SITAGLAPTIN USE AND HEART FAILURE RISK

Signals of a possible heart-failure (HF) hazard from second-line treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes seen in recent randomized and observational studies have risen a few decibels^[1]. An analysis of patient-level data from nationwide US insurance records saw initiation of sitagliptin (Januvia, Merck), one the most commonly used DPP-4 inhibitors, pose an 84% increased risk (p=0.01) of new HF hospitalization among diabetic patients initially with HF who had been treated withmetformin or a sulfonylurea. The more than 7600 patients in the cohort had been followed a median of 1.4 years.

Sitagliptin therapy showed no sign of increasing risk for all-cause hospitalization or death, which was the primary end point of the study, published July 2, 2014 in Circulation: Heart Failureby first author Daniala L Weir (University of Alberta, Edmonton) and colleagues.

As in prior analyses hinting at similar risks from DPP-4 inhibitors, in which only some diabetic patients already had HF when the drugs were started, HF hospitalization was a secondary end point while primary-end=point outcomes for DPP-4 inhibition were, in contrast, often favorable or neutral.

The increased HF risk in the current analysis "is likely clinically relevant," according to the authors, with an observed number needed to harm of 29, "and may have implications for choice of add-on therapy for patients with HF and diabetes poorly controlled with other agents."

They continue, "Although our results are intriguing, it is clear that additional studies are required, specifically in patients with HF, to solidify the risk/benefit picture," especially given "inconsistent" evidence from clinical trials regarding any HF risk from DPP-4 inhibitors.

Recent Causes for Concern

The randomized SAVOR-TIMI 53 trial of saxagliptin (Onglyza, Bristol-Myers Squibb/AstraZeneca) showed a significant 27% increased risk of HF hospitalization in 16 492 diabetic patients with a CV history or otherwise at elevated CV risk. That was despite saxagliptin noninferiority for the primary end point of CV death, nonfatal MI, or nonfatal ischemic stroke vs placebo.

And the 5380-patient Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE) trial ofalogliptin (Nesina, Takeda Pharmaceuticals) showed a nonsignificant trend suggesting more HF in diabetic patients taking the DPP-4 inhibitor. Both studies had been reported by heartwire .

On the other hand, a recent unpublished post hoc analysis of the much smaller Vildagliptin in Ventricular Dysfunction Diabetes Trial (VIVIDD), which focused on echocardiographic rather than clinical end points, found no elevated risk of HF hospitalizations or other HF events in diabetic patients with HF who received vildagliptin (Galvus, Novartis).

Two observational studies presented recently at the International Society of Endocrinology and the Endocrine Society joint scientific sessions, and covered by Medscape Medical News, gave somewhat conflicting results regarding DPP-4-inhibitor use and HF outcomes. One retrospective study of 13 185 outpatients with diabetes on metformin showed a significantly elevated HF risk over four years among those also taking a DPP-4 inhibitor compared with a different second-tier antidiabetic agent. And in the other study, a cohort of 32 419 matched pairs of patients with diabetes taking or not taking a DPP-4 inhibitor, DPP-4 inhibitors were not associated with an increased risk of CV events and may have even improved HF overall.Data from Diabetic Patients Initially With HF

The analysis of 7620 diabetic patients and HF (58% male) treated with metformin or a sulfonylurea but not a thiazolidinedione included 887 patients who started on sitagliptin sometime after their HF diagnosis.

In an adjusted analysis, there were no differences between sitagliptin users and nonusers for the primary end point of all-cause hospitalization or death, the secondary end point of HF hospitalization or death from any cause, or all-cause death or all-cause hospitalization by themselves. However, HF admissions went up significantly with sitagliptin.

In addition, treatment with metformin was associated with a 22% reduced adjusted risk of the primary end point (p<0 .001="" 10="" 16="" and="" end="" for="" insulin="" of="" p="0.004).</p" point="" raised="" sulfonylureas="" that="" users="" was="" whereas="">

"Before recent studies, there was little evidence, either clinical or basic science, to suggest DPP-4 inhibition would increase the risk of heart failure," write Drs Deepak L Bhatt and Matthew A Cavender (Brigham and Women's Hospital, Boston, MA) in an accompanying editorial^[2].

"In contrast, basic science data largely suggested that DPP-4 inhibition should improve cardiovascular events, including ventricular function," they continue, noting the confusing state of the evidence so far.

"The findings of this analysis, as well as other recent studies, highlight the need for well-designed trials that rigorously assess for HF in patients with diabetes. The ongoing . . .  Trial Evaluating Cardiovascular Outcomes with Sitagliptin [TECOS] has randomized approximately 14 000 patients with type 2 diabetes [and preexisting CVD] to sitagliptin or placebo, and it may help establish whether the class of DPP-4 inhibitors does indeed cause HF."

Adjusted* Odds Ratio (95% CI), Exposure vs No Exposure to Sitagliptin and Metformin in Diabetic Patients With HF

End points	Sitagliptin OR (95% CI), p	Metformin OR (95% CI), p
All-cause death or hospitalization	0.84 (0.69–1.03), 0.10	0.78 (0.71–0.85), <0 .001="" td="">
All-cause death	1.16 (0.68–1.97), 0.59	0.52 (0.37–0.71), <0 .001="" td="">
All-cause hospitalization	0.93 (0.76–1.14), 0.46	0.79 (0.71–0.87), <0 .001="" td="">
HF-related hospitalization or death	1.34 (0.93–1.92), 0.12	0.70 (0.57–0.86), 0.001
HF-related hospitalization	1.84 (1.16–2.92), 0.01	0.87 (0.66–1.12), 0.28

*Adjusted for age and sex; type of medical insurance; household income; recent glycosylated hemoglobin, low- and high-density lipoprotein cholesterol, triglycerides, and estimated glomerular filtration rate; history of CVD; antidiabetic drug therapies; CV drug therapies

CI=confidence interval

OR=odds ratio

The trial's primary end point is "time to first confirmed CV event (a composite defined as CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization)." Time to congestive HF is a TECOS secondary end point.

According to Weir et al, although the ongoing DPP-4 inhibitor trial as well as the earlier ones "enrolled patients with established cardiovascular disease or risk factors, none specifically identified individuals with established heart failure. Therefore, it is unlikely the upcoming results of the TECOS trial will provide evidence for the safety of sitagliptin therapy in those with preexisting HF, unless evaluated as a subgroup."

GENOMICS OF LUNG CANCER

Researchers from Dana-Farber Cancer Institute, the Broad Institute of MIT and Harvard, and other centers have identified novel mutations in a well-known cancer-causing pathway in lung adenocarcinoma, the most common subtype of lung cancer. Knowledge of these mutations could potentially identify a greater number of patients with treatable mutations because many potent cancer drugs that target these mutations already exist. In addition, these findings, published online in Nature, may expand the number of possible new therapeutic targets for this disease.

Study Details

In this new study researchers from the Cancer Genome Atlas (TCGA) Research Network, led by Dana-Farber scientist Matthew Meyerson, MD, PhD, examined the genomes, RNA, and protein from 230 lung adenocarcinoma samples. In three-quarters of the samples, the scientists ultimately identified mutations that put a cell-signaling pathway known as the RTK/RAS/RAF pathway into overdrive.

“Lung adenocarcinoma is the leading cause of human cancer death. This is because there are so many ways to develop the disease, and many different pathways are altered in this cancer,” said Dr. Meyerson. “In recent years, we have made enormous progress in lung adenocarcinoma treatment by targeting EGFR, ALK, and other mutated proteins. Through this study, we are able to add to the range of such alterations and therefore gain potential new therapeutic targets.”

Mutations affecting the RTK/RAS/RAF pathway can cause it to become stuck in the “on” state. As a result, signals that promote cancer cell proliferation and survival are produced continuously. However, drugs are currently available that curb aberrant activity of this pathway and prompt therapeutic responses in patients.

“About 10% of patients have tumors with EGFR mutations, and these patients uniquely benefit from anti-EGFR therapy,” said Alice Berger, PhD, a postdoctoral fellow in the Meyerson lab and coauthor of the study. “We were motivated to find genetic aberrations in patients that lack EGFR mutations and that might be similarly suitable for therapeutic targeting. Ultimately, we want to be able to provide every patient with an effective drug for their specific cancer.”

Oncogene Mutations Identified

In the group’s initial scan of the tumor samples, researchers identified oncogene mutations that would increase RTK/RAS/RAF pathway activity in 62% of the samples; these tumor samples were classified as oncogene-positive. To identify additional alterations, the investigators looked at DNA copy number changes, or changes in gene number resulting from the deletion or amplification of sections of DNA in the genome. In doing so, they detected amplification of two oncogenes, ERBB2 and MET, which are part of the RTK/RAS/RAF pathway in the oncogene-negative cancers. Gene amplification usually leads to increased expression of the encoded protein in cells.

Now that these amplifications have been identified in cancers without other activity of the RTK/RAS/RAF pathway, clinicians may be able to treat patients whose tumors have specific gene changes with drugs that are either currently available or under development.

“It is quite striking that we have now identified an actionable mutation in over 75% of patients with lung adenocarcinoma, a significant improvement from a decade ago,” said Dr. Meyerson.

Additional analysis identified other genes that may play important roles in lung cancer development. Mutations in one of these genes, NF1—a known tumor suppressor gene that regulates the RTK/RAS/RAF pathway—had previously been reported in lung cancer. Mutations of NF1 also put that pathway into overdrive. Another mutated gene, RIT1, is also part of the RTK/RAS/RAF pathway, and this is the first study to associate mutation of this gene with lung cancer.

“This is one of the most comprehensive studies of lung adenocarcinoma to date,” said coauthorJoshua Campbell, PhD, a postdoctoral fellow in the Meyerson lab. “The TCGA data enabled us to profile and analyze DNA, RNA, and methylation from over 200 tumors, and it made the discovery of these rare alterations possible.”

ANTIOXIDANTS PROBABLY HARMFUL IN CANCER

While alternative health gurus often encourage increasing antioxidants in the diet and the taking of antioxidant nutritional supplements such as beta-carotene, vitamins A, C, and E, and selenium, new research findings suggest that antioxidants could do more harm than good, especially in cancer patients.

The idea is discussed in a perspective article on the promise and perils of antioxidants for cancer patients in the July 10 issue of the New England Journal of Medicine.

Coauthor David Tuveson, MD, PhD, professor and deputy director of the Cold Spring Harbor Laboratory Cancer Center in New York, explained in an interview with Medscape Medical News that the idea that antioxidants could be useful in cancer goes back to Linus Pauling, and is based on observations that oxidation within cells is needed for cell growth. "As cancer cells growth rapidly, a cancer cell would have more oxidation within it than a normal cell," he added, and the hope was that antioxidants would interfere with these cellular oxidative processes and would suppress the growth.

"Although some early preclinical studies supported this concept," the authors write, there have now been several clinical trials that have shown no effect of antioxidants on reducing the incidence of cancer, and there have even been suggestions of harm in persons who are at risk for cancer.

Dr. Tuveson noted a clinical trial from Scandinavia in the early 1990s, which found that high doses of antioxidants, particularly beta-carotene, were associated with more lung cancer rather than less as had been hoped for.

There was a similar finding from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), which found that the antioxidants did not reduce the risk for prostate cancer, as had been hoped, and in fact increased the risk in some men.

Dose-dependent Harmful Effect

The perspectives article was prompted by new findings reported earlier this year, he said. An animal study carried out by Swedish researchers showed that the harm from antioxidants was dose-dependent (Sci Transl Med. 2014;6:221ra15). The study was conducted in a genetically engineered mouse model that mimics early human non-small-cell lung cancer. The researchers studied N-acetylcysteine (which is used in patients with chronic obstructive pulmonary disease) and also derivatives of vitamin E, and they found that these antioxidants "actually increased cancer burden and mortality in a dose-dependent manner."

"The mice got lung cancer faster and they died more quickly of the disease," Dr. Tuveson said.

In their perspective article, Dr. Tuveson and coauthor Navdeep Chandel, PhD, from Northwestern University in Chicago, address the question of why.

It turns out that all cells have not only oxidative mechanisms producing reactive oxygen species, they also have a mechanism by which they produce antioxidants, and so there is a balance between the 2 in each cell. "And cancer cells, because they make more oxidants, also make more antioxidants," Dr. Tuveson explained.

"So when adding an antioxidant as a supplement, all you are doing is increasing a pool of what is already there," he said. "But you are not actually stopping the oxidative mechanisms, and you are not stopping the production of oxidants in the first place, and the pathways that are fuelling cell growth," he added."All you are doing is helping the cancer cell deal with the toxic effects of the oxidants, and by doing so you may be actually making the cancer cell even stronger," Dr. Tuveson said."The antioxidants that we take as a supplement or in our diet don't go after the root cause of how oxidants promote cancer cell biology,...and our suggestion is that we need to look much more carefully at these mechanisms if we are to truly develop strategies to prevent cancer," he said.

In their article, the authors propose 2 strategies for further research — the development of antioxidants that target specific intracellular sites of oxidant production, and also a synthetic lethal strategy directed at antioxidants produced within the cell. Both of these strategies are currently at the research stage, with work focused on developing compounds that could be tested in humans.

As for the clinical implications of the research so far, Dr. Tuveson said: "We don't firmly say that taking antioxidants is dangerous for cancer patients...but I do believe that our article will cause those discussions to begin."

However, others have already warned cancer patients not to take antioxidants; for instance, prostate cancer patients have been warned against taking selenium, as previously reported by Medscape Medical News.

In addition, there is a question of whether antioxidants may interfere with common cancer treatments, such as chemotherapy and radiotherapy, as these work by increasing oxidation within cancer cells, Dr. Tuveson commented. This is an area that needs to be studied more, he said.

This issue of antioxidants being harmful to cancer patients was raised last year by Nobel laureate James Watson, PhD, who is chancellor emeritus at the Cold Spring Harbor Laboratory. He described a new hypothesis on reactive oxygen species that he considers is "among my most important work since the double helix."

Dr. Watson proposed that antioxidant levels within cancer cells are a problem and are responsible for resistance to treatment, and that the untreatability of late-stage cancer might be the result of "its possession of too many antioxidants."

"The time has come to seriously ask whether antioxidant use more likely causes than prevents cancer," Dr. Watson said. Nutritional intervention trials have shown no obvious effectiveness in preventing cancer or in lengthening mortality, and, "in fact, they seem to slightly shorten the lives of those who take them."

HIGH CHOLESTEROL MAY INCREASE BREAST CANCER RISK

A link has been found between high blood cholesterol and breast cancer risk in a large retrospective cross-sectional study,according to research presented at Frontiers in CardioVascular Biology 2014 in Barcelona, Spain.

However, the lead investigator cautioned that this is a preliminary finding, and experts have noted that the study did not control for obesity, which is known to be associated with breast cancer.

The study "only suggests an association between high cholesterol and breast cancer," said presenter Rahul Potluri, MD, from the Aston University School of Medical Sciences in Birmingham, United Kingdom.

He warned against overstating the findings. "Further research is required before anything can be confirmed. However, 10 to 15 years down the line, if further prospective studies confirm these findings, there is the possibility for a clinical trial on the use of statins in the prevention of breast cancer," he told Medscape Medical News.

Retrospective Analysis

Dr. Potluri said the team was prompted to study the possible link after research in mice suggested that lowering circulating cholesterol or interfering with its metabolism could be used to prevent or treat breast cancer (Science. 2013;342:1094-1098).

"We wanted to see if there were any associations between high cholesterol and breast cancer in a large sample," he explained.

He and his team conducted a retrospective analysis of a large clinical database of patient records from 2000 to 2013 in the United Kingdom.

Of the 664,159 women identified, 22,938 (3.5%) had high cholesterol and 9312 had breast cancer.

More women with high cholesterol than with normal cholesterol developed breast cancer (2.3% vs 1.4%)

In fact, having hyperlipidemia increased the risk for breast cancer by 1.64 times (95% confidence interval, 1.50 - 1.79).

"Further research is required to confirm this link before it can have any significance for patients," Dr. Potluri noted. "However, this provides a starting point."

Link Between Hypercholesterolemia and Breast Cancer No Surprise

"We have known for some time that obesity is associated with increased risk of breast cancer, especially in postmenopausal women," said Gabriel N. Hortobagyi, MD, professor of medicine in the Department of Breast Medical Oncology at the University of Texas M.D. Anderson Cancer Center in Houston, who was not involved in the study.

"There is also a large body of work that suggests that overweight or obese women with breast cancer have a higher risk of recurrence and death, despite receiving state-of-the-art treatment," he toldMedscape Medical News.

"There is also work that suggests that obesity and inflammation are linked and, of course, there is ample evidence that inflammation, obesity, and cardiovascular disease are linked. Obesity and the metabolic syndrome are also linked, so finding that hyperlipidemia and risk of breast cancer are associated is no surprise," he explained.

Dr. Hortobagyi also noted that data "suggest that patients with diabetes and breast cancer have a higher risk of recurrence, and that treatment of diabetes with metformin might be associated with reduced risk of recurrence of breast cancer."

On the basis of such data, Dr. Hortobagyi and his group are participating in a large adjuvant trial, led by the National Cancer Institute of Canada, looking at the addition of metformin to standard adjuvant therapy in primary breast cancer.

"That study has accrued more than 3500 patients but is not mature enough for analysis. This is an evolving story, and it is increasingly complex," he said.

CHOLESTEROL GUIDELINES

Coupled with the guideline changes—the most surprising of which was abandoning LDL-cholesterol targets in favor of identifying four specific groups of patients who benefit from moderate- or high-dose statin therapy—the cholesterol scene is made complicated because other clinical guidelines, including those from Europe and Canada, also offer advice on treating patients at risk for atherosclerotic cardiovascular disease (ASCVD).

Given the confusion and controversy, Dr Pamela Morris(Medical University of South Carolina, Charleston) and colleagues published a state-of-the-art review of the clinical practice guidelines for the management of LDL-related risk in the July 15, 2014 issue of the Journal of the American College of Cardiology ^[1].

In it, they summarize the existing clinical guidelines of the ACC/AHA, the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), the Canadian Cardiovascular Society (CCS), and the International Atherosclerosis Society (IAS), as well as clinical guidelines for the management of lipids in women, children, adolescents, and those with diabetes or chronic kidney disease (CKD). In doing so, they attempt to provide a clear picture of the guidelines' differences and similarities.

"It can be very confusing for healthcare providers," said Morris. "When I have a patient in my office, and it's a Hispanic woman who might have a little bit of renal insufficiency, what do I do? Do I follow the AHA guidelines for women, do I look to the CKD guidelines, or do I go to the ACC/AHA guidelines? There is some confusion regarding the multitude of available guidelines, and this confusion can result in suboptimal care of LDL-related risk."

Speaking with heartwire , Morris said that when she is speaking with other clinicians about the old and new clinical guidelines, the myriad of recommendations leads many of them to simply stay the course.

"They're doing the exact same thing they've always been doing," she said. "It's a barrier to change. So, hopefully, an article like this will help them understand previous guidelines and why the new guidelines were formulated. It will also help them understand that there are some similarities with the new guidelines, as well as some differences. I think if we can put it all in context, it might help them begin to implement new recommendations into their practice."

ACC/AHA Guidelines Launched in November 2013Reported by heartwire when they were published and later criticized, the ACC/AHA cholesterol guidelines recommend physicians treat four major primary- and secondary-prevention patient groups with statins. These four groups were selected because randomized, controlled clinical trials showed that the benefit of treatment outweighed the risk of adverse events. The four groups include:

• Individuals with clinical atherosclerotic cardiovascular disease.
• Individuals with LDL-cholesterol levels >190 mg/dL, such as those with familial hypercholesterolemia.
• Individuals with diabetes aged 40 to 75 years old with LDL-cholesterol levels between 70 and 189 mg/dL and without evidence of ASCVD.
• Individuals without evidence of ASCVD or diabetes but who have LDL-cholesterol levels between 70 and 189 mg/dL and a 10-year risk of ASCVD >7.5%.

The guidelines also recommend either moderate- or high-dose statin therapy, depending on the patient's risk. Those with ASCVD, for example, should be treated with a high-dose statin, such as atorvastatin 80 mg or rosuvastatin (Crestor, AstraZeneca) 40 mg, to achieve a 50% reduction in LDL-cholesterol levels.

To heartwire , Morris noted that while the new ACC/AHA practice guidelines abandon specific treatment targets, LDL remains the target of therapy, something it has in common with the other clinical guidelines. The majority of other practice guidelines continue to treat to specific LDL-cholesterol targets depending on patient risk and utilize low-dose statin therapy in certain patients (the US guidelines recommend low-dose statins only in those with a high risk of statin-related adverse events).

"LDL is still the lipoprotein of interest," said Morris of the 2013 ACC/AHA practice guidelines. "There might be variations in how you measure it. The big difference now is that there are no longer goals for how low to get it. And this is really unique to two sets of guidelines. It's unique to the ACC/AHA guidelines, and interestingly it's also a part of the new CKD guidelines, the new [Kidney Disease: Improving Global Outcomes] KDIGO guidelines. Again, in those guidelines, you start statin therapy at a fixed dose and there is no LDL-cholesterol goal."

New Risk Assessment Tool

In addition to coming under fire from those who believed the new guidelines opened the floodgates to treating more and more individuals with statins, especially those without ASCVD, the ACC/AHA guidelines had a rocky launch when two independent researchers reported that the algorithm used to assess the 10-year risk of ASCVD overestimated risk by 75% to 150% in three cohorts. The new risk-assessment calculator departs from the Framingham Risk Score (FRS) and was developed by an ACC/AHA expert panel who authored the 2013 guidelines for the management of patient risk.

"I think this change is important, that we now have a brand-new risk assessment tool," said Morris. "For decades we've been using different iterations of the Framingham Risk Score, whether it's the 10-year risk or lifetime risk. The new risk-assessment tool does have some limitations in terms of ethnic groups. It applies only to non-Hispanic whites and non-Hispanic African-Americans."

On the whole, however, the use of different risk calculators across the different guidelines makes sense, said Morris. These calculators should be tested and validated in the group of patients to which they are being applied.

Other Forms of Dyslipidemia

To heartwire , Morris said the older ATP III guidelines addressed how to treat most forms of dyslipidemia, including patients who would require a statin plus another LDL-lowering agent, such as cholesterol absorption inhibitors, bile-acid sequestrants, LDL apheresis, or newer drug therapies. The 2013 ACC/AHA guidelines are simplified and focus entirely on managing ASCVD risk caused by LDL cholesterol. Morris said this is appropriate given that this is where researchers have accumulated the most evidence. For example, there is very limited evidence supporting raising HDL or lowering triglycerides alone for the reduction of cardiovascular outcomes, she said.

The American Association of Clinical Endocrinologists (AACE) and the National Lipid Association(NLA) do not support the ACC/AHA guidelines, instead recommending that their members follow their own clinical guidelines for the management of cholesterol and CVD risk.

While Morris said she couldn't speak to why these two societies chose not to endorse the 2013 ACC/AHA guidelines, she suspects they still believe that treating to lower and lower goals still offers meaningful clinical benefits to the patient. In contrast to the ACC/AHA guidelines, which focused on randomized, controlled clinical trials only to support the recommendations, clinical lipidologists will often cite the totality of evidence, including animal and pathophysiologic studies of atherosclerosis, supporting lower LDL-cholesterol targets to decrease the risk of cardiovascular events.

17 Worst Habits for Your Heart

Here are the worst habits for your heart, and how to avoid them.

Bad habits for your heart

Everyone wants to have a healthy heart. Still, cardiovascular disease affects more than 1 in 3 adults in the United States.

The good news is that some simple, everyday habits can make a big difference in your ability to live a healthy lifestyle.

Here are the 17 worst habits for your heart, and how to avoid them.

Watching TV

Sitting for hours on end increases your risk of heart attack and stroke, even if you exercise regularly.

"Intermittent exercise doesn't compensate for the time you sit," says Harmony R. Reynolds, MD, associate director of the Cardiovascular Clinical Research Center at NYU Langone Medical Center, in New York City.

Why? The lack of movement may affect blood levels of fats and sugars.

Dr. Reynolds advises walking around periodically and, if you're at work, standing up to talk on the phone.

Leaving hostility and depression unchecked

Are you feeling stressed, hostile, or depressed? It can take a toll on your heart.

While everyone feels this way some of the time, how you handle these emotions can affect your heart health. “Those likely to internalize stress are in greater danger; research has shown a benefit to laughter and social support,” Dr. Reynolds says.

“And it’s helpful to be able to go to someone and talk about your problems.”

Ignoring the snoring

More than a minor annoyance, snoring can be a sign of something more serious: obstructive sleep apnea. This disorder, marked by breathing that is interrupted during sleep, can cause blood pressure to skyrocket.

More than 18 million Americans adults have sleep apnea, which increases the risk of heart disease. People who are overweight or obese are at higher risk for sleep apnea, but slim people can have it too.

If you snore and often wake up feeling tired, talk with your doctor; there are easy ways to screen for apnea, says Robert Ostfeld, MD, associate professor of clinical medicine at Montefiore Medical Center, in New York City.

Not flossing

While the exact reason is unknown, there is a strong link between gum disease and heart disease, Dr. Ostfeld says.

If you don’t floss, sticky, bacteria-laden plaque build up over time, which can lead to gum disease. One theory is that these bacteria trigger inflammation in the body.

“Inflammation promotes all aspects of atherosclerosis,” Dr. Ostfeld says. Treating gum disease can improve blood vessel function.

Withdrawing from the world

It's no secret that on some days, other human beings can seem annoying, irritating, and just plain difficult to get along with.

However, it makes sense to strengthen your connections to the ones you actually like. People with stronger connections to family, friends, and society in general tend to live longer, healthier lives.

Everyone needs alone time, but you should still reach out to others and keep in touch whenever you can.

You’re either all or nothing

Call it the Weekend Warrior Syndrome.

“I see so many people in their 40s and 50s dive into exercising with good intentions, hurt themselves, and then stop exercising all together,” says Judith S. Hochman, MD, director of the Cardiovascular Clinical Research Center at NYU’s Langone Medical Center.

With exercise, it’s wise to aim for slow and steady. “It’s more important to have a regular exercise commitment,” says Dr. Reynolds. “Be in it for the long game.”

Drinking (too much) alcohol

Sure, studies suggest a small amount of alcohol may be good for your heart. Alas, too many over-imbibe.

Excess alcohol is linked to a greater risk of high blood pressure, high levels of blood fats, and heart failure. In addition, the extra calories can lead to weight gain, a threat to heart health.

If you drink, stick to no more than two drinks per day for men, and no more than one a day for women. (One drink means a 12-ounce beer or 4-ounce glass of wine).

Overeating

Being overweight is a major risk factor for heart disease, and 72% of men and 64% of women in the U.S are overweight or obese.

Try to eat less, avoid oversize portions, and replace sugary drinks with water.

Dr. Reynolds and Dr. Hochman also suggest cutting portion sizes for high-calorie carbohydrates (think refined pastas and breads) and watching out for foods labeled “low-fat,” which are often high in calories.

Assuming you're not at risk

Cardiovascular disease—including stroke, heart disease, and heart failure—claims more lives in the United States than any other illness, including cancer.

"Don't assume you're not at risk," says Dr. Ostfeld.

High blood pressure and cholesterol, diabetes, being overweight, and smoking are all risk factors that should be kept in check.

Eating red meat

It’s best to think of red meat as an occasional treat rather than the foundation of a daily diet. Red meat is high in saturated fat, and there’s also evidence that processed meat, such as bacon and hot dogs, increases your risk of cardiovascular disease and colorectal cancer. Ideally, less than 10% of your diet should come from animals and animal products, Dr. Ostfeld advises.

Can’t part with the beef? Choose a lean cut of red meat and limit your intake. “People have to know that if you want a steak a few times a month, it’s OK,” Dr. Hochman says. “It’s what you’re eating three times a day that’s the issue. Be in it for the long haul. Eat a balanced diet.

Being a health procrastinator

Check in with an MD so that you know your numbers for cholesterol, blood pressure, and blood sugar.

If these are elevated, you're at risk for silent killers like heart disease, stroke, and diabetes.

One thought: The lifetime risk of developing hypertension, or high blood pressure, for adults in their mid-50s is approximately 90%, even with those who never had a problem before. "The general point is that just because you didn't have it at 24 doesn't mean you don't have it at 54," Dr. Ostfeld says.

Smoking or living with a smoker

Sure, you've heard it a million times before: Don't smoke. But it bears repeating.

"Smoking is a total disaster for your heart," says Dr. Ostfeld. Smoking promotes blood clots, which can block blood flow to the heart, and contributes to plaque buildup in the arteries.

It's also a smart bomb aimed at everyone around you, Dr. Ostfeld says. In fact, about 46,000 nonsmokers who live with a smoker die from heart disease each year because of secondhan

Stopping or skipping meds

Let's be honest: Taking pills is a pain. There can be side effects. And it's easy to forget your meds, especially if you feel fine.

"High blood pressure is called the silent killer because you don't feel it," Dr. Ostfeld says. "Saying you feel fine is not a justification for stopping these pills."

There are 30 types of high blood pressure medications, so there are choices if one isn't working, Dr. Hochman says. "If one medication doesn't work, we can try something else."

Avoiding fruits and vegetables

"The most heart-healthy diet is a plant-based diet," Dr. Ostfeld says. That means loading up on fruits and vegetables, nuts, whole grains, low-fat dairy, and protein, and keeping junk food to a minimum. In fact, new federal dietary guidelines recommend that half of each meal should be composed of fruits and vegetables.

Research has found that people who eat more than five servings of fruits and vegetables a day had about 20% lower risk of heart disease and stroke than people who ate less than three servings per day.

Ignoring physical symptoms

If you used to walk up three flights of stairs without a problem, but suddenly you're short of breath after one flight or have chest pressure, it's time to call your doctor—now. Never assume it's because you're out of shape.

Doctors say "time is muscle," meaning the quicker you get treatment for possible trouble, the less likely you are to have permanent damage to your heart muscle.

"It's better for it to be much ado about nothing than sitting on a heart attack for six hours," which is not uncommon, Dr. Ostfeld says

Being a salty snacker

The more salt you consume, the higher your blood pressure rises. One in three American adults has high blood pressure, a major risk factor for stroke, kidney failure, and heart attack.

“Steer clear of packaged junk food, read the labels for sodium content, and stick to the outer portions of the supermarket, which is where the fruits, vegetables, and (unsalted) nuts are,” Dr. Ostfeld says.

Most of us should keep sodium intake below 2,300 milligrams a day. If you have high blood pressure or are over 50, cut back to 1,500 milligrams.

Eating empty calories

Foods high in sugar, fat, and oil deliver calories, but very few—if any—nutrients your body can use.

Studies have shown that a diet full of empty calories increases the risk of obesity and diabetes.

Look for foods dense in nutrients, such as vegetables, fruits, whole grains, seafood, eggs, beans and peas, and unsalted nuts and seeds. Lean meats and poultry, along with fat-free and low-fat milk, are good choices as we

Almonds

Almonds are extremely good for health as they are packed with phyto-chemicals. Almond nuts are very rich in vitamins, miners and dietary fibre. Eating almonds is a very good way to increase your Good Cholesterol and lower your bad cholesterol. Almonds are very rich in Vitamin E. Almonds are absolutely gluten-free and hence can be taken by people who have wheat allergy or celiac disease. Almond oil if applied regularly can prevent skin dryness. Eating a handful of almonds everyday ensures you get your daily source of Vitamins, Minerals and Proteins.

Asparagus

Asparagus belongs to the Lily Family as do tulips, garlic as well as onion. There are about 300 species of Asparagus in the world, the best known of which happens to be garden asparagus or asparagus officialisms. A lot of countries including UK, Germany, New Zealand, Australia, USA, Mexico, Thailand and China grow Asparagus. Asparagus is low on saturated fat and the cholesterol content is also extremely low. Asparagus is a very good source of Calcium, vitamin B6, Zinc as well as Magnesium. The shoots of Asparagus are generally stir-fried and served as appetizers or as vegetable side dishes. You can even pickle Asparagus and store for a long time.

Avocado

Avocado is called Alligator pear due to its green skin, rough texture and size, especially the Hass Avocado. There are about 80 types of avocados and Hass avocado is the most common one of them all. Avocados were used instead of butter by the European sailors. Avocados are rich in potassium, fibre and vitamins K, C, B6 and folate. You can get about 160 calories by eating half of an avocado. Avocados are good sources of antioxidants and therefore it is a good idea to include avocado oil or avocado in your salads

Basil

Basil happens to be a powerful herb with great aroma and pleasant taste. Basil is part of the mint family and it is native to Asia. Basil is very good for digestion and it is a great anti-gas aid. Basil tea can ease your anxiety and provide relief to headaches. It has sedative properties. Basil can prove effective to gain relief from stomach cramps. It can also ease constipation. Basil leaves contain compounds like eugenol, linalool, citronellal etc., that have anti-bacterial and anti-inflammatory properties. Basil is very rich in vitamin A, Vitamin K and minerals like copper, potassium, magnesium and manganese.

Chocolate

Chocolate has been derived from ‘’Xocolatl’’ which in Aztec stands for “bitter water”. Dark chocolate is healthier than white chocolate because it contains more of cocoa and less of sugar. Dark chocolate reduces blood pressure and improves the cardiovascular health as it contains a lot of antioxidants. You can experience relaxation by just smelling a chocolate as this is smell is supposed to increase the theta brain waves. Chocolate has less of caffeine and it helps to avoid the bad cholesterolChocolate makes you feel absolutely great and even helps you to live longer

Garlic

Garlic is amongst the oldest cultivated crops. The builders of the Great Pyramid would eat garlic for strength. During the First World War, garlic used to be used like an antiseptic to treat gangrene. Cervical cancer was treated through garlic vapours in ancient Greece. Garlic can be really beneficial while fighting diabetes, heart disease, cancer and various kinds of illnesses and infections. External wounds can be dressed using crushed garlic as it has antiseptic as well as antibiotic properties.

Eggs

Eggs are a natural source of vitamin D. Eggs can actually absorb odours and flavours as they have about 17,000 pores on their surface. .If you accidentally drop an egg on your floor, sprinkle a lot of salt on it to clean it up easily. The colour of the egg yolk usually depends upon the diet of the hen. Eggs are nutritious not only for humans but for pets too. Eggs are in fact great to maintain animal fur, coat health and even eyesight. For vegetarians, eggs happen to be a very essential source of complete protein