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Tuesday 22 March 2016

How High Is Too High for Triglycerides and Cardiovascular Risk?

TEL-HASHOMER, ISRAEL — In patients with coronary heart disease, even triglyceride levels on the high side of normal (100 to 149 mg/dL) are associated with an increased risk of death, new research shows[1].

"The current threshold for the definition of elevated triglycerides levels for patients with CHD may be higher than desired," Dr Robert Klempfner (Sheba Medical Center, Tel-Hashomer, Israel) and colleagues write in their study, published online March 8, 2016 in Circulation: Cardiovascular Quality and Outcomes.

To clarify the association between different triglyceride levels and long-term all-cause mortality, the authors evaluated 22-year mortality data on 15,355 patients with proven CHD who were screened between 1990 and 1992 for the Bezafibrate Infarction Prevention (BIP) trial, a secondary-prevention trial.

Patients were divided into five groups based on fasting serum triglyceride levels at screening: low-normal triglycerides (<100 mg/dL), high-normal triglycerides (100–149 mg/dL), borderline hypertriglyceridemia (150–199 mg/dL), moderate hypertriglyceridemia (200–499 mg/dL), and severe hypertriglyceridemia (>500 mg/dL).

Most patients were men (81%) and had a history of a previous MI (72%). Notably, more than 90% of patients had received no lipid-modifying medication.

Age- and sex-adjusted survival was 41% in the low-normal triglyceride group vs 37%, 36%, 35% and 25% in groups with progressively higher concentrations of triglycerides (P<0.001), according to the authors.

When the investigators assessed triglycerides as a continuous measure, each unit of natural logarithm triglycerides elevation was independently associated with a 26% increase in all-cause mortality adjusted for age and sex only. This association remained significant after adding HDL-C to the model (HR 1.12; 95% CI 1.06–1.18), they report.

Shorter follow-up from the BIP registry also found a stepwise increase in age-adjusted 5-year mortality with increasing triglycerides, but the association was not statistically significant after adjustment for HDL-C and other covariates.

The parent study reported a nonsignificant 9.4% reduction in fatal and nonfatal MI or sudden death with the fibrate drug bezafibrate[2]

"An interesting lesson could be derived from the BIP study: despite a significant HDL-C increase in the bezafibrate treatment arm, the overall benefits were nonsignificant. However, the benefit of bezafibrate in the subgroup of patients with high triglyceride levels was impressive," Klempfner writes. "In all the available five randomized control trials, the beneficial effects of fibrates were highly significant in patients with hypertriglyceridemia."

The study was limited by the inability to adjust for potential confounders such as morbidity and treatment given and the lack of information on cause of death, he notes. Mortality data were obtained by matching patients' identification numbers with their vital status in the National Population Registry.

The authors presumed the deaths were cardiovascular because higher triglyceride levels remained independently associated with all-cause mortality after excluding patients who developed incidental cancers. Further, 8-year follow-up data in randomized BIP patients showed that about 58% of deaths were due to a cardiovascular cause, they note.

This assumption seems to be valid but remains a limitation nonetheless, Drs Karol Watson and Dr Philipp Wiesner (University of California, Los Angeles, CA) write in an accompanying editorial[3].

Other limitations that temper enthusiasm include the lack of follow-up lipid values, follow-up medication use, and ascertainment of important comorbidities, such as diabetes.

Still, the study, with its large numbers of patients and long follow-up, provides useful information and takes on "special importance given that elevations in triglycerides are increasingly common in current-day society," the editorialists write.

National Health and Nutrition Examination Survey (NHANES) data from 1988 to 2010 reveal that 47% of Americans had triglyceride levels >150 mg/dL and 1% had levels >500 mg/dL.

Clinicians have debated for years how to tackle this problem. While lifestyle interventions remain an effective method, trials like ACCORD, AIM-HIGH, and HPS-2 have failed to show a benefit with adding agents, primarily targeting triglycerides, on top of statins.

Antisense apolipoprotein C-III inhibitors have been shown to be effective and safe in lowering triglycerides in early clinical trials, but whether these drugs will be able to improve cardiovascular outcomes remains to be seen.

"Although we search for the true significance of elevated triglycerides in cardiovascular risk and potentially the optimal method to lower triglycerides, we congratulate Klempfner et al on an important study, which provides support for the idea that triglycerides should be taken more seriously as a future target to improve patient outcomes," Watson and Wiesner write.

Low carb is the optimal way to lower Trigs.



Bob Bushell said...

Nice to kmow Jan.

Lowcarb team member said...

We aim to give a wide selection of articles.
Pleased that this article, posted by Graham, was of interest to you.
Many thanks for your comment, we are always pleased to receive, read and share them.

All the best Jan

Margaret D said...

At this stage I don't have to be concerned about that, but interesting read all the same.

Lowcarb team member said...

Many thanks for your comment.
Glad you found this article interesting ...

All the best Jan

chris c said...

And yet not a few GP surgeries no longer measure trigs, only total cholesterol and maybe HDL, to check for statin deficiency.

I reduced mine to 1/10 of what they were by low carbing (and doubled my HDL). Will that overcome the fifty years when they were high? Watch this space . . .

Lowcarb team member said...

chris c said...
And yet not a few GP surgeries no longer measure trigs, only total cholesterol and maybe HDL, to check for statin deficiency.

I reduced mine to 1/10 of what they were by low carbing (and doubled my HDL). Will that overcome the fifty years when they were high? Watch this space . . .

Yep my surgery only tests for HDL and TC, considering LDL was the bad guy for many years what's the rationale for disregarding, as LDL is the target of statins just what citeria do they use for starting them


chris c said...

If alive then prescribe statin


Think about it, if they spent the money on tests how could they afford the statins?

Strangely the lab my doctor used to use actually measured LDL- usually it is calculated and the calculation is thrown off by low trigs - currently the lab has gone back to calculated LDL probably because the kit is cheaper.

I suspect the rationale is that everyone will have high trigs if they eat high carb low fat, and if they don't they don't deserve treatment.

Lowcarb team member said...

Your lucky in a way Chris as you already know my cholesterol test is limited to total and HDL, seems that the criteria for statin prescribing has now shifted away from LDL at least as far as my surgery goes

chris c said...

I'm only lucky if I can get to see a doctor, the nurses use only TChol or TChol and HDL, and the receptionist wouldn't permit any tests at all. At one stage we could only see a doctor if the receptionist permitted it. Since PCTs went away they seem to have changed the Rules. Well changed them back, at one time the surgery was excellent, then it became rather less than mediocre. Obviously patient health was too expensive to bother with.

Well except for handing out statins like candy of course.