Just Read: Triglycerides and Cardiovascular Disease – American Heart Association Scientific Statement

Yes, all 40+ pages of the American Heart Association’s scientific statement, published in 2011 (the most recent one – citation below), for leisure.

Why?

Triglycerides are that lipid component in our blood that we (or let’s say I) are trained not to pay that much attention to, especially relative to cholesterol (LDL, HDL, etc), and yet its story unlocks a lot of mysteries around nutrition and health (again, for me).

Jumping right in.

  • “It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).”
    • As much as we’re fighting LDL, we don’t seem to be winning on this one. Why? And does it matter? (several reasons, and yes)

The dyslipidemic triad and diabetes

High triglyceride levels that accompany either normal or impaired fasting glucose predict the development of Type 2 Diabetes,1and therefore, hypertriglyceridemic states should prompt surveillance to rule out T2DM. In addition, 35% of T2DM adults have fasting triglyceride levels > 200 mg/dL associated with decreased HDL-C and small, dense LDL particles.

Size matters – of LDL particles, that is

LDL particles in patients with DM may be atherogenic even at normal LDL-C concentrations..In addition, hypertriglyceridemia is associated with small, dense, and CE-depleted LDL particles. Thus, individuals with T2DM and mild to moderate hypertriglyceridemia exhibit the pattern B profile of LDL (smaller, denser particles) described by Austin and Krauss; these particles be more susceptible to oxidative modification and catabolism via macrophage scavenger receptors

That’s the not good thing that happens inside blood vessels that causes disease and it’s connected to triglycerides.

In other words (my interpretation), it’s not what triglycerides mean by themselves, it’s the pattern that they are connected to. And therefore, looking at just one number (LDL) has limitations to predict disease. On the other hand, focusing on LDL is easy to do and simple to understand…hence the need for this scientific statement to understand the biology better than most people probably do.

Continuing on.

How we got here. The low-fat diet aka SnackWells USA

The relationship between percent of total fat intake and change in triglyceride and HDL-C concentrations was reported in a meta-analysis of 19 studies published by the Institute of Medicine. In this analysis comparing low-fat, high-CHO diets versus higher-fat diets, for every 5% decrease in total fat, triglyceride level was predicted to increase by 6% and HDL-C to decrease by 2.2%

Overall, optimization of nutrition-related practices can result in a marked triglyceride-lowering effect that ranges between 20% and 50%. These practices include weight loss, reducing simple CHO at the expense of increasing dietary fiber, eliminating industrial-produced trans fatty acids, restricting fructose and SFA, implementing a Mediterranean-style diet, and consuming marine-derived omega-3 PUFA (Table 11). Dietary practices or factors that are associated with elevated triglyceride levels include excess body weight, especially visceral adiposity; simple CHOs, including added sugars and fructose; a high glycemic load; and alcohol.

And the American Heart Association recommended high carbohydrate diets and even candy in the prevention of cardiovascular disease. Oops.

For the biologists/scientists – how carbohydrates may result in higher triglycleride levels and unhealthy lipid profiles

Mechanistically, high CHO intake triggers pancreatic insulin release in response to increased blood glucose. Insulin, in turn, activates sterol regulatory element–binding protein, (SREBP-1c), a transcription factor that regulates fatty acid and triglyceride synthesis. Recently, 2 additional transcription factors, X-box binding protein 1 (XBP1) and CHO response element–binding protein (ChREBP), have been identified as inducers of hepatic lipogenesis in response to ingested CHOs (eg, fructose and glucose) that is independent of insulin.431,432 In contrast, unsaturated fatty acids reduce or inhibit SREBP-1c transcription, thereby reducing hepatic fatty acid synthesis430 and plasma triglycerides.

Using drugs to treat

However, in LIPID, although baseline triglyceride level was not signifi- cantly associated with CVD risk in patients given placebo, each 89-mg/dL decrease in on-treatment triglyceride level in patients given pravastatin significantly decreased CVD risk by 11%, as well as by 14% after adjustment for nonlipid risk factors. However, the lipid-related parameters most strongly associated with CVD risk in LIPID were apo B, LDL-C, and the ratio of TC to HDL-C

Again, the dyslipidemic triad.

Taken together, reductions of 50% or more in triglyceride levels may be attained through intensive therapeutic lifestyle change.

A low fat, high carbohydrate diet increases triglycerides and decreases HDL, the opposite, a higher fat, lower carbohydrate diet reduces triglycerides and increases HDL. For me this explains the non-sequitir of my pathology textbook in medical school stating that high carbohydrate diets are a risk factor for heart disease at the same time high carbohydrate diets were being recommended to prevent heart disease.

A discussion of statins is out of scope here – many many many, many many, articles already cover this.

Andrew Weil, MD’s advice to us in medical school – understand what you’re prescribing to your patients

…I think he may have said that we should try every drug we prescribe to understand its effects (with rationality of course) but human memory can be semi-faulty after so many years…either way it was something of a gift for him to be on faculty at my medical school (University of Arizona) because it promoted an embrace of curiosity that persists to this day, every day.

In any event, I’ve switched to a low carbohydrate diet over the past year. I’m not ready to share my personal health information here, but I will eventually. And my biology is tracking science, as expected, because, well, that’s how science works :).

More to come. In the meantime, here’s a helpful piece on the low-fat diet and what it has done for our health.

Citation: Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and Cardiovascular Disease. Circulation [Internet]. 2011 [cited 2016 Dec 25];123(20).

Ted Eytan, MD