Rethinking the Risk of Low HDL

Despite plenty of evidence that people with low levels of “good”cholesterol are more prone to heart attacks, a large new study suggests that the lacking lipid is not to blame.

The analysis of data on nearly 70,000 people in Denmark affirmed the link between low levels of high-density lipoprotein (HDL), the so-called “good” cholesterol, and raised heart attack risk in the general population. But in people with a gene mutation that lowers HDL, heart attack risk was not found to be higher at all.

“Association itself doesn’t mean causality,” said lead author Dr. Ruth Frikke-Schmidt, a consultant in the Department of Clinical Biochemistry at Rigshospitalet in Copenhagen.

The results, published in the Journal of Clinical Endocrinology and Metabolism, indicate that just having low HDL is not what raises the likelihood of a heart attack.

“People with low ‘good’ cholesterol also have a whole bunch of other factors that relate to heart disease,” said Dr. Christopher Cannon, professor of medicine at Harvard Medical School and editor of the American College of Cardiology’s website.

It’s difficult to study and isolate “good” cholesterol, added Cannon, who was not involved in the new study. People with low HDL often suffer from obesity, high blood pressure and diabetes and sometimes have higher levels of LDL, or “bad” cholesterol, he said.

To try to isolate the effects of HDL itself, Frikke-Schmidt and her colleagues focused on people with a well-known variant of a gene called LCAT, which lowers HDL levels and occurs in about four percent of the population.

The variant gene is used as a stand-in for low HDL, she noted, but people with the variant don’t necessarily have the other risk factors that usually affect HDL levels in the larger population.

In the new study, a 13 percent decrease in HDL relative to average levels in the population was linked to an 18 percent increase in heart attack risk — if the low HDL was not explained by a gene variant. For people with the variant gene, the same HDL reduction was not linked to any increased risk of heart attack.

The findings fit in with Frikke-Schmidt’s earlier research showing that two other genetic variants that lower “good” cholesterol levels are not associated with an increased risk of heart disease.

According to both Frikke-Schmidt and Cannon, the debate is particularly important, because there are currently drugs in trials that would raise “good” cholesterol.

If low HDL is not a cause of heart attacks, raising HDL may not be protective, they point out.

Ruling out low levels of “good” cholesterol, Frikke-Schmidt said the most likely cause of the increased risk is so-called remnant lipoproteins, which are like “bad” cholesterol and carry fats through the blood.

Until the real mechanisms are sorted out, Cannon said it’s still important for people to try and raise their “good” cholesterol by exercising and losing weight.

“Beyond that there are so many question marks,” he said. “We’re kind of in a wait and see mode.”

SOURCE: The Journal of Clinical Endocrinology and Metabolism, online November 16, 2011.

Carbohydrates and Heart Disease

Clinically, I’ve seen consistent improvements in heart disease markers when implementing a low glycemic diet. The glycemic index is an indicator of how high the carbohydrate portion of a food causes blood sugar to rise-this is especially important for diabetic patients, but is also useful when trying to limit the effect of carbohydrates on the body. A new study published in the Archives of Internal Medicine found that eating lots of high-glycemic-index foods puts women at higher risk of developing heart disease. Some highlights from the study are as follows:

• Women with the highest carbohydrate intake were twice as likely to develop heart disease as women with the lowest intake.

• Only high-glycemic-index carbohydrates were associated with heart disease risk; low-glycemic-index carbohydrates were not.

• Having a high dietary glycemic load more than doubled the risk of heart disease in women.

• No relationship between heart disease and carbohydrate intake, high-glycemic index food consumption, or dietary glycemic load was seen in men.

The bottom line is that all carbohydrates aren’t created equal-paying close attention to the glycemic-index of foods, along with incorporating foods that help to keep the glycemic load down (nuts, beans, lentils, seeds), is a proven method of lowering your heart disease risk.

Cholesterol and Red Yeast Rice

High cholesterol should often be considered an indicator of excess oxidation, inflammation, and other underlying factors. However, despite the appropriate lifestyle changes, genetics often stand in the way of achieving optimal cholesterol levels. In these instances, supplements such as red yeast rice may prove beneficial:

Red Yeast Rice Extract Lowers M.I. Incidence and Mortality from Coronary Disease

Author: Steve Austin, N.D.

Reference: Li J-J, Lu Z-L, Kou W-R, et al. Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). J Clin Pharmacol 2009;49:947-56.

Design: Randomized double-blind intervention trial

Participants: 1530 elderly (≥65 years of age) hypertensive subjects with a history of myocardial infarction (MI)

Study Medication and Dosage: Subjects received either Xuezhikang, a red yeast rice (RYR) extract, administered as 600 mg b.i.d., or placebo for an average of 4.5 years. Each 600 mg capsule of RYR contained 2.5-3.2 mg of monacolin K plus “a small quantity of lovastatin hydroxyl acid as well as ergosterol and some other components.”

Primary Outcome Measures: Recurrent coronary events

Key Findings: Compared with the placebo group, there was a 38% reduced risk of suffering a coronary event (primarily MIs) (P=0.0009). Similarly there was a 29% reduced risk of dying from coronary disease during the course of the trial (P=0.05). Secondary endpoints revealed a 21% decline in LDL levels in the RYR group (P=0.0001) and a 12% decline in triglyceride levels (P=0.003) compared with trivial declines in the placebo group. Total mortality also declined by 36% in the group receiving RYR (P=0.003).

Practice Implications: RYR extracts are known to reduce cholesterol levels in humans and have been traditionally used in China to treat people with cardiovascular disease. RYR naturally contains the same molecule found in the prescription drug lovastatin. Previous RYR research has focused primarily on cholesterol reduction, though some evidenc
e for reduction in inflammatory markers has also surfaced.

The current trial goes several steps further, showing clinically (and statistically) significant reductions in coronary disease incidence and mortality. Hidden in the data is a near-statistically significant (P=0.06) 37% reduction in the risk of stroke and a statistically significant (P<0.04) reduction in total cancer incidence when compared with the placebo group. No current understanding of the effects of RYR clearly explains these additional positive findings.

One caveat requires mentioning: a previous report studying the pharmacokinetics of a related statin drug found that area-under-the-curve response was twice as great in Chinese subjects compared with white subjects (Clin Pharmacol Ther 2005;78:330-41). Should further investigations confirm these findings in regard to monacolins found in RYR, white (and potentially black) patients might require significantly higher doses of RYR to achieve the same clinical outcomes that occurred in the new report, which studied Chinese subjects.