related causes.

The omega-6 research team placed the KIHD men into five groups ranked according to their blood level of the omega-6 fat linoleic acid, after which they compared the rates of death in each group. Lead study author Jyrki Virtanen, Ph.D., adjunct professor of nutritional epidemiology at the University of Eastern Finland, and his team found that the group with the highest blood levels of linoleic acid had a 43 percent lower risk of death than the group with the lowest levels.

A more in-depth analysis revealed men with higher levels of linoleic acid were less likely to die from CVD or death by causes other than cardiovascular disease or cancer. No association was observed for death due to cancer. Said Virtanen, “We discovered that the higher the blood linoleic acid level, the smaller the risk of premature death.”7

Should You Consume More Omega-6?

The current Finland research supports findings from earlier population-based studies that have linked a higher dietary intake and higher blood level of linoleic acid to a reduced risk of CVD and Type 2 diabetes, without increasing cancer risk. For example, a 2014 systematic review and meta-analysis published in the journal Circulation8 analyzed 13 published and unpublished cohort studies involving 310,602 individuals and 12,479 total CHD events, including 5,882 CHD deaths.

Comparing the highest intake and lowest intake categories, researchers noted dietary linoleic acid was associated with a 15 percent lower risk of CHD events and a 21 percent lower risk of CHD deaths. Does this mean you should automatically reach for more omega-6s? The best sources for them, by the way, are from nuts and seeds, not vegetable oils.

The proposed health benefits of omega-6 fatty acids have been debated for quite some time. Like omega-3s, omega-6 fats are also essential and must come from your diet. While often praised for their effect on optimizing cholesterol levels, omega-6s are also thought to promote low-level inflammation, which is associated with cardiovascular disease.9 So, should you strive to eat more omega-6s? Probably not.

If you eat a Western diet, you very likely may be eating too few omega-3s, while consuming far too many omega-6s. The ideal ratio of omega-3 to omega-6 fats is 1-to-1, but the typical Western diet ranges between 1-to-20 and 1-to-50, depending on your eating habits. If a large portion of your diet centers around vegetable oil-laden fast food and processed foods, you are undoubtedly overdoing it on omega-6.

Processed foods — everything from french fries to frozen meals and salad dressings to snack foods — are generally loaded with omega-6s, due to the vegetable oils used to make them. Check labels carefully and do your best to avoid products containing canola, corn, cottonseed, safflower, soybean and sunflower oils. Furthermore, if you are a regular consumer of fast food, know that most of it is prepared with the same oils. Because these oils very often are damaged and oxidized, they are harmful for your body.

In general, when omega-6s predominate your diet, you will almost always suffer from inflammation. Omega-6 excess can also increase your production of body fat. Beyond that, many scientists suspect the high incidence of cancer, diabetes, heart disease, hypertension, obesity and premature aging experienced worldwide may have its roots in the chronic inflammation often triggered by this profound omega-3 to omega-6 mismatch.

In general, a diet high in omega-3 and low in omega-6 will reduce inflammation, while a diet low in omega-3 and high in omega-6 will promote inflammation. When your body is chronically inflamed, you will be unable to achieve optimal health.

The bottom line is that both omega-3s and omega-6s are essential to your diet. You cannot thrive without them. To clear up any lingering confusion, in the video above I provide helpful information about omega-3, omega-6 and omega-9 fatty acids. The main point is to strive for balance, choosing a mix of each type and taking care to ensure you incorporate high-quality animal sources for your omega-3s.

Your Best Source: Animal-Based Omega-3 Fats

Animal-based omega-3s are your best source for this essential fatty acid and you have the following three options to get more of it into your daily diet:

Fish: Small, cold-water, fatty fish such as anchovies and sardines are an excellent source of omega-3 with a low risk of hazardous contamination. Wild Alaskan salmon is another good source that is low in mercury and other environmental toxins.

Because much of the fish supply is heavily tainted with industrial toxins and pollutants, including heavy metals such as arsenic, cadmium, lead, mercury and radioactive poisons, it is extremely important to be selective, choosing fish high in healthy fats and low in contaminants.

Fish oil: While fish oil is a convenient and relatively inexpensive way to increase your intake of omega-3 fats, it typically delivers insufficient antioxidant support. Fish oil is perishable and oxidation leads to the formation of harmful free radicals. For this reason, you’ll need to increase your antioxidant protection when consuming fish oil to ensure it doesn’t oxidize and become rancid inside your body.

Krill oil: Krill oil is my preferred choice as an omega-3 supplement because it contains the indispensable animal-based DHA and EPA omega-3s your body needs in a form that’s less prone to oxidation. With the help of phospholipids, the nutrients in krill oil are carried directly to your cell membranes where they are more readily absorbed. Additionally, they can cross your blood-brain barrier to reach important brain structures. While you may be tempted to seek your omega-3 fatty acids from the following sources, mainly because they are readily available and perhaps less costly than the sources mentioned above, I strongly advise you to avoid:

Farmed salmon: It contains about half the omega-3 levels of wild salmon, is often fed a genetically engineered diet of corn and soy products and may contain antibiotics, pesticides and other chemical toxins

Large carnivorous fish: Marlin, swordfish and tuna (including canned tuna), for example, tend to contain some of the highest concentrations of mercury,10 a known neurotoxin

How To Clean Your Arteries With One Simple Fruit


How To Clean Your Arteries With One Simple Fruit

The future of cardiovascular disease prevention and treatment will not be found in your medicine cabinet, rather in your kitchen cupboard or in your back yard growing on a tree.

Pomegranate Found To Prevent Coronary Artery Disease Progression

A study published in the journal Atherosclerosis confirms that pomegranate extract may prevent and/or reverse the primary pathology associated with cardiac mortality: the progressive thickening of the coronary arteries caused by the accumulation of fatty materials known as atherosclerosis.[i]

Mice with a genetic susceptibility towards spontaneous coronary artery blockages were given pomegranate extract via their drinking water for two weeks, beginning at three weeks of age. Despite the fact that pomegranate treatment actually increased cholesterol levels associated with very low density lipoprotein-sized particles, the treatment both reduced the size of the atherosclerotic plaques in the aortic sinus (the dilated opening above the aortic valve) and reduced the proportion of coronary arteries with occlusive atherosclerotic plaques.

Remarkably, the researchers also found that pomegranate extract treatment resulted in the following 7 beneficial effects:

  1. Reduced levels of oxidative stress
  2. Reduced monocytie chemotactic protein-1, a chemical messenger (chemokine) associated with inflammatory processes within the arteries.
  3. Reduced lipid accumulation in the heart muscle
  4. Reduced macrophage infiltration in the heart muscle
  5. Reduced levels of monocyte chemotactic protein-1 and fibrosis in the myocardium
  6. Reduced cardiac enlargement
  7. Reduced ECG abnormalities

How can something as benign and commonplace as a fruit extract reverse so many aspects of coronary artery disease, simultaneously, as evidenced by the study above?  The answer may lie in the fact that our ancestors co-evolved with certain foods (fruits in particular) for so long that a lack of adequate quantities of these foods may directly result in deteriorating organ function.  Indeed, two-time Nobel Prize winner Linus Pauling argued that vitamin C deficiency is a fundamental cause of cardiovascular disease, owing to the fact that our hominid primate ancestors once had year-round access to fruits, and as a result lost the ability to synthesize it.

Pomegranate Found To Prevent Coronary Artery Disease Progression

There’s another obvious clue as to how pomegranate may work its artery opening magic. Anyone who has ever tasted pomegranate, or consumed the juice, knows it has a remarkable astringency, giving your mouth and gums that dry, puckering mouth feel. This cleansing sensation is technically caused, as with all astringents, by shrinking and disinfecting your mucous membranes.

Anyone who drinks pomegranate juice, or is lucky enough to eat one fresh, can understand why it is so effective at cleansing the circulatory system. Nature certainly planted enough poetic visual clues there for us: its juice looks like blood, and it does resemble a multi-chambered heart, at least when you consider its appearance in comparison to most other fruits.

Indeed, your mouth and your arteries are lined with the same cell type: epithelial cells. Together, they make up the epithelium, one of four basic tissue types within animals, along with connective tissue, muscle tissue and nervous tissue, and which comprises the interior walls of the entire circulatory system. So, when you feel that amazing cleansing effect in your mouth, this is in fact akin to what your circulatory system – and the epithelium/endothelium lining the inside of your veins and arteries – “feels” as well.

The Pomegranate “Artery Cleaning” Clinical Trial

Published in Clinical Nutrition in 2004 and titled, “Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation,” Israeli researchers discovered pomegranate, administered in juice form over the course of a year, reversed plaque accumulation in the carotid arteries of patients with severe, though symptomless, carotid artery stenosis (defined as 70–90% blockage in the internal carotid arteries).

The study consisted of nineteen patients, 5 women and 14 men, aged 65-75, non-smokers. They were randomized to receive either pomegranate juice or placebo. Ten patients were in the pomegranate juice treatment group and 9 patients that did not consume pomegranate juice were in the control group. Both groups were matched with similar blood lipid and glucose concentrations, blood pressure, and with similar medication regimens which consisted of blood-pressure lowering (e.g. ACE inhibitors, β-blockers, or calcium channel blockers) and lipid lowering drugs (e.g. statins).

The ten patients in the treatment group group received 8.11 ounces (240 ml) of pomegranate juice per day, for a period of 1 year, and five out of them agreed to continue for up to 3 years.

The remarkable results were reported as follows:

“The mean intima media thickness the left and right common carotid arteries in severe carotid artery stenosis patients that consumed pomegranate juice for up to 1 year was reduced after 3, 6, 9 and 12 months of pomegranate juice consumption by 13%, 22%, 26% and 35%, respectively, in comparison to baseline values.”

You can only imagine what would happen if a pharmaceutical drug was shown to reverse plaque build up in the carotid arteries by 13% in just 3 months! This drug would be lauded the life-saving miracle drug, and not only would be promoted and sold successfully as a multi-billion dollar blockbuster, but discussion would inevitably follow as to why it should be mandated.

While these results are impressive, if not altogether groundbreaking for the field of cardiology, they may be even better than revealed in the stated therapeutic outcomes above.  When one factors in that the carotid artery stenosis increased 9% within 1 year in the control group, the pomegranate intervention group may have seen even better results than indicated by the measured regression in intima media thickness alone.  That is, if we assume that the pomegranate group had received no treatment, the thickening of their carotid arteries would have continued to progress like the control group at a rate of 9% a year, i.e. 18% within 2 years, 27% within 3 years. This could be interpreted to mean that after 3 years of pomegranate treatment, for instance, the thickening of the arteries would have been reduced over 60% beyond what would have occurred had the natural progression of the disease been allowed to continue unabated.  

3 Ways How Pomegranate Heals The Cardiovascular System

The researchers identified three likely mechanisms of action behind pomegranate’s observed anti-atherosclerotic activity:

  • Antioxidant properties: Subjects receiving pomegranate saw significant reductions in oxidative stress, including decreases in autoantibodies formed against ox-LDL, a form of oxidized low density lipoprotein associated with the pathological process of atherosclerosis. Decreases in oxidative stress were measurable by an increase in the blood serum enzyme paraoxonase 1 (PON1) of up to 91% after 3 years; PON1 is an enzyme whose heightened activity is associated with lower oxidative stress. All of this is highly relevant to the question of pomegranate’s anti-atherosclerotic activity because of something called the lipid peroxidation hypothesis of atherosclerosis, which assumes that it is the quality of the blood lipids (i.e. whether they are oxidized/damaged or not), and not their quantity alone that determine their cardiotoxicity/atherogenicity. Essentially, pomegranate prevents the heart disease promoting effects of oxidative stress.
  • Blood Pressure Lowering Properties: The intervention resulted in significant improvement in blood pressure: the patient’s systolic blood pressure was reduced 7%, 11% ,10%, 10% and 12% after 1, 3, 6, 9, and 12 months of pomegranate consumption, respectively, compared to values obtained before treatment. Pomegranate’s ability to reduce systolic blood pressure indicates it has a healing effect on the endothelium, or the inner lining of the artery which fails to relax fully in heart disease; a condition known as endothelial dysfunction.
  • Plaque Lesion Stabilization: Because two of the ten patients on PJ (after 3 and 12 months) experienced clinical deterioration, carotid surgery was performed and the lesions were analyzed to determine the difference in their composition to those who did not receive pomegranate. The researchers noticed four distinct positive differences in the composition of the pomegranate-treated lesions: 1. Reduced Cholesterol Content: “The cholesterol content in carotid lesions from the two patients that consumed PJ was lower by 58% and 20%, respectively, in comparison to lesions obtained from CAS patients that did not consume PJ (Fig. 3A).” 2.     Reduced Lipid Peroxides: “[T]he lipid peroxides content in lesions obtained from the patients after PJ consumption for 3 or 12 months was significantly reduced by 61% or 44%, respectively, as compared to lesions from patients that did not consume PJ (Fig. 3B). 3.     Increased Reduced Glutathione Content: “A substantial increase in the lesion reduced glutathione (GSH) content, (GSH is a major cellular antioxidant) by 2.5-fold, was observed after PJ consumption for 3 or 12 months, (Fig. 3C). 4.     Reduced LDL Oxidation: “LDL oxidation by lesions derived from the patients after PJ consumption for 3 or 12 months, was significantly (Po0.01) decreased by 43% or 32%, respectively, in comparison to LDL oxidation rates obtained by lesions from CAS patients that did not consume PJ (Fig. 3D).”

Essentially these results reveal that not only does pomegranate reduce the lesion size in the carotid arteries, but “the lesion itself may be considered less atherogenic after PJ consumption, as its cholesterol and oxidized lipid content decreased, and since its ability to oxidize LDL was significantly reduced.”

This finding is quite revolutionary, as presently, the dangers of carotid artery stenosis are understood primarily through the lesion size and not by assessing for the quality of that lesion. This dovetails with the concept that the sheer quantity of lipoproteins (i.e. “cholesterol”) in the blood can not accurately reveal whether those lipoproteins are actually harmful (atherogenic); rather, if lipoproteins are oxidized (e.g. ox-LDL) they can be harmful (or representative of a more systemic bodily imbalance), whereas non-oxidized low density lipoprotein may be considered entirely benign, if not indispensable for cardiovascular and body wide health. Indeed, in this study the researchers found the pomegranate group had increased levels of triglycerides and very low density lipoprotein, again, underscoring that the anti-atherosclerotic properties likely have more to do with the improved quality of the physiological milieu within which all our lipoproteins operate than the number of them, in and of itself.

Finally, it should be pointed out that all the patients in this study were undergoing conventional, drug-based care for cardiovascular disease, e.g. cholesterol- and blood pressure-lowering agents. Not only did the pomegranate treatment not appear to interfere with their drugs, making it a suitable complementary/adjunct therapy for those on pharmaceuticals, but it should be pointed out that the control group’s condition got progressively worse (e.g. the mean IMT increased 9% within 1 year), speaking to just how ineffective drugs are, or how they may even contribute to the acceleration of the disease process itself.

Further Validation of Pomegranate’s Artery-Clearing Properties

Pomegranate’s value in cardiovascular health may be quiet broad, as evidenced by the following experimentally confirmed properties:

  • Anti-inflammatory: Like many chronic degenerative diseases, inflammation plays a significant role in cardiovascular disease pathogenesis. There are five studies on GreenMedInfo.com indicating pomegranate’s anti-inflammatory properties.[iii]
  • Blood-Pressure Lowering: Pomegranate juice has natural angiotensin converting enzyme inhibiting properties, [iv] and is a nitric oxide enhancer, two well-known pathways for reducing blood pressure. [v] Finally, pomegranate extract rich in punicalagin has been found reduce the adverse effects of perturbed stress on arterial segments exposed to disturbed flow.[vi]
  • Anti-Infective: Plaque buildup in the arteries often involves secondary viral and bacterial infection, including hepatitis C and Chlamydia pneumoniae.[vii] Pomegranate has a broad range of anti-bacterial and anti-viral properties.
  • Antioxidant: One of the ways in which blood lipids become heart disease-promoting (atherogenic) is through oxidation. LDL, for instance, may be technically ‘elevated’ but harmless as long as it does not readily oxidize. Pomegranate has been found to reduce the oxidative stress in the blood, as measured by serum paraoxonase levels.  One study in mice found this decrease in oxidative stress was associated with 44% reduction in the size of atherosclerotic lesions. [viii]
  • Ant-Infective: While it is commonly overlooked, cardiovascular disease, and more particularly atherosclerosis, is connected to infection. Dentists know this, which is why they often prescribe antibiotics following dental work which releases bacteria into systemic circulation. Plaque in the arteries can also harbor viral pathogens. Pomegranate happens to have potent antiviral and antibacterial properties relevant to cardiovascular disease initiation and progression. It has been studied to combat the following infectious organisms:
    1. Avian Influenza
    2. Candida
    3. Escherichia Coli
    4. Hepatitis B
    5. HIV
    6. Influenza A
    7. Poxviruses
    8. Salmonella
    9. SARS
    10. Staphylococcus auerus
    11. Vaccinia virus
    12. Vibrio (Cholera) virus

For additional research on pomegranate’s heart friendly properties read our article: Research: Pomegranate May Reverse Blocked Arteries, and to learn more about it’s broadly therapeutic properties read: 100+ Health Properties of Pomegranate Now Includes Helping Diabetics.

Also, view our dedicated research section on reversing arterial plaque: Clogged Arteries


Resources

AHA Addresses Heart Effects of Breast Cancer Tx


Breast cancer patients and survivors may have a heightened risk of cardiovascular disease (CVD) and require careful monitoring, particularly when treatment includes drugs that can damage the heart, according to a scientific statement from the American Heart Association (AHA).

Breast cancer patients, particularly older patients, are more likely to die of CVD than breast cancer, and patients may benefit from management strategies that weigh the cancer benefits versus heart risks, authors of the statement wrote in Circulation.

“Any patient who is going to undergo breast cancer treatment, whether they have heart disease at the beginning or not, should be aware of the potential effects of the treatment on their heart,” writing group chair Laxmi Mehta, MD, said in a statement. “This should not deter or scare patients from undergoing breast cancer treatment but should allow them to make informed decisions with their doctor on the best cancer treatment for them.”

The association between breast cancer and CVD begins with overlapping risk factors, including older age, obesity, and smoking. As much as 80% of attributable risk for CVD can be eliminated by attention to modifiable risk factors, including a healthy diet, abstinence from tobacco, maintenance of a healthy weight, blood pressure control, a favorable lipid profile, diabetes management, and physical activity. Some evidence suggests that following the AHA Life’s Simple 7 lifestyle-based health campaign may help lower the risk of cancer.

The evidence regarding postmenopausal hormone replacement therapy (HRT) is mixed. Data from the Nurses Health Study showed an increased risk of breast cancer in women taking HRT. In contrast, data from the Women’s Health Initiative suggested the effect varied according to the type of hormones used and whether a woman had an intact uterus. Several studies have found positive associations between HRT and CVD in older postmenopausal women and women with existing coronary disease.

Authors of the AHA statement concluded, “These data confirm that postmenopausal HRT is associated with both breast cancer and CVD … and this is a potentially modifiable risk factor for both diseases.”

With regard to potential adverse effects of cancer treatment on the heart, the AHA panel noted that two widely used cancer medications — doxorubicin and trastuzumab (Herceptin) — can damage heart tissue and reduce the heart’s functional capacity, effects associated with the development of heart failure.

The anthracycline class of chemotherapeutic drugs can trigger abnormal heart rhythms, which may be benign or potentially life-threatening. Antimetabolites can cause vasospasm that produces symptoms ranging from chest pain to heart attack.

Among options for hormonal breast cancer therapy, tamoxifen favorably affects lipid profiles, but studies showed no beneficial effect on CVD risk. Tamoxifen adversely affects clotting parameters and increases the risk of venous thrombosis and thromboembolism. Aromatase inhibitors (AI) are associated with a lower risk of clot-related disorders as compared with tamoxifen. Pooled data and meta-analyses suggested that AI use modestly but significantly increases the risk of CVD versus tamoxifen.

“Despite the small absolute risk, the clinical relevance of these findings could be high in specific populations at risk,” the AHA panel concluded.

Radiation therapy can affect blood vessels in ways that make patients more likely to develop coronary artery disease. Despite improvements in technology and delivery techniques, “irradiation to smaller volumes of the heart results in cardiac perfusion defects,” the AHA panel stated.

Certain clinical management strategies may help reduce or prevent the adverse effects of breast cancer therapy. For example, some studies suggested that administration of doxorubicin by slow infusion rather than bolus may minimize damage to the heart. Additionally, the drug dexrazoxane is approved for minimizing heart damage in patients with metastatic breast cancer treated with high doses of doxorubicin.

 Heart health should figure into the initial planning of breast cancer treatment, including drug choices and follow-up monitoring during treatment, said Mehta. In some cases, pre-existing heart conditions may guide the course of cancer care, or cancer therapy may adversely affect the heart and necessitate changes in treatment plans.

“Ideal breast cancer outcomes are reliant on coexisting cardiovascular health along the entire journey of breast cancer treatment,” the AHA panel concluded.

Early Menarche, Menopause Tied to Higher CVD Risk


Several reproductive factors contributed to a higher risk of cardiovascular disease among women, including early periods and early menopause, researchers found.

A history of hysterectomy was also linked with increased risk of cardiovascular disease (CVD) and coronary heart disease, reported Sanne AE Peters, PhD, and Mark Woodward, PhD, both of the University of Oxford in England.

However, history of oophorectomy, as well as age at first birth, had either no associations or only minor inverse associations with increased risk for cardiovascular disease, the authors wrote in Heart.

They pointed to “increasing evidence” that in addition to traditional risk factors such as elevated blood pressure, smoking, and obesity, certain reproductive factorsmay be linked with later cardiovascular disease, though the evidence is “mixed and inconsistent.”

This cross-sectional analysis of UK Biobank data comprised 267,440 women and 215,088 men ages 40 to 69 without a history of cardiovascular disease. The authors found that during 7 years of follow-up, there were 9,054 cases of cardiovascular disease, 5,782 cases of coronary heart disease, and 3,489 cases of stroke. Women comprised about a third of cardiovascular disease cases, a little under 30% of coronary heart disease cases, and about 40% of stroke cases.

Examining demographic data for women, the mean age was 56, about half were from a higher socioeconomic bracket in the U.K., and 60% said they never smoked.

Results were mixed for certain reproductive factors and increased risk for cardiovascular disease. The mean age for menarche was 13 years, and women who had their first periods prior to age 12 had a higher risk of cardiovascular disease (adjusted HR 1.10, 95% CI 1.01-1.30) than women who had menarche at a later age. Similar increased risks were seen for coronary heart disease (adjusted HR 1.05, 95% CI 0.93-1.18) and stroke (adjusted HR 1.17, 95% CI 1.03-1.32).

 Sixty-one percent of women in the study were postmenopausal, with a mean age at natural menopause of 50 years. But early menopause was also linked with increased risk of cardiovascular disease (adjusted HR 1.33, 95% CI 1.19-1.49), coronary heart disease (adjusted HR 1.29, 95% CI 1.10-1.51), and stroke (adjusted HR 1.42, 95% CI 1.21-1.66).

Likewise, history of hysterectomy was linked with an increased risk of cardiovascular disease (adjusted HR 1.12, 95% CI 1.03-1.22) and coronary heart disease (adjusted HR 1.20, 95% CI 1.07-1.34).

Eighty-five percent of women had been pregnant, and 44% of women had two children, while 42% of men had fathered two children. Compared with women and men without children, there was a significantly higher risk of coronary heart disease in women (adjusted HR 1.21, 95% CI 1.05-1.40). But because these risks were similar among men (adjusted HR 1.13, 95% CI 1.04-1.23), the authors concluded that “this is unlikely to be due to a biological cause.”

The authors suggested that, “More frequent cardiovascular screening would seem to be sensible among women who are early in their reproductive cycle, or who have a history of adverse reproductive events or a hysterectomy, as this might help to delay or prevent their onset of CVD.”

Brush Your Teeth To Save Your Heart: Oral Infections Increase Inflammation In Cardiovascular Disease


Dental care

Dental careMaintaining good oral hygiene is key to preventing heart disease, stroke, and other chronic illnesses.

It’s well established that keeping your teeth clean and your gums healthy not only benefits your smile, but has a huge impact on your overall health. Now, a new study published in Trends in Endocrinology and Metabolism reminds us of the importance of oral health — particularly when it comes to heart disease.

The authors of the study found that oral infections and mouth bacteria can increase your risk of cardiovascular disease and inflammation. Oral infections like cavities and periodontal diseases (gingivitis, periodontitis) are the most common diseases among humans, and they are all chronic inflammatory diseases. Past research has highlighted the link between poor oral health and increased risk of cardiovascular disease, and it has also been associated with a higher risk of stroke, especially among men.

Oral infections often allow bacteria to travel through the bloodstream to the heart and arteries, increasing cholesterol and triggering inflammation.

“Given the high prevalence of oral infections, any risk they contribute to future cardiovascular disease is important to public health,” Thomas Van Dyke of the Forsyth Institute, an author of the study, said in the press release. “Unraveling the role of the oral microbiome and inflammation in cardiovascular disease will likely lead to new preventive and treatment approaches.”

The authors of the study tried to examine the best therapeutic avenues to treat both periodontitis, which is inflammatory, and cardiovascular disease. They found that a high dose of a cholesterol-lowering medicine known as atorvastatin, which increases the anti-inflammatory molecules lipoxins and resolvins in the blood, was effective at controlling both periodontal and cardiovascular inflammation.

“New discoveries of natural pathways that resolve inflammation have offered many opportunities for revealing insights into disease pathogenesis and for developing new pharmacologic targets for the treatment of both oral infections and cardiovascular disease,” Van Dyke said in the press release.

It’s often easy to see your teeth and mouth as separate of sorts from the rest of your body, but the reality is that they are intimately linked. As Dr. Kesavalu Lakshmyya, an author of a study on periodonotitis and heart disease, told The Telegraph. “The mouth is the gateway to the body.”

Periodontitis is a gum infection that destroys the soft tissue as well as the bone that supports your teeth. It can become serious if left untreated and may ultimately lead to tooth loss, but the funny thing is that it’s incredibly easy to prevent; it’s usually the result of poor oral hygiene. So if you needed a better reason to start brushing your teeth with more dedication, this is it.

“The majority of diseases and conditions of aging, including obesity and type 2 diabetes, have a major inflammatory component that can be made worse by the presence of periodontitis,” Van Dyke said. “Periodontitis is not just a dental disease, and it should not be ignored, as it is a modifiable risk factor.”

Source: Kholy K, Genco R, Van Dyke T. Oral infections and cardiovascular disease. Trends in Endocrinology and Metabolism. 2015.

Diabetes, cardiovascular disease, and chronic kidney disease in South Asia: current status and future directions


South Asians are more susceptible to diabetes and cardiovascular diseases and have worse outcomes than other ethnicities, say Anoop Misra, Tazeen Jafar, and colleagues. They call for urgent action to provide screening and treatment, complemented by population level lifestyle modifications.

All South Asian countries have adopted the World Health Organization’s Global Action Plan for the Prevention and Control of Non-Communicable Diseases, which recommends a 25% relative reduction in the prevalence of raised blood pressure by 2025 and a halt to the rise in diabetes and obesity. Although considerable diversity exists between countries, all South Asians have markedly elevated risks of diabetes and variably elevated risks of cardiovascular disease compared with other ethnicities.12 In this paper, we review the burden of diabetes, cardiovascular disease, and chronic kidney disease in the region and policies to mitigate this burden. We identify key actions for health authorities and governments to attenuate the rise in non-communicable diseases and meaningfully improve outcomes for the millions of people with, or expected to develop, these diseases.

Methods

We gathered data on characteristics of populations and health systems from publicly available World Bank reports and WHO’s country profiles. Information on death and disability from cardiovascular disease, diabetes, and chronic kidney disease and their attributable risk factors came from Health Metrics and Evaluation’s data visualisation tool of the Global Burden of Disease Study 2015. We searched PubMed and Google scholar for relevant literature up to January 2017, using the terms “South Asians”, “diabetes”, “cardiovascular disease”, “myocardial infarction”, “stroke”, “renal”, and “kidney disease”. We formulated this paper by drawing from our collective experience in this field and the available literature.

Current epidemiology and trends

Cardiovascular disease, diabetes, and chronic kidney disease now account for 27%, 4.0%, and 3.0% of deaths, respectively, in South Asia (table 1).3456 Notwithstanding the limited quality and breadth of data, ischaemic heart disease is the leading cause of death in India, Pakistan, Nepal, and Sri Lanka, and stroke is the leading cause in Bangladesh.

The age standardised years of life lost as a result of cardiovascular disease has increased in South Asia in contrast to most other regions, where the reverse is true.5 In part, this is because cardiovascular disease events are more common in South Asia than in high income countries.78 Furthermore, acute myocardial infarction occurs six years earlier in South Asians than in European counterparts, probably owing to earlier onset of risk factors. Case fatality rates are higher in South Asia, especially in younger adults, thereby increasing the years of life lost.78 Stroke and chronic kidney disease may also occur earlier in South Asians.91011 The effect of lives lost due to premature cardiovascular disease is far worse in South Asia than elsewhere, as more than half of the population lives in conditions of poverty.3

Susceptibility to diabetes, cardiovascular diseases, and chronic kidney disease

The region has experienced rapid demographic, epidemiological, environmental, and economic transitions. These, coupled with unhealthy lifestyles of physical inactivity and consumption of a calorie dense diet, have increased the risk of non-communicable diseases. In addition, social disparities, wealth inequalities, and conflicts in the region contribute to high rates of stress associated behaviours including smoking.1112 Evidence from multi-country case-control studies indicates that hypertension, dyslipidaemia, smoking, obesity, diabetes, physical inactivity, low fruit and vegetable intake, and psychosocial stress attribute up to 90% of the population risk of cardiovascular disease in South Asians.1314 Age standardised blood pressure and cholesterol levels and prevalence of diabetes have increased in South Asia over the past decades.151617 High blood pressure and high blood glucose are the leading attributable risk factors for deaths from chronic kidney disease in every South Asian country (table 2).

Adverse metabolic factors are evident in South Asians at an early age. South Asian children have been shown to have adverse metabolic factors (hyperinsulinaemia, dyslipidaemia) compared with British children of similar age and body mass index and higher blood pressure than white children in the US.1819 Physical inactivity, dietary imbalances, and increasing obesity amplify this (fig 1).2021

 

Fig 1 Interacting risk pathways contributing to higher risks of diabetes and cardiovascular disease (CVD) in South Asians, acting over the life course. This begins with poor maternal nutrition and adverse programming, with neonates born at lower average birth weights yet higher fat to lean mass ratios compared with white children. This phenotype worsens over time, with greater weight gain and lower activity levels in South Asian children and adults, leading, in turn, via greater insulin resistance and CVD risk factors, to higher rates of diabetes and CVD, respectively. The parallel societal, political, and health considerations, as well as life course considerations, are also shown. BMI=body mass index; BP=blood pressure; CKD=chronic kidney disease

“>Figure1

Fig 1

 Interacting risk pathways contributing to higher risks of diabetes and cardiovascular disease (CVD) in South Asians, acting over the life course. This begins with poor maternal nutrition and adverse programming, with neonates born at lower average birth weights yet higher fat to lean mass ratios compared with white children. This phenotype worsens over time, with greater weight gain and lower activity levels in South Asian children and adults, leading, in turn, via greater insulin resistance and CVD risk factors, to higher rates of diabetes and CVD, respectively. The parallel societal, political, and health considerations, as well as life course considerations, are also shown. BMI=body mass index; BP=blood pressure; CKD=chronic kidney disease

 South Asian adults have greater risks of cardiovascular disease and diabetes, both of which tend to manifest around 5-10 years earlier than in white Europeans.10 The risk of cardiovascular disease is independent of that predicted by established risk factors. Possible mechanisms, among others, include an atherogenic dyslipidaemia driven by high concentrations of triglycerides and low concentrations of high density lipoprotein cholesterol, a pro-coagulant tendency, and higher concentrations of inflammatory cytokines.22 Further work is needed to define mechanisms for this excess cardiovascular disease risk. The risk factors vary by socioeconomic strata, geographical region, and migration.

Of particular importance, South Asian adults are more insulin resistant at any given body mass index and may experience more rapid β cell failure.2 They may progress more rapidly from a state of high risk of diabetes to frank diabetes and may have accelerated microvascular damage, with evidence of earlier diabetic nephropathy and retinopathy.2

Effects of poor and inconsistent treatment

Significant treatment gaps exist in South Asian populations. Studies report that less than half of all people with hypertension have received a diagnosis or treatment and less than a third have their blood pressure controlled with drugs.232425 The rates of diabetes awareness (50%), glycaemic control (<30%), and chronic kidney disease awareness (<15%) are suboptimal.24262728

Delay or prevention of diabetes in South Asians will require earlier intervention—that is, at lower levels of glycaemia. This requires wider testing and earlier use of antihyperglycaemic treatment, complemented with population-wide strategies to drive change in dietary habits and physical activity. Although antihypertensive, antidiabetic, and lipid lowering drugs are part of WHO’s list of essential medicines, availability in government primary care facilities is poor and patients must often pay out of pocket for these drugs. Social insurance schemes in countries are not available to the majority of the population,2930 and they tend to cover hospital based treatment and do not provide for standardised screening and medical management of these conditions in primary care.

Under-diagnosis and under-treatment result in higher rates of myocardial infarction and stroke, with adverse outcomes due to poor access to standardised and affordable treatment. Most patients with acute ischaemic heart disease are brought to the hospital too late to qualify for reperfusion therapy.31 Management in primary care is less than satisfactory, and many patients do not receive appropriate drugs owing to gaps in the knowledge and practices of healthcare providers.323334 The situation is much worse in rural areas, where an acute event is more likely to be fatal.3135

Health policies are not geared to respond to the rising challenge

Non-communicable diseases have been a recent addition to the policy agenda in all South Asian countries. Public health expenditure varies across countries, but overall investment is insufficient to support services for the prevention and management of cardiovascular disease, diabetes, and chronic kidney disease (table 3).36Implementation has been slow owing to donor agencies having limited interest in investing in non-communicable diseases and lack of engagement between governments and professional organisations in this field.

Table 3

Characteristics of health systems and policies for management of cardiovascular diseases and diabetes in South Asia

 In India, the National Programme for Prevention and Control of Cancer, Diabetes, CVD and Stroke has piloted opportunistic screening of risk factors for non-communicable diseases for people over 30 years of age. Furthermore, as part of the national health mission, the Indian government has outlined an operational plan for universal screening for hypertension and diabetes.31 A model of opportunistic screening for diabetes in patients with tuberculosis is being evaluated in Sri Lanka.37 Examples of successful public-private partnerships for non-communicable disease healthcare in the region are limited. Pakistan’s National Action Plan for Non-communicable Diseases is one such model,38 which involved a tripartite collaboration with Heartfile, a not for profit organisation, in formulation of policy and implementation in partnership with the government and WHO.

Recommendations

Progress towards the targeted reductions in death and disability from cardiovascular disease, diabetes, and chronic kidney disease would not be possible without concerted, multi-sectoral efforts by various government entities and non-government partners. We recommend the following essential policy and health system interventions.

Implementation of taxes on unhealthy foods

A tax of 20% on sugar sweetened drinks in India is projected to reduce the prevalence of overweight and obesity by 3.0% (95% confidence interval 1.6% to 5.9%) and the incidence of type 2 diabetes by 1.6% (1.2% to 1.9%) over the period 2014-23, assuming that consumption increases in line with current trends.39 In Mexico, an excise tax of 10% on sugar sweetened drinks decreased consumption by an average of 6% over one year.40 The Indian state of Kerala recently announced a “fat tax” on pizzas, burgers, sandwiches, and tacos sold through branded food outlets.41 Such strategies must be adopted in cities of South Asia that experience widespread marketing and consumption of unhealthy fast foods.

Furthermore, a 20% tax on palm oil purchases in India is projected to avert approximately 363 000 (95% confidence interval 247 000 to 479 000) deaths from myocardial infarctions and strokes over the period 2014-23 (1.3% reduction in cardiovascular deaths).42 Palm oil is consumed widely in low and middle income countries. It is high in saturated fat and causes a large increase in cholesterol concentrations. Empirical data from Mauritius show a reduction of 1 mmol/L in cholesterol concentrations through substitution of palm oil with soya oil.43 This reduction in cholesterol and low density lipoprotein cholesterol would equate to a 22% lower risk for cardiovascular disease, a huge effect by any standards.44

Strengthening of health system capacity to deliver care for non-communicable diseases

Strengthening of health systems and a well designed quality of care improvement framework are essential for concerted efforts to manage hypertension and diabetes for prevention of cardiovascular disease and chronic kidney disease. Shifting management of chronic diseases and risk factors from doctors to community healthcare workers holds promise and is being tested in rural areas in South Asia.34 Studies from Pakistan and India have shown that involving trained health workers in home health education on diet and physical activity and training general practitioners led to earlier diagnosis and better management of patients with hypertension or diabetes, and it was also cost effective.454647 Scaling up similar models is likely to offer substantial reductions in cardiovascular disease and chronic kidney disease in the medium to long term.

Screening populations at high risk (such as people who are sedentary, overweight, or smokers; those with hypertension; those with a family history of diabetes or premature cardiovascular disease in first degree relatives; and women with a history of gestational diabetes) is essential for early diagnosis. Low cost strategies such as validated simple screening questionnaires, blood pressure measurement, and, if possible, fasting or random blood glucose measurement, urinary dipstick for protein, and non-fasting cholesterol measurement, may be used. Although the cost effectiveness of opportunistic screening compared with universal screening is likely to vary according to the characteristics of the population, its value cannot be overstated for countries with a high prevalence of diabetes.48

Making antihypertensives, statins, and diabetes drugs available for free or at low cost in primary healthcare centres should be prioritised. This is consistent with achievement of universal health coverage, including access to quality and affordable essential medicines for all, as advocated in the United Nations’ sustainable development goals.49High quality generic drugs produced in the region can help to make this sustainable. Fixed dose drug combinations may improve coverage and long term adherence in people with established disease, but their widespread use in primary prevention is still debated.50 Health insurance reforms must provide for screening and primary care for these conditions to reduce out of pocket expenditure.51

Evidence is growing for m-health (mobile health technologies) interventions in improving adherence to treatment, maintaining appointments, data collection, and supporting health workers.52 More than 80% of the population of South Asia have mobile phones, and a large majority of villages are connected with mobile technology.53 This platform should be strongly considered in risk communication strategies and integration of care delivery for non-communicable diseases where feasible.

Public-private partnerships for non-communicable disease care should be encouraged to provide for unmet needs. Setting standards for long term public sector engagement; having transparent goals, inputs, and expectations; good governance of costs and fair allocation of profits; a shared vision and trust; and agreed processes for negotiation on common interests of partners are crucial to their success. The Sindh Institute of Urology and Transplantation in Karachi, Pakistan, providing dialysis services, and Aravind Eye Care System in India are good examples of successful public-private partnerships in the region.5455

Consideration of population based strategies to promote a healthy lifestyle

Community based interventions to promote a healthy diet and physical activity and reduce smoking and stress will go a long way in delaying the onset of these diseases. The Indian Diabetes Prevention Program, and more recently the D-CLIP study, showed the effectiveness of lifestyle intervention in reducing the development of diabetes in people at high risk, while concurrently tackling problems with community acceptability and long term sustainability.5657

School health programmes, encouraged by WHO to inform children about risk factors for non-communicable diseases and promote physical activity, have been hindered by low education budgets and poor infrastructure. There are no restrictions on advertising unhealthy food to minors.58 Such legislation must be complemented with multi-sectoral action including involvement of schools and workplaces to influence diet and physical activity.

Investment in surveillance and research

Surveillance and monitoring are critical to raise awareness and inform policy and implementation. Although the WHO STEPS instrument (www.who.int/chp/steps/instrument/en/) for collecting data on risk factors for non-communicable diseases has been used in community based studies in South Asia, national implementation is lacking.59 All South Asian countries must institutionalise risk factor surveillance and establish robust cardiovascular disease, diabetes, and chronic kidney disease registries to track trends and monitor progress. Surveillance data must be shared publicly to create awareness.

Evidence on effective interventions to prevent and control non-communicable diseases in the region is very limited. The effect of school, workplace, and community based interventions must be evaluated. Research comparing single versus multiple risk factor screening, as well as opportunistic and targeted screening versus universal screening in all adults, will help to tailor screening strategies. Policy initiatives such as taxes and diet substitution must be rigorously evaluated for their feasibility and impact at a population level.

Conclusion

Capacity building, financing, and a strong quality assurance framework are crucial for the effectiveness, scalability, and long term sustainability of initiatives to curb non-communicable diseases in the South Asia region.

Key messages

  • South Asians are more likely than other ethnicities to develop diabetes, cardiovascular disease, and chronic kidney disease, and these often have an earlier onset and poor outcomes

  • Strategies for early diagnosis and treatment including awareness generation, opportunistic screening, availability of low cost drugs, and task shifting to health workers must be prioritised

  • Countries must consider taxation on unhealthy foods, restrictions on advertising, and appropriate food labelling.

source: BMJ