Cholesterol Altering Drugs: Niacin and Niaspan

Statin type medications are known for their powerful effect on lowering LDL. Fibrates are specifically effective in lowering triglycerides. But neither have much an effect on the HDL. Raising HDL is of benefit in lowering the risk of heart disease. The cholesterol lowering effect of niacin, actually vitamin B-3, was first reported in 1955. As a general cholesterol drug, niacin has it all. In doses well above the vitamin requirement (about 50 mg per day), niacin can lower LDL and lower TG, but in particular it increases the HDL more than any other drug. Given in combination with a statin, niacin can lower the LDL more than any other drug combination.
Thus, you may prescribe niacin specifically to help increase HDL as well as lower the LDL (“up with the good and down with the bad”). The mechanism of action for niacin is not well understood but it may inhibit the release of free fatty acids from adipose tissue and thus increase the production of an enzyme called lipoprotein lipase; this in turn likely increases the rate of TG removal from the blood. Niacin has also been shown to reduce the synthesis of LDL in the liver. Indirectly, by increasing the amount of HDL, its action in what is called “reverse cholesterol transport” actually enhances the return of LDL to the liver and out of the circulation.
1. Common Names: there are a number of niacin preparation – so called “slo-niacin” has been questioned to be of any value in lowering cholesterols; however, the other preparations do have the desired therapeutic effect. There is immediate release niacin, extended release niacin, and (in prescription form only and the most effective) sustained release niacin (Niaspan).
2. Effect on Cholesterols: decrease LDL 5%-25%, raise HDL 15%-35%, decrease TG 20%-50% - the effect on TG is enhanced on a low carbohydrate type, weight loss diet; however, be aware that since niacin (except for Niaspan) is available from many sources including the internet and the health food store (actually a “nutraceutical” rather than a “pharmaceutical” and thus not strictly regulated) you may not always get what you pay for – so choose wisely; Niaspan, made by KOS Pharmaceutical on the other hand is strictly regulated as required by law.
3. Side Effects: the most common is flushing (potentially relieved by taking an aspirin 30 minutes before the dose) and gastrointestinal upset (can be reduced by taking dose with a low-fat snack such as yogurt); studies do indicate that niacin may increase blood sugar, but on the other hand it is a very useful medication in diabetics; niacin can increase the potential for gout and has a small risk of causing increases in liver enzymes, especially when combined with statins.
4. Usage: the frequency of dosing depends on the preparation – the immediate release and extended release niacin are taken generally twice per day; Niaspan is taken once per day.
5. Contraindications: an absolute contraindication is chronic liver disease; relative contraindications are gout, diabetes, and ulcer disease; liver blood tests should be monitored especially if also taking statin type medications.

Red Yeast Rice Reduces LDL-Cholesterol Levels in Statin-Intolerant Patients

According to the results of a new study, the use of red yeast rice and a therapeutic lifestyle change significantly reduced LDL-cholesterol levels in statin-intolerant patients with dyslipidemia and may provide a future treatment alternative for these difficult-to-treat patients. The results of the study are published in the June 16, 2009 issue of the Annals of Internal Medicine. "If properly regulated, I would say it's time that we began using red yeast rice in these statin-intolerant patients," said lead investigator Dr David Becker (Chestnut Hill Hospital, Flourtown, PA).

Extracts of red yeast rice have been widely used in China for therapy in patients with circulatory and digestive disorders for centuries, and preparations of red yeast rice have been shown to lower plasma LDL levels. Lovastatin occurs naturally in certain forms of red yeast rice that are made when the rice is cultivated with the mold Monascus purpureus. Red yeast rice is readily available in health food stores and over the internet, with US sales of $17 million in 2006.
In this study, 62 patients with dyslipidemia and a history of stopping statin therapy due to myalgias were randomized to receive 1800 mg of red yeast rice or placebo twice daily for 24 weeks. All patients were concomitantly enrolled in a 12-week therapeutic lifestyle-change program that included eating a Mediterranean-based diet, an exercise program, and relaxation techniques. The mean number of statins tried before the intervention was two.

After 12 weeks of treatment, LDL- and total-cholesterol levels were significantly lower in the red-yeast-rice group when compared with the placebo-treated patients. HDL-cholesterol levels were unchanged with treatment, and triglyceride levels were not significantly different between treatment arms. LDL- and HDL-cholesterol levels increased slightly from weeks 12 to 24, likely because the lifestyle intervention program ended and adherence to therapy declined, note investigators.

"The traditional approach among cardiologists is to patiently, or not so patiently, try one statin after another until they find a drug they can tolerate, because we know that they have to take this medication." said Becker. In the study, just two patients developed persistent intolerable myalgias. Becker noted that when patients develop myalgias with one statin, 40% to 60% typically end up stopping a second or third statin. Pain scores, derived from a self-administered questionnaire, were similar in both treatment arms at 12 and 24 weeks.

Becker noted that the dose of red yeast rice used in the study is equivalent to a daily lovastatin dose of just 6 mg, much less than established therapeutic doses of 20 mg to 40 mg, and that the amount of LDL lowering observed in the trial is disproportionate to such a low dose. Asked why red yeast rice was so well tolerated and yet so effective, Becker said that red yeast rice contains monacolin K, which is the naturally occurring lovastatin, but also numerous other monacolins that might work to lower LDL-cholesterol levels without causing recurrent muscle pain.

Investigators urged caution about moving these results into clinical practice, however, specifically pointing out that while the chemical composition of red yeast rice was known and controlled in this study, there is a lack of consistency between different manufacturers and an ongoing need for the Food and Drug Administration to better regulate this popular dietary supplement.

Krill Oil – Just the Facts

Undoubtedly, you heard about Krill Oil on Oprah or in Readers Digest. I am a proponent of omega-3 fish oil which I recommend it to most patients. Omega-3s have been shown to play a key role in heart health, from reducing triglycerides and blood pressure to inhibiting inflammation.

Recently it has been suggested that krill oil might be even better than fish oil for heart health. This marine oil is produced from shrimplike krill harvested from Antarctic waters and contains significant amounts of the omega-3 fatty acids EPA and DHA, as well as phospholipids (which are integral to the building of cell membranes) and potent antioxidants, including astaxanthin, a carotenoid from the nutrient family that includes beta-carotene, lycopene and lutein.

Krill oil has become widely touted not only because it may help to lower total and LDL cholesterol, but also because it could help with arthritic joint pain and the physical and emotional symptoms of premenstrual syndrome (PMS). Of the 85 species identified worldwide, apparently it is only the Antarctic krill (Euphausia superba) that is the source of the powerful oil.

No one is quite sure how krill oil works for reducing cholesterol. But in a 12-week study involving 120 men and women ages 25 to 75, Canadian researchers tested the effects of krill oil (Neptune krill oil was used in the study) vs. fish oil on elevated blood lipid levels and found that it LDL cholesterol by 34% and increased HDL cholesterol by 43.5% compared to the placebo. In comparison, fish oil reduced LDL cholesterol by 4.6% and increased HDL cholesterol by 4.2%. Krill also lowered triglycerides. In the study, a dose of 1 to 1.5 grams of Neptune krill oil a day was significantly more successful at lowering LDL and triglyceride levels than a dose of fish oil three times greater (3 grams). Krill oil at higher doses (3 grams) also lowered blood triglycerides, while fish oil did not. Researchers theorize that the unique molecular structure of krill oil that gives it its potent effects.

In general, fish oil has not been found to lower LDL cholesterol unless it is substituted for dietary saturated fat that, by itself, increases LDL. I would not recommend krill oil or other omega-3s for the purpose of lowering LDL. But as a way of increasing your overall intake of omega-3s, with some other potential health benefits, it looks promising.

Preliminary research also suggests krill oil may help reduce symptoms of PMS, however, more research is needed. It is also noteworthy that a study in the Journal of the American College of Nutrition found that krill oil was effective at reducing arthritis symptoms and inflammation.

People with allergies to seafood or bleeding disorders shouldn't use krill oil. Side effects may include loose stools, diarrhea or indigestion. Unlike fish oil, it does not become rancid at room temperature, and causes no fishy “burps.” I suggest looking for a product that contains Neptune krill oil (NKO), since it is the krill oil that was used in the cholesterol study. A dose of 1,000 milligrams of krill oil a day could prove useful for lowering total cholesterol and improving triglycerides. A dose of 500 milligrams once a day may help maintain good cholesterol levels once you achieve them. If your patient is already taking a statin, however, don’t stop in favor of krill oil.

Rheumatoid Arthritis Increases Heart Attack Risk

A diagnosis of rheumatoid arthritis doubles the risk of having a heart attack within the next 10 years, according to Swedish researchers presenting their findings this week at the annual meeting of the American College of Rheumatology in San Francisco. But that disturbing news was tempered by other research which showed that medications to lower cholesterol may lower the risk and that all but one commonly used medication to treat RA also appear protective of the heart. About 1.3 million Americans have RA, according to the American College of Rheumatology. Women are twice as likely as men to be affected.

The increased risk of heart attack and other cardiovascular problems in patients with rheumatoid arthritis has long been known. "What we haven't known before is when in the RA disease process this increased risk is manifest," says Marie Gunnarsson, a doctoral student at Karolinska Institute in Stockholm, who is presenting the study findings. Her team used the Swedish RA Register to identify 7,954 patients newly diagnosed with RA and matched them with 38,913 people from the general population. They followed both groups for more than 10 years, beginning in 1995, collecting data on heart attacks, death from heart attacks, and other causes.

They computed the average rate at which the heart attacks and deaths happened. From the time of diagnosis to the first 10 years after it, the risk of heart attack and death from heart attacks nearly doubled in the RA group. At the time of diagnosis, the patients were no more likely to have a heart attack history than the control group. Gunnarsson says the new finding supports the idea that the disease itself has something to do with the development of heart problems. The inflammation that occurs with RA could be driving up the risk, she says.

In other research, investigators from the United Kingdom and the Netherlands tried to put in perspective which risk factors for RA patients are most important in predicting heart attack. Among them:

• Heart disease risk factors such as high blood pressure, smoking, and excess weight
• The use of RA medications
• The use of cholesterol-lowering medications

There has been uncertainty about which factors are most important in the risk of developing heart disease in individuals with RA. They found that those with RA had 6.49 heart attacks per 1,000 people per year, while those without had 2.96 per 1,000 people per year. The chances of having a heart attack among those with RA, overall, were less in those who took medications for RA. Researchers looked at drugs known as DMARDs (disease-modifying antirheumatic drugs) as well as prednisolone.

When they looked individually at the medications, they found that all the DMARD medications were protective of the heart but that prednisolone modestly increased the risk. When they took into account risk factors such as high blood pressure, the effects were no longer significant. The researchers also found that cholesterol-lowering medication lowered the rate of heart attack by 25%, but that blood pressure medicines had no significant effect. The presence of the rheumatoid arthritis itself seems to be the biggest risk factor for heart problems.

The research also suggests that the traditional risk factors for heart disease are very important for people with RA, he says, as well as the increased risk from having RA.

Statin Benefits Patients With Low Cholesterol

A large study suggests that millions more people could benefit from taking statins, even if they have low cholesterol, because the drugs can significantly lower their risk of heart attacks, strokes and death.

The study, involving nearly 18,000 people worldwide, tested statin treatment in men 50 and older and in women 60 and older who did not have high cholesterol or histories of heart disease. What they did have was high levels of high-sensitivity C-reactive protein, or CRP, which indicates inflammation in the body. The study, called the Jupiter study, was presented Sunday at an American Heart Association convention in New Orleans. It found that the risk of heart attack was more than halved for people who took statins and they were 20 percent less likely to die during the study. The statin was considered so beneficial that an independent safety monitoring board stopped what was supposed to be a five-year trial last March after less than two years. "Physicians can no longer assume that a patient with low cholesterol has a low risk for a heart attack or stroke," said lead researcher Paul M. Ridker, MD, of Boston's Brigham and Women's Hospital.

Scientists said the research could provide clues on how to address a long-confounding statistic: that half of heart attacks and strokes occur in people without high cholesterol. Several experts said that although the research was significant and would affect clinical practice, the study as published did not give enough detail about which patients should now be tested for CRP or given statins. Like many clinical trials, the study was sponsored by AstraZeneca. It makes the drug in the trial, rosuvastatin, which is sold as Crestor. The most potent statin on the market, Crestor has been criticized by consumer health advocates who say it is more likely to lead to muscle deterioration and kidney problems.

Others say cholesterol is much more important. Dr. Scott Grundy, a heart expert at the University of Texas Southwestern Medical Center, pointed out that in the Jupiter study, the statin not only lowered the protein but also significantly cut already low cholesterol levels, raising questions about whether the benefit actually came from giving patients superlow cholesterol. And because CRP can rise with short-term infections unrelated to chronic inflammation, some experts said test results needed to be weighed against other aspects of the patient’s health.

The issues here are that these study participants were average age 66 people who has a higher than normal BMI (28) but had a 'normal' cholesterol - again, these were NOT low risk people, just low cholesterol. The study shows that the benefits of taking drugs such as Crestor can apply across a broad range of individuals and, as we have known for some time, half the people that have heart attacks have a 'normal' cholesterol - so this is not a particularly powerful discriminator.

The problem is that using such measures of 'risk' across a population does not imply that you as an individual have a higher or lower risk; the best way to define risk is first to refine your risk by doing a heart scan and THEN define factors that contributed to this such as higher than necessary cholesterol.

Thus, the problem with these and many other studies is that they tell you who might be at risk but do not tell you the potential risk in a given individual which is best done by doing a heart or vascular scan.

John A. Rumberger, M.D., FACC

Medical Director, PrevaHealth

Too Little Vitamin D Puts Heart at Risk

Researchers say a growing body of evidence suggests that vitamin D deficiency increases the risk of heart disease and is linked to other, heart disease risk factors such as high blood pressure, obesity, and diabetes. For example, several large studies have shown that people with low vitamin D levels were twice as likely to have a heart attack, stroke, or other heart-related event during follow-up, compared with those with higher vitamin D levels.

Most of the body's vitamin D requirements are met by the skin in response to sun exposure. Other less potent sources of vitamin D include foods such as salmon, sardines, cod liver oil, and vitamin D-fortified foods like milk and some cereals. Vitamin D can also be obtained through supplements. Recent studies have shown that low levels of the vitamin may predispose the body to high blood pressure, congestive heart failure, and chronic blood vessel inflammation. It also alters hormone levels to increase insulin resistance, which raises the risk of diabetes.

In a review article published in the Journal of the American College of Cardiology, researchers surveyed recent studies on the link between vitamin D deficiency and heart disease to come up with practical advice on screening and treatment. They concluded that vitamin D deficiency is far more common than previously thought, affecting up to half of adults and children in the U.S. Researchers say higher rates of vitamin D deficiency may be due in part to spending more time indoors and the use of sunscreens. Sunscreen with a sun protection factor (SPF) of 15 blocks approximately 99% of vitamin D synthesis by the skin.

Vitamin D levels can be measured with a blood test that looks at a specific form of vitamin D called 25-hydroxy vitamin D (25(OH)D). Researchers recommend 25(OH)D screening for those with known risk factors for vitamin D deficiency including:

• Older age
• Darkly pigmented skin
• Reduced sun exposure due to seasonal variation or living far from the equator
• Smoking
• Obesity
• Kidney or liver disease

The U.S. government's current recommended daily allowance (RDA) for vitamin D is 200 (IU) per day for individuals under age 50. For those between 50 and 70, 400 IU per day is recommended, and for those over age 70, the RDA is 600 IU. Most experts believe these doses are too low, and that somewhere between 1,000 and 2,000 IU of vitamin D per day is necessary to maintain adequate vitamin D levels. The safe upper limit of vitamin D consumption is 10,000 IU per day. Vitamin D supplements are available in two different forms: Vitamin D2 and Vitamin D3. Although both appear effective in raising vitamin D blood levels, Vitamin D3 supplements appear to be longer-lasting.

Although there are no current guidelines for restoring and maintaining healthy vitamin D levels in people at risk for heart disease, for those who are vitamin D deficient, the researchers recommend initial treatment with 50,000 IU of vitamin D2or D3 once a week for eight to 12 weeks, followed by maintenance therapy.

Metabolic Syndrome May Predict Depressive Symptoms

The presence of the metabolic syndrome predicts depressive symptoms in middle-aged adults, according to the results from the prospective Whitehall II cohort study reported in the December 23 Online First issue of Diabetes Care.

"Although it is possible that the association between depression and the metabolic syndrome is a 'two-way street,' the metabolic syndrome as a predictor of depression has been little investigated," write Tasnime N. Akbaralya, PhD, from the University College London, in London, United Kingdom, and colleagues. "We examined whether the metabolic syndrome is associated with the onset of depressive symptoms in a cohort of middle-aged British civil servants."

The study cohort consisted of 5232 participants, aged 41 to 61 years, in whom depressive symptoms were evaluated from 1991 to 1993 and again 6 years later, with use of the depression subscale from the 30-item General Health Questionnaire. At baseline, metabolic syndrome was evaluated based on National Cholesterol Education Program criteria.

After adjustment for potential confounders, the presence of the metabolic syndrome was associated with an increased risk for future depressive symptoms (odds ratio, 1.38; 95% confidence interval, 1.02 - 1.96). Central obesity, high triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels, but not other components of the metabolic syndrome, predicted depressive symptoms and accounted for most of the association between the metabolic syndrome and the onset of depressive symptoms.

"Our results suggest that the metabolic syndrome, in particular the obesity and dyslipidemia components, is predictive of depressive symptoms," the study authors write. "Our findings are consistent with the hypothesis that depressive symptoms may be a consequence rather than a cause of the metabolic syndrome."

Potential limitations include measurement of depressive symptoms with use of a short scale that is not a measure of clinically recognized psychiatric disorder; limited generalizability of the findings because Whitehall II study participants are mainly white, office-based civil servants; and possible unmeasured confounders.

"This is apparently the first study to show that the probability of new onset depressive symptoms 6 years later is higher amongst men and women with the metabolic syndrome; an association that remains after taking into account a large range of potential confounders," the study authors conclude. "Further research is needed to examine whether prevention of the metabolic syndrome, in particular its obesity and dyslipidemia components, might reduce the onset of depressive symptoms."

Burning Questions About Metabolism

On the topic of metabolism and weight loss, conflicting information abounds. Here are the highlights of some recent studies:
Does too much restriction of food intake really slow one’s metabolism? If so, how much and at what level of calorie reduction does this kick in?
On the first question: Yes, which is among the many reasons why starvation diets don’t work. Any time a person drops below 1,200 calories a day, the body shows signs of slower basal metabolism,” Research shows anything less than 1,000 calories per day would prompt slower metabolism. As soon as you cut calories significantly, you’re not the same person metabolically.
Does the number of meals you eat impact your metabolic rate?
No, but it can impact hunger and energy levels. Eating 7 meals a day was the same as eating 2 meals a day, so long as total calorie intake was the same. There is also evidence that small, frequent meals stabilize glucose levels — which in turn can control hunger. Keeping insulin and glucose at a steady state is the best way to maintain a ‘healthy’ metabolism.
Does working out harder extend your metabolic burn beyond the time of the workout itself? For example, does it extend the calorie burn deeper into the day if you work out hard for 20 minutes rather than for 20 minutes moderately?
Yes. The exercise afterburn effect directly affects metabolism and is stronger after a hard workout. Intensity is more important than duration, according to a 2003 Norwegian study. For a few hours after a hard workout, your hourly calorie burn rate would equal 15% to 20% of the total calories used during the workout. A moderate workout would yield only a 10% post workout calorie burn. For instance, someone who did step aerobics for 30 minutes and expended 400 calories would have an afterburn effect of 60 to 80 calories per hour. And a person who walked for an hour and burned 500 calories would have an afterburn effect of about 50 calories.
Are there supplements and herbs that can increase metabolism?
Yes, but there’s not a lot of solid science behind them. Green tea and caffeine are the most studied supplements in terms of metabolic boost. A 2007 study in the journal Obesity that found drinking a beverage containing green tea catechin, caffeine and calcium 3 times a day increased 24-hour energy expenditure by 4.6% in healthy, young, lean men and women. The real value of these supplements is not that they ‘increase’ metabolism but rather that they help to prevent metabolism from dropping as you lose weight.
Are there really foods that increase metabolic burn?
No foods have the magical quality to burn the calories away. However, there is a thermic effect to food — the digestion process burns calories and boosts metabolism. Protein has the highest thermic effect, followed by carbohydrates. Fat has almost no thermic effect. A Dutch study that concluded that eating omega-3 fats can boost metabolism, while saturated fat consumption slows metabolism.

Again, remember the bottom line: Fresh produce, whole grains, lean protein and low-fat dairy are better than processed, sugary foods. And to lose weight, you must burn more calories than you consume. And that is a clear message we can give our patients.

Content adapted from Revolution Health Group

Depression, Anger and Hostility Markers for CVD

Two studies published in the March 17 edition of the Journal of the American College of Cardiology conclude that depression, anger, and hostility may be red flags of heightened heart disease risk, even if you don't have heart disease right now.

The studies noted that sudden cardiac death may be more than twice as common among women with symptoms of major depression than women who aren't depressed. This finding comes from a study of more than 63,000 U.S. female nurses followed from 1992 to 2004. The nurses had no history of heart disease when the study started. The study also linked sudden cardiac death to antidepressant use, but it's not clear if that's related to the drugs or the depression.

It was also shown that chronically angry or hostile adults with no history of heart disease may be 19% more likely than their peers to develop heart disease are 24% more likely than other heart disease patients to have a poor prognosis. These findings came from reviewers who pooled data from 44 studies conducted in America, Europe, Asia, and Australia between 1983 and 2006.

The reports don't prove that depression, anger, or hostility caused heart disease. But the findings held regardless of other heart disease risk factors, suggesting a stubborn link among those traits. "There is clearly a link between depression, anger, anxiety, stress, and outcomes in heart disease," says Philip Binkley, MD, FACC, professor of medicine at The Ohio State University.

Redford Williams, MD, director of the Behavioral Medicine Research Center at Duke University says that he "absolutely" considers chronic anger, hostility, or depression to be risk factors for heart disease, just like hypertension or high cholesterol. Cardiologist Pamela Douglas, MD, of Duke University, also sees a strong link between depression and heart disease but she says it's not clear which comes first, depression or heart disease. "It's sort of a chicken-or-the-egg issue," Douglas says.

All three experts agree that other heart disease risk factors often accompany depression -- and it never hurts to screen for heart hazards. And if you know your patient has heart disease, they should be screened for depression, according to guidelines set in September 2008 by the AHA.

As noted earlier, the new report on depression and heart disease showed a possible link between antidepressant use and the risk of sudden cardiac death. "The question is, is that just because the antidepressants were a sign of a more severe depression or was it a result of something about the antidepressants themselves?" Williams asks.

Williams notes that some tricyclic antidepressants are known to have effects on cardiac arrhythmias. But the new report doesn't show what kind of antidepressants the patients were taking or other details about their antidepressant use. Douglas agrees that the antidepressant findings aren't clear and says, "Don't take 'em if you don't need 'em." Douglas and Binkley say studies haven't proven that treating depression (or hostility and anger) eases heart disease.

It is worth remembering that EBT has been shown to have a negative predictive value approaching 100%. The test can be completed in minutes without drugs or preparation. It is one-third the cost of stress nuclear imaging and up to one-half the cost of stress echocardiography. Thus, peace of mind or a precise clinical plan for addressing problems can help reduce patient’s anxiety and help protect their good health.

J.A. Rumberger, M.D. FACC

Medical Director, PrevaHealth

Frequency of ‘Silent’ Heart Attacks

Undiagnosed, or "silent," heart attacks affect nearly 200,000 people in the United States annually. As many as 40 to 60 percent of all heart attacks are unrecognized according to a new study from Duke University Medical Center. Even if a heart attack occurred in the distant past, it may still leave a signature called a Q-wave on an electrocardiogram. But there are silent heart attacks that do not have associated Q-waves.

By definition, a heart attack usually occurs when a clot obstructs blood flow from a coronary artery to the heart. This may cause severe chest pain, shortness of breath, fainting and nausea. But sometimes a heart attack is not painful, or the person experiencing it does not recognize the symptoms as heart-related, so he or she does not go to a hospital for treatment. Cardiologists have only recently become attuned to the prevalence of these silent heart attacks, and research on treatment is limited. The risk factors for silent heart attacks are the same as for regular heart attacks, experts say, and include smoking, diabetes, stress and family history.

Researchers at Duke University Medical Center used a relatively new technique called delayed-enhancement cardiovascular magnetic resonance and then followed up with patients after about two years. The study was done on 185 patients who had never had a diagnosed heart attack but were suspected of having coronary artery disease. The researchers found that 35 percent of patients had evidence of a heart attack and that silent heart attacks without Q-waves were three times more common than those that had Q-waves. Patients with non-Q-wave silent heart attacks also had 11 times higher risk of death from any cause and a 17-fold risk of death from heart problems compared with patients without any heart damage.

Dr. Han Kim, a cardiologist at Duke University and lead author of the study said "If you don't know when an actual event occurred, it becomes difficult to prescribe therapy." Treatment for someone who has had a silent heart attack is usually the same for someone who came to the hospital immediately after a heart attack, Kim said. This may include beta blockers, statin drugs, aspirin or other medications.

Researchers noted that patients with non-Q-wave silent heart attacks were also generally older and were more likely to have diabetes. There needs to be more of a focus on prevention among these risk groups, said Dr. David Wiener, a cardiologist at the Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, who was not involved in the study

Once again these studies underscore the importance of identifying those with the disease, stratifying their risk and beginning interventions designed to reduce the rate of development of atherosclerosis as soon as possible. statin and micronutrient therapies have proved to be effective when managed under the care of a physician. EBT remains the earliest modality for the detection and quantification of coronary calcium available anywhere.

J.A. Rumberger, M.D. FACC

Medical Director, PrevaHealth

Omega-3 Fatty Acids - FISH OIL for Heart Prevention - the Facts!

In the 1970's, studies in Greenland Eskimos showed 1/10 the incidence of heart disease compared to an ethnically similar population in Denmark. Both populations had a comparable and even high intake of total fat (42% of dietary calories) but the intake of omega-3 polyunsaturated fat (PUFA) or "fish oil", was 4-times as much in the Eskimos. A more recent study in the US Physicians Health Study showed that consuming at least 1 fish meal per week reduce the risk of sudden cardiac death by 52% compared with those consuming fish only monthly. One recent study also showed that omega-3 intake reduced the risk of stroke.

Omega-3 PUFA can be derived from a diet rich in α-linolenic acid (legumes, leafy vegetables, flax, flaxseed oil, canola oil) or directly via eichosapentaenoic acid (EPA) and DHA (docosahexenoic acid) from fish oil or direct supplements. EPA and DHA are the major omega-3 PUFA’s and are thought to be responsible for the heart protective effects. The table below summarizes the results of 4 large scientific studies.

Study	Dietary Modification	Effect on Mortality
Finnish Mental Hospital Study	Replacement of fat with polyunsaturated fat	53% decrease in men and 34% decrease in women
Lyon Diet Heart Study	Low saturated fat and high α-linolenic acid diet	65% decrease over 4 years
DART (diet alone and reinfarction trail]	Supplementation with fish oil (1-2 gm/day)	33% decrease
GISSI [Italy]	Supplementation with fish oil (1-2 gm/day)	20% decrease

Remember that these dramatic effects were found in patients already known to have heart disease ["secondary prevention"]. Data are still sparse on the value of PUFA for "primary prevention" - but most experts feel that a diet of fish at least once per week, or alternatively supplementation with "fish oil" capsules can be part of a heart protection program. The American Heart Association recommends omega-3 in some form as part of the prevention program in women. However all “fish oil” capsules are not the same. The amounts of the active ingredients EPA and especially DHA determine efficacy. It is suggested that that the total amount of combined EPA and DHA (taken, as with all supplements, in two-divided daily doses) should be on the order of 1,200 mg per day. This can be confusing to the consumer who finds a “1,000 mg” fish oil capsule to contain only 500 mg or less of combined EPA and DHA.

Your patients with an allergy to fresh-water fish should NOT take these supplements. Also, they have mild effects on increasing blood sugar levels, but the risk versus the benefit is very low. Omega-3 supplementation does not increase LDL values, although it may increase the HDL, a small amount and it may also help change the more dangerous “low-dense” LDL particles into the less dangerous “large-fluffy” particles. Higher doses (combined EPA and DHA of about 3,000 mg per day or more) can lower the blood triglyceride levels. In patients with high triglycerides, I recommend supplementation with higher doses of fish oil. Some evidence indicates that Omega-3 also may have some cancer preventing effects, may slow down the development of Alzheimer’s, and may even have some benefit in reducing depression. Finally, recent data also show that omega-3 from any source has anti-inflammatory (and thus anti-oxidative stress) effects.

John A. Rumberger, M.D., FACC

Chronic High Anxiety May Hurt Heart

A study in the Journal of the American College of Cardiology suggests that chronic high anxiety may raise heart disease patients' odds of dying or having a heart attack. Based on the study's findings, doctors should monitor and try to ease heart disease patients' anxiety, note the researchers, who included cardiologist Charles M. Blatt, MD, FACC, of Harvard Medical School.

"Most patients come in very anxious about their coronary condition," Blatt says in an American College of Cardiology news release. "I'm convinced that spending time with the patient and the family and interacting with them as a caring human being is critically important to clinical outcomes," Blatt says. "My hunch is that for the majority of patients, the greatest anxiety-reducing effect comes from having a good relationship with a doctor."

Blatt's team studied 516 people with coronary artery disease. The coronary arteries supply blood to heart muscle; coronary artery disease makes heart attacks more likely. The patients were 68 years old, on average; roughly eight in 10 were men. At the study's start and every year for up to five years, the patients completed a survey about how they had felt in the previous week, ranging from "peaceful" to "feeling that something bad will happen."

The survey also covered patients' recent sleep problems and upset stomachs. Blatt's team followed the patients for about three years, on average. During that time, 19 patients died and 44 had nonfatal heart attacks. The researchers calculated the patients' anxiety score on each survey, as well as their cumulative anxiety score from all of the annual surveys.

Patients with high cumulative levels of anxiety were 6% more likely to die or have a nonfatal heart attack during the follow-up period, compared to those with low cumulative levels of anxiety.

What mattered most was whether the patients became more anxious over the years or calmer as time passed. That is, the patients' initial anxiety score wasn't a good predictor of their risk of death or heart attack. Their risk rose or fell in sync with their anxiety scores across the surveys.

The findings held in light of other risk factors, including age, sex, high blood pressure, diabetes, BMI (body mass index), education level, marital status, smoking, and total cholesterol.

However, the researchers say it's possible that other, unmeasured factors affected the results.

Future studies should test anxiety-reduction techniques in heart disease patients, note Blatt and colleagues.

SOURCE: Shibeshi, W. Journal of the American College of Cardiology, May 22, 2007; vol 49: pp 2021-2027.

Summary and analysis by Gil Gradisar, President, PrevaHealth

Italian Study Shows CT Colonoscopy Offers npv of 96.3%

COLORECTAL CANCER (CRC) is the most common cause of cancer-related death in non-smoking Americans and the second most common cause of cancer-related deaths in smokers (behind lung cancer). The American Cancer Society estimates that this year there will be about 99,200 new cases and 48,100 deaths from colon cancer and 37,200 new cases and 8,600 deaths from rectal cancer.

Computed tomographic (CT) Colonography has been shown to be sufficiently accurate in detecting colorectal neoplasia. Less invasive and better tolerated than colonoscopy, CT Colonography is now considered a valid alternative for CRC screening in the general population and is now recommended by the American Cancer Society as a preferred front-line screening test in average risk individuals. However, less information is available on its performance in individuals at increased risk of CRC. In the June 17, 2009 edition of the Journal of the American Medical Association is a study designed to assess the accuracy of CT colonography in detecting advanced colorectal neoplasia in asymptomatic individuals at increased risk of CRC using unblended colonoscopy as the reference standard.

Individuals with first-degree family history of advanced colorectal neoplasia, those who have had resection of colorectal adenomas, and those with positive results from fecal occult blood tests (FOBTs) are at increased risk of CRC. However, adherence to follow-up colonoscopy in these individuals is suboptimal. The aim of this study was to assess sensitivity and specificity of CT Colonography in detecting advanced neoplasia (ie, advanced adenoma or CRC) 6 mm or larger in individuals at increased risk of developing CRC, because of either family history of advanced colorectal neoplasia in first-degree relatives, personal history of adenomas, or positive results from immunochemical FOBTs.

This was a multicenter, cross-sectional study. Individuals at increased risk of CRC due to either family history of advanced neoplasia in first-degree relatives, personal history of colorectal adenomas, or positive results from fecal occult blood tests (FOBTs) were recruited in 11 Italian centers and 1 Belgian center. Each participant underwent CT colonography followed by same-day colonoscopy.

Of 1103 participants, 937 were included in the final analysis: 373 cases in the family-history group, 343 in the group with personal history of adenomas, and 221 in the FOBT-positive group. Overall, CT colonography identified 151 of 177 participants with advanced neoplasia 6 mm or larger and correctly classified results as negative for 667 of 760 participants without such lesions.

The positive and negative predictive values were 61.9% and 96.3%, respectively; after group stratification, a significantly lower negative predictive value was found for the FOBT-positive group.

Conclusions: In a group of persons at increased risk for CRC, CT colonography compared

with colonoscopy resulted in a negative predictive value of 96.3% overall. When limited to FOBT-positive persons, the negative predictive value was 84.9%.

Based on this most recent study, if VC has a NPV of 95% or greater for people who are at high risk (people who were not screened but for diagnosis) then for a screening population the NPV is closer to 99%. If your patient is a reluctant candidate for screening for colon cancer, CTC may be the answer.

J.A. Rumberger, M.D. FACC

Emerald Professional Building.5747 Perimeter Drive, Suite 105 Dublin, Ohio 43017 tel. (614) 652-5888 fax (614)652-5890 www.prevahealth.com

Medical Director, PrevaHealth

Protein Thought to Cause Heart Disease Doesn’t, Study Finds

C-reactive protein, or CRP, a marker of inflammation in the body, is unquestionably associated with heart disease and only a short time ago was thought to be more important than cholesterol in heart disease. Multiple studies found that the higher a persons CRP, the greater the likelihood of heart disease. A widely publicized study released last year suggested that even people with low cholesterol could protect themselves from heart attacks if they took a statin, a cholesterol-lowering drug that also lowers CRP levels.

But in a paper to be published Wednesday in The Journal of the American Medical Association, researchers analyzing genetic data from more than 100,000 people conclude that their study “argues against” the notion that the protein causes heart disease. Dr. David Altshuler, a professor of at Harvard Medical School, said the distinction was important. If CRP caused heart disease, lowering it would protect people. But if it was merely associated with the disease, lowering CRP would have no more effect on health than stopping a fire alarm would have on putting out a fire.

The new study, by Dr. Paul Elliott of Imperial College in London and 35 co-authors, made use of a recently developed technique that can get answers quickly about causality. Without it, the only method was what is seen as the gold standard in medicine — large controlled clinical trials in which people are randomly assigned to take a drug, or not, and followed for years. The new method, Mendelian randomization, “is changing the way we think about causality,” Dr. Lauer said. It is a type of study that recently became feasible as researchers found genetic variants associated with proteins like CRP and developed tools to analyze data from what was, in this case, more than 100,000 people.

Different people produce different amounts of CRP, and the amount a person produces is determined by inherited changes in the CRP gene. So in a population, there are people who just happen to produce more CRP throughout their lives and others who just happen to produce less. If CRP causes heart disease, those who make more CRP would have more heart disease. That, however, is not what the study found.

“There was no association” between CRP genes and heart disease rates, Dr. Elliott said. People with genes that increased CRP production throughout life had no more heart disease than those with genes resulting in less CRP. The association between CRP and heart disease must be reflecting something else. For example, if CRP levels go up when heart disease begins, because there is inflammation in the arteries, CRP levels would be higher in people with incipient heart disease. But CRP itself would be playing no role in heart disease risk — it was just marker of inflammation in the arteries.

It is still not clear whether doctors should routinely add CRP tests to their arsenal. The test is not now recommended but a constituency of cardiologists argued that it should be.” Guideline writers are now chomping on this,” said Dr. Steven Nissen, of the Cleveland Clinic. “New guidelines are coming out this year, and the commission is probably struggling about what to say.”

While the quest for a blood test for CVD goes on, here in Central Ohio we have the most accurate non-invasive test for the earliest detection of CVD, the EBT heartscan. Our data and recommendations help you guide your patients care accurately with evidence-based recommendations.

J.A. Rumberger, M.D. FACC

Medical Director, PrevaHealth

Screening for Sleep Apnea

Should screening for sleep apnea be required for all men? Studies suggest that men aged 20 to 29 with severe sleep apnea have 10 times the risk of dying from heart related ailments than their non sleep apnea peers in the general population, and a much higher risk than older men with sleep apnea. . The study, which appears in the March 2005 European Respiratory Journal, was based on the largest population of sleep apnea patients (nearly 15,000 men) ever to be studied also showed that men aged 30 to 39 have three times the risk of dying, while those in their forties have twice the risk. But those aged 50 or older don't have a higher risk of dying than the same age group in the general population.

"We were surprised to find a sharp decline in the risk of dying after age 50," says lead researcher Professor Peretz Lavie of the Lloyd Rigler Sleep Apnea Research Laboratory at the Technion-Israel Institute of Technology. "Older patients have more risk factors, especially cardiac ones, so we expected relative mortality to increase with age," he notes. "The fact that they don't suggests that patients with sleep apnea develop a mechanism, as yet unknown, that protects their cardiovascular system."

In light of these findings, Lavie recommends a change in sleep apnea testing guidelines. Currently, patients seek help only when their symptoms become noticeable and disturbing, and the average age of sleep clinic patients is around 50. Lavie believes screening should be conducted not only for twenty somethings with sleep apnea symptoms, but also for other groups known to have a high prevalence of sleep apnea -- even if they do not have characteristic symptoms. These include the young obese, people who developed hypertension at a young age or children of sleep apnea sufferers. Diagnosing and treating sleep apnea at an early age, he says, would lower fatalities. He is careful to point out that sleep apnea patients who are older than 50 should still be treated, to improve their condition and quality of life, and reduce the risks of automobile and work-related accidents.

Sleep apnea is characterized by interruptions in breathing during sleep that last 10 seconds or more, at least five times per hour. They cause repeated interruptions of sleep and decreased oxygen levels in the blood, and have been linked with cardiovascular diseases, especially hypertension. The condition affects up to 10 percent of adult men, who in most cases are not aware that their breathing stops during sleep but who complain of chronic fatigue, excessive sleepiness, tendency to doze off during the day and loud, intermittent snoring.

“This study reinforces the fact that sleep apnea patients represent a vulnerable population that would especially benefit from a heartscan or full vascular analysis to assess their cardiovascular risk as a complication of their disease.” J.A. Rumberger, M.D. FACC-Medical Director, PrevaHealth

Stocking a Heart-Healthy Kitchen

Certain foods contribute to a heart-healthy diet. From fruits and vegetables to whole grains, these are the foods that you should keep on hand.

Fresh Fruits & Vegetables

Fill your fridge with seasonal fruits such as berries, oranges, apples, pears, and grapes, and vegetables such as bell peppers, broccoli, kale, cauliflower, tomatoes, dark leafy greens, celery, eggplant, zucchini, and squash.

Dairy and Dairy Alternatives

• Skim or 1% milk
• Soymilk (plain, unsweetened, vanilla, or chocolate)
• Low - or nonfat buttermilk
• Nonfat half-and-half or nonfat creamers
• Nonfat or reduced-fat cheese (bricks, slices, or shredded)
• Soy-based cheeses (bricks, slices, or shredded)
• Nonfat or light cream cheese
• Nonfat or 1% fat cottage cheese or ricotta cheese
• Nonfat or 1% fat yogurt (includes fruited, vanilla, or plain)
• Soy-based yogurts
• Nonfat sour cream
• Egg substitutes, egg whites

Meat, Poultry, Fish & Meat Substitutes

• Skinless, boneless chicken or turkey breasts and tenders
• Skinless, white breast meat ground chicken or turkey
• Pork tenderloin, trimmed of fat
• Lean ground beef such as ground round or ground sirloin (Note: When buying beef, look for words like "round" or "loin" and choose lean cuts to lower the fat content.)
• Assorted fish: salmon, mackerel, tilapia, trout, herring, tuna
• Tofu silken, soft, firm, or extra firm

Frozen Foods

• Frozen vegetables and vegetable blends without added sauces, gravies, etc
• Frozen fruits without added sugar (frozen blueberries, strawberries, or raspberries)
• Frozen soybeans (edamame)
• Frozen vegetarian burgers, sausage patties, or links (Boca Burgers, Yves, Morningstar Farms or Gardenburger)
• Reduced-fat and sodium vegetarian chili, burritos, and entrees like Amy's Organic and Health Valley.

Fats, Cooking Oils

• Assorted cooking oils (olive, canola, walnut, grapeseed, peanut, and sesame)
• Non-fat cooking sprays (for example, Spectrum Naturals, Pam)
• Baking fat replacements (for example, pureed prunes, applesauce, or Smucker's Baking Healthy)
• Non-hydrogenated shortening (for example, Spectrum Naturals)
• Trans-free liquid or tub margarine (for example, Promise Activ, Benecol, Fleischmann's Light, Smart Balance)
• Reduced-fat or nonfat salad dressings
• Herbs, Seasonings & Spices
• Use herbs and natural seasonings to take the place of salt.

Sweeteners

• Splenda, Equal, Nutra Sweet, Sugar Twin, and Brown Sugar Twin (sugar substitutes)
• Sugar free or "light" maple syrups
• Honey
• Brown rice syrup for a sweetening alternative to use when baking

Pantry Essentials

Snacks

• Assorted raw nuts and seeds (almonds, walnuts, sunflower seeds, sesame seeds)
• Dried fruits
• Whole-grain breads, tortillas, pitas
• Whole-grain, trans-fat free crackers (such as Health Valley whole wheat crackers, Kashi TLC crackers, Reduced Fat Triscuits, Fat Free Rye Crisp, Wasa)
• Baked, trans-fat-free tortilla chips
• Brown rice cakes, popcorn cakes
• Whole-grain pretzels (such as Snyder's oat bran or honey wheat)
• Plain popcorn or light microwave popcorn

Condiments

• Assorted vinegars: rice, red wine, balsamic, apple cider, raspberry as salad dressings.
• Reduced-sodium ketchup
• Assorted mustards: whole grain, honey, Dijon, yellow
• Reduced-sodium soy sauce
• Reduced-fat or nonfat mayonnaise
• Barbecue sauce

Beans, Grains, Sauces

• Assorted canned beans such as lentils, kidney, garbanzo, pinto, and black beans
• Dried beans (lentils, split peas, garbanzo beans, black beans)
• Reduced-sodium soups with beans (for example, Health Valley)
• Vegetarian chili beans (for example, Westbrae Naturals or Health Valley)
• Vegetarian or nonfat refried beans
• Rolled, steel cut, or Irish oats
• Oat bran
• Whole or ground flaxseeds
• Whole-grain cereals (Look for 5+ grams of dietary fiber and less than 8 grams of sugar per serving.)
• Barley
• Brown rice, wild rice, and brown basmati rice
• Grains such as wheat berries, couscous, polenta, millet, bulgur or quinoa
• Whole-wheat, spelt, or kamut pastas (Note: These whole-grain pastas come manyi varieties.)
• Wheat germ
• Whole-wheat flour and whole-wheat pastry flour
• Soy flour
• Cornmeal
• Reduced-sodium canned diced tomatoes, whole tomatoes, and tomato sauce
• Low-fat or fat-free pasta sauce
• Reduced-sodium chicken, beef, and vegetable broths
• 98% fat-free cream of mushroom or chicken soups (for example, Campbell's Healthy Request)