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."