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Triglycerides and Residual Atherosclerosis Risk
Quick Takes
- The study conclusions are based on indirect evidence, but add to the growing literature that triglycerides are at the least a risk marker and likely risk enhancer for atherosclerotic cardiovascular disease (ASCVD) even in low-risk persons who are not diabetic.
- The European SCORE 10-year estimate was very low, but estimates CV deaths, not ASCVD events, as does the ASCVD Risk Estimator Plus in the United States. But using mean data for men in this study, the estimated 10-year risk of ASCVD events was <2%.
- The tool to associate triglycerides with atherosclerotic plaque was sought by ultrasound in noncoronary vessels whose luminal diameter is 2- to 10-fold the coronary bed and intracranial vessels. This reduces the ability to translate the results to all vascular beds, particularly in relationship to CV events.
Study Questions:
Are triglyceride (TG) levels associated with subclinical atherosclerosis and vascular inflammation in apparently healthy persons regardless of low-density lipoprotein cholesterol (LDL-C)?
Methods:
This observational, prospective cohort study was conducted in Spain in 3,754 middle-aged men and women with low to moderate cardiovascular (CV) risk participating in the PESA (Progression of Early Subclinical Atherosclerosis) study recruited between 2010 and 2014. Atherosclerotic plaques were assessed by 2-D vascular ultrasound in the carotids, infrarenal aorta, and bilateral iliac and femoral arteries. Coronary artery calcification (CAC) was assessed by noncontrast computed tomography. Vascular inflammation in the same peripheral vascular beds was assessed by F-18 fluorodeoxyglucose uptake by positron emission tomography (PET) in 614 who had evidence of plaque by 2-D ultrasound and were not on statins. Cardiovascular risk factors were assessed. Risk was defined using the Systematic Coronary Risk Evaluation (SCORE), in which the 10-year risk of CV death is divided into low (<1%), moderate (≥1% and <5%), or high risk (≥5%) who were excluded. Hypertriglyceridemia was defined as TG ≥150 mg/dl, TG <100 mg/dl as low normal, and TG 100-149 mg/dl as high normal. Normal or high serum LDL-C was defined as a threshold of 116 mg/dl for those at low CV risk and 100 mg/dl for those at moderate CV risk. Plaques were defined as focal protrusions into the arterial lumen of >0.5 mm or >50% of the intima-media thickness (IMT) or a diffuse IMT of >1.5 mm.
Results:
Mean age was 45.5 years and 39% were women; 85% were low risk and 15% moderate risk for CV death. Mean SCORE 10-year risk of CV death was 0.34%. Mean LDL-C was 133 ± 29 mg/dl; mean TG was 92.2 ± 52.3 mg/dl, 11% had TG ≥150 mg/dl, and 68% TG <100 mg/dl. Compared with participants with TG <100 mg/dl, those with TG >150 mg/dl were older, more often men, and had a worse CV risk factor profile and a higher SCORE value. Atherosclerotic plaques were found in 58%, of whom 46.7% of those not on statins had vascular inflammation by PET; 16.8% of subjects had CAC. After multivariate adjustment, TG levels ≥150 mg/dl had a significant association with noncoronary atherosclerosis (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.08-1.80; p = 0.008). There was a 35% higher probability of multiple plaque territories in those with TG ≥150 mg/dl compared to TG <100 mg/dl (p = 0.003). The association was significant for groups with high LDL-C and normal LDL-C. No association was found between TG levels and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR, 2.09; 95% CI, 1.29-3.40; p = 0.003).
Conclusions:
In persons with low to moderate CV risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in those with normal LDL-C levels.
Perspective:
There are ample data in support of the association of TGs with ASCVD and events, but the relationship is not direct. Rather it is associated with TG-rich very LDL (VLDL) remnant particles, which are proinflammatory and proatherogenic, but not as involved with coronary plaque, likely because of size, and less likely to invade the subendothelial space. However, the TGs are also associated with smaller LDL particles, which are more readily entering the subendothelial space and more readily oxidized and taken up by macrophages producing foam cells. The authors did not provide any data on interaction of statins and plaque or inflammatory status, which would be of value.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging
Keywords: Atherosclerosis, Carotid Intima-Media Thickness, Cholesterol, LDL, Diagnostic Imaging, Fluorodeoxyglucose F18, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertriglyceridemia, Inflammation, Plaque, Atherosclerotic, Positron-Emission Tomography, Primary Prevention, Risk Factors, Triglycerides, Ultrasonography, Vascular Diseases
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