I am an Emergency Medicine Physician and wanted to make a comment/pose some questions that relate to my personal medical situation.  I have coronary artery disease in spite of the fact that I have no significant family history, never smoked, have never been over weight, have never been hypertensive, had excellent total cholesterol and trigliceride and acceptable LDL numbers, and have been an athlete/exerciser the majority of my life, including the recent 25 years.  However, my HDL was in the low to mid 30's.  Niaspan, 1500-2000 mg per day, raised it to the low to mid 60's, where it has been for at least seven years now.  I have never had a cardiac event or even significant chest pain or shortness of breath, but, being exquisitely tuned to my body's reactions, knew that at my highest levels of exercise, in excess of 900 calories per hour on a treadmill, "something" was not right.  I was worked up and found to have a right coronary artery 95+% obstruction and stented.  Thirteen years later, at the age of 63, similar occurred and, the original stent still being open, I was found to have a significant obstruction just proximal to that stent, and required further stenting, with an endeavor drug-elluding stent, in June of 2008.  Unfortunately, in spite of no change in my exercise abilities and no development of symptoms, 1 1/2 years after this latter procedure, I was found to have the new stents completely obstructed, but with excellent collaterals.  Of note is that I never missed a single dose of Aspirin or Plavix post endeavor stenting, nor have I ever missed any of my other medications, which include Pravachol, Niaspan, Toprol, and Altace.  I also take multivitamins with high levels of numerous substances, including the various Vitamin B's and Fish Oil.  My homocysteine level is not elevated.  When my June, 2008 stents were found to be fully obstructed 1 1/2 years later, the interventionalist, (world-renouned in the one of the major institutions in New York City), commented to the effect that obviously I'm just the type of person who closes them off, although I had never closed off my original bare metal stent that was placed in 1995.  In my practice in Emergency Medicine, as well as from being the son of a long-lived athlete (my mother lived almost 97 years and was very active), I know from my patients and from my mother that I've been struck with the fact that it seems a very large number of patients who reach 90 years of age, with no significant cardiovascular events, seem to have extremely high HDLs.  By that I mean, not the hoped-for 60's, like I have achieved, but 80's and 90's!  I suspect that those who endogenously have high HDL and, unlike myself, do not need therapy, such as my Niaspan, to achieve those favorable numbers, are also doing something else that we have not yet discovered that goes hand-in-hand with the high HDL production and is not addressed by drug therapy, such as Niaspan.  What are your thoughts on this?

Robert Werblin, M.D.

rwerblin@nycap.rr.com 

Dear Robert-

Thanks for your comment and for listening to our chat.  There is a great deal that we do not know about the function(s) of HDL.  We know HDL is involved in reverse cholesterol transport, but also has anti-oxidant, anti-inflammatory, anti-thrombotic and other properties that may affect atherosclerosis.   I suspect that individuals with life-long high HDL-C are different than those who develop high HDL-C due to medications.  They may be genetically different, have different associations with disease states, and have different pathophysiology related to their vascular health.  These may or may not be reflected in their HDL-C levels.  It is clear that there is more the HDL than HDL-C (i.e., more to the particle than how much cholesterol it carries).  Best regards - Jim

Bob,

This was a great program.  Unfortunately I’m afraid when the final publication is presented at AHA it will continue to leave many questions on the table.  When I look at the CDP population who had average TC’s of 250 and TG’s of 530 mg/dL (VLDL would have been over 100 mg/dL) and I look at the FATS population LDLc 194 mg/dL, HDLc 39 mg/dL and TG’s 210 mg/dL (NHDLc over 230 and VLDL over 40 mg/dL), we are in a different era of lipid risk management.  4S baseline LDLc was 190, HHS enrolled people with LDLc/HDLc ratios over 5 (yes LDLc/HDLc over 5)).  VAHIT – VLDLc was higher than HDLc values and treatment resulted in 30% reduction in TG’s (30% reduction in VLDL) – NHDLc again would have been higher risk.

While this study was intended to test the ‘HDL/TG hypothesis’ as written in the demographic publication - I do believe it really tested the LDL hypothesis once again and both treatments revealed similar outcomes.  As mentioned, HDL epidemiologic data shows 3 fold higher risk when comparing values below 40 mg/dL and values above 60 mg/dL.   This data was from an era where TC, NHDLc, LDLc and TG’s were quite high.  

In AIMHIGH the congruence of lipid values was also quite shocking:  NHDLc ~ 100, LDLc ~ 70 and ApoB ~ 80.  Pretty impressive starting points and both treatments showed further reductions.

Looking at the demographic data I think there were many confounders which will complicate results:

1.        Legacy effects of niacin users prior to washout/enrollment

2.       Much higher addition of ezetimibe above protocol expectations and design

3.       20% smoking population in a very high risk athero population

4.       BP mean 128/74 mm Hg in a ‘brittle’ vascular population

5.       ADPI therapy (was it enough)

6.       A1c 6.69% in a ‘brittle’ vascular diabetic population

7.       Sulfonylurea use and risk of hypo and weight gain

8.       Insulin use and risk of hypo and weight gain

9.       Certain antihypertensive therapy and risks (eg.  Atenolol, hctz) Orthostasis risk?

10.   Use of as much as 80 mg simvastatin (potent cyp3a4 agent and drug drug interactions)

11.   Placebo arm receiving 100-200 mg niacin

12.   Rise in HDL in both groups

13.   NSAID use and risk associated with such

14.   History of unknown peptic ulcer disease, anemia

15.   Lpa mass low 30’s may have been a risk factor in the old days of high TC, TG, LDLc, NHDLc but would be considered only high risk today in Europe with values over 50 nmol/L and over 70 nmol/L in the United States.

16.   Despite low HDLc, the ApoA1 was surprisingly high over 120 mg/dL

17.   LDLc/HDLc ratio of 2 and on therapy both arms dropped closer to 1.5 or less.  This would be a very low risk lipoprotein population reaching physiologic birth LDLc/HDLc values.

18.   Despite all this and the fact event rates were less than expected – the annual primary event rates were still quite high.    We must find an answer for this.

19.   Would we be better off identifying the very high risk population earlier in their disease course and implementing risk altering therapies?

20.   I think with the failure of LDLp/HDLp ratios in MESA as compared to TC/HDL ratios we will not find further answers when that analysis is completed.  As with many prior studies we will be forced to look at small subset analysis for further elucidation of risk/benefit.

21.   Finally, I complement PI’s and all who participated.  Lipid related risk was likely very low in this aggressively treated population.

I have no history of coronary artery disease. My father died of an MI. I am taking Lipitor 20 mg daily. Amand taking it for prophylaxis.

Cholesterol 127

HDL 33

LDL 75

triglycerides 138

With the above values, how concerned should I be regarding the low HDL. 

thank you, Paul