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“According to the tests I’m afraid your BAD cholesterol has corrupted your GOOD cholesterol!” the doctor with clipboard in hand told the cartoon character Ziggy.                                                 ©2014 Ziggy and Friends, Inc.

“It is important for clinicians to continue to consider the entire spectrum of coronary heart disease risk factors, and not assume that a very high HDL-C is automatically or fully protective against CHD.”                              John T. Wilkins, MD, MS, et al, Journal of the American Heart Association, March 13, 2014

More HDL Cholesterol Is Better—Unless it’s the Wrong Kind or Other Risk Factors Are Present

It is believed that more HDL “good” cholesterol means cleaner, healthier, less inflamed arteries; the more the better. If that sounds too good to be true, it may be. “[HDL] turns out to be so much more complicated than we thought,” Cleveland Clinic cardiologist Stanley Hazen told reporters. A recent study found that “good” cholesterol can in some cases be bad. Another study determined that very high levels of HDL cholesterol can provide a false sense of security.

The “bad” HDL cholesterol finding illustrates the problem.

Harvard researchers Frank M. Sacks, MD, Majken K. Jensen, PhD, and colleagues found two forms of HDL cholesterol: the major subclass which is, in fact, good for the heart and a small subclass (~13%) which appears to be harmful. The study was first published online April 12, 2012, in the Journal of the American Heart Association.

Specifically, HDL cholesterol carrying a small protein called apolipoprotein C-lll (apoC-lll) appears to increase the risk of coronary heart disease (CHD). Without apoC-lll, HDL cholesterol seems to be especially heart protective. The minor subclass is pro-inflammatory and the major subclass is anti-inflammatory. As you will see, inflammation level is a key factor in risk assessment. (ApoC-lll also resides on LDL “bad” cholesterol.)

The relative risk per standard deviation of HDL-C without apoC-lll was found to be 34% less, while the risk for HDL-C with apoC-lll was shown to be 18% more. Put another way, the men and women who had HDL with apoC-lll in the highest 20% of the population had a 60% increased risk of heart disease.

These findings were arrived at by comparing blood samples of initially healthy subjects who developed CHD during a 10 to 14 year follow up with samples from similarly situated subjects who did not develop CHD. Blood samples from 18,225 men and 32,826 women were examined; 634 developed CHD during the follow-up period. The results were adjusted to eliminate the confounding effects of factors such as age, smoking, diet, and lifestyle.

Jensen et al concluded: “Separating HDL-C according to apoC-lll identified two types of HDL with opposing associations with risk of CHD. The [heart disease] effects of apoC-lll, as a component of…LDL, may extent to HDL.” LDL is, of course, the “bad” cholesterol.

This finding promises to significantly improve the precision of risk assessment. Near term, however, the effect is to cloud the prognostic power of total HDL cholesterol.

Sachs, a professor of cardiovascular disease prevention, told reporters: “This finding, if confirmed in ongoing studies, could lead to better evaluation of risk of heart disease in individuals and to more precise targeting of treatment to raise the protective HDL or lower the unfavorable HDL with apoC-lll.”

Sacks and his team suggest that blood tests be expanded to measure HDL with and without apoC-lll. “Reduction in HDL- apoC-lll by diet or drug treatment may become an indicator of efficacy,” Sacks added.

Now, let’s turn to a study of men and women with very high levels of HDL cholesterol. It helps to put my own reading into perspective. Led by John T. Wilkins, MD, Department of Preventive Medicine, Northwestern University, the study was published March 13, 2014, in the Journal of the American Heart Association.

Plateau Effect for Very High HDL Cholesterol

Using pooled data from six studies totaling 307,245 person years of follow-up, Wilkins and colleagues examined coronary heart disease (CHD) events and mortality across a broad range of HDL cholesterol, including levels over 80 mg/dl. The very large data base provided a unique opportunity to study CHD risk in those with extreme elevations of HDL cholesterol. The researchers hypothesized that CHD risk would become less predictable in individuals with very high levels of HDL-C when compared with more normal values of 45- and 55-mg/dl for men and women, respectively. That’s essentially what they found. Very high HDL-C was not always better.

“Although CHD event rates were generally lower in cohort participants with very high HDL-C, risk for CHD events persisted in this group as many participants with very high HDL-C still experienced [heart attack] or CHD death during follow-up,” the researchers wrote.  

In men, heart disease events went down as HDL-C went up in a direct fashion, but only up to a point. At HDL levels above 90, the pattern of association plateaued. The same pattern was found for women, but risk reduction topped out at HDL values above 75. Importantly, mortality rates increased for men in the highest and lowest HDL categories; when adjusted for traditional risk factors, however, death rates for men with very high HDL cholesterol were substantially reduced.

Revealingly, men and women who had heart disease events in spite of very high HDL-C were also found to have an increase in traditional risk factors such as high blood pressure, non-HDL cholesterol, and age.

“[This suggests] that at-risk individuals with very high HDL-C are at least partially identifiable through assessment of traditional risk factors,” Wilkins et al wrote.

The take away is clear. We should not be lulled into a sense complacency by very high levels of HDL cholesterol. “It is important for clinicians to continue to consider the entire spectrum of coronary heart disease risk factors, and not assume that a very high HDL-C is automatically or fully protective against CHD.” Dr. Wilkins and his colleagues counseled.

*  *  *

Lynn McFarlin, my doctor at the Cooper Clinic in Dallas, concurs that we cannot assume that my very high HDL-C is fully protective against heart disease. That’s why we continue to monitor all of my blood lipids and many other CHD risk factors. He noted that the low level of inflammation in my blood, as shown by my rsCRP reading, is encouraging. High inflammation, he explained, often sets off a cascade of harmful cardiovascular events in the body. He also recommends that we repeat a CT angiogram during my next evaluation. My last CTA showed my coronary arteries to be wide open and we want to keep it that way. For more details, see http://www.cbass.com/CTAHEART.htm

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