Triglycerides Trump HDL-C in Predicting Risk of Cardiovascular Disease

Research based on the Framingham Heart Study Offspring Cohort adds subtlety to conventional notions about the cardiovascular disease (CVD)-protective benefits of high-density lipoprotein cholesterol (HDL-C) (Circ Cardiovasc Qual Outcomes 2016; doi:10.1161/CIRCOUTCOMES.115.002436). The study of 3,590 participants found that HDL-C did not uniformly predict CVD risk, while triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) modified CVD risk at both ends of the HDL-C spectrum.

"There's no question that HDL does have a protective role, as we also confirm in the study, but HDL has been hyped-up," said senior author Michael Miller, MD, in a prepared statement. "HDL really should be viewed as a third priority, with LDL on top and TG second."

Miller and his co-authors conducted the study to further clarify the relationship between HDL-C and CVD risk, in light of HDL-C-raising drugs not demonstrably lowering CVD risk in clinical trials.

Participants had blood samples taken during a baseline visit between 1987 and 1991 and were followed through 2011. The researchers defined the referent group as having isolated low HDL-C <40 mg/dL in men and <50 mg/dL in women, along with both LDL-C and TG <100 mg/dL. They stratified the remaining participants into six groups based on low or high HDL-C and different combinations of TG and LDL-C <100 mg/dL or ≤100 mg/dL.

Compared to participants with isolated low HDL-C, those with low HDL-C and higher levels of TG, HDL-C, or both had 30% to 60% increased risk of CVD. When accompanied by TG and LDL-C ≥100 mg/dL, high HDL-C was not associated with reduced CVD risk. Moreover, the investigators found that TG was associated with CVD risk across HDL-C and LDL-C levels, and they concluded that “TG levels essentially reclassify risk of CVD irrespective of HDL-C.”

GFAP Detects Mild Traumatic Brain Injury for Up to 7 Days After Injury

In the 7 days after injury, glial fibrillary acidic protein (GFAP) consistently detected mild-to-moderate traumatic brain injury (TBI) and traumatic intracranial lesions on computed tomography (CT) and predicted neurosurgical intervention (JAMA Neurology 2016; doi:10.1001/jamaneurol.2016.0039). The findings suggest that this blood-based biomarker could improve early diagnosis of TBI, according to the authors.

"This could ultimately change the way we diagnose concussions, not only in children, but in anyone who sustains a head injury,” said lead author Linda Papa, MD, MSC, an emergency medicine physician at Orlando Regional Medical Center in Orlando, Florida. “We have so many diagnostic blood tests for different parts of the body, like the heart, liver, and kidneys, but there's never been a reliable blood test to identify trauma in the brain. We think this test could change that.”

Prior research has shown that GFAP, an astroglial biomarker, and ubiquitin C-terminal hydrolase L1 (UCH-L1), a neuronal protein, are significantly elevated in patients with TBI who exhibit intracranial lesions on CT. The authors aimed in their current study to establish temporal profiles for both GFAP and UCH-L1.

The study involved 584 trauma patients assessed for mild or moderate TBI. In addition to CT and clinical examination, the subjects had serial GFAP and UCH-L1 testing for up to 7 days after injury. Both GFAP and UCH-L1 were detectable within 1 hour of injury. GFAP peaked at 20 hours post-injury, declined steadily over 72 hours and was still detectable at 7 days. In contrast, UCH-L1 rose and fell more rapidly than GFAP, peaking at 8 hours and decreasing steadily over 48 hours.

During the course of 1 week, GFAP had an area under the curve (AUC) for detecting TBI ranging from 0.73 to 0.94, whereas the AUC for UCH-L1 was 0.30 to 0.67.

Elevated GlycA Appears to Offset Protective Benefit of HDL-C

Elevated levels of glycoprotein acetylation (GlycA), a marker of inflammation, appear to offset the cardioprotective benefit of high-density lipoprotein-cholesterol (HDL-C), according to research presented at the American College of Cardiology Scientific Sessions. Researchers at Intermountain Medical Center in Salt Lake City, Utah wanted to explore whether increased inflammation alters associations of HDL subclasses with coronary artery disease.

The investigators evaluated the association of HDL-particle (HDL-P) subclasses and GlycA and interactions of HDL-P subclasses and GlycA, with cardiac death. The study involved patients who underwent angiography and had both lipoprotein and GlycA measured by nuclear magnetic resonance (NMR) spectroscopy.

The researchers found that elevated levels of GlycA and small and medium HDL-P were independent predictors of cardiac death. Whereas GlycA and small and medium HDL-P were all significantly associated with cardiac death, this was not the case with large HDL-P. Only small HDL-P had a significant interaction with GlycA.

“Our research suggests there’s an interaction between GlycA and small HDL particles that reduces the anti-inflammatory capabilities of HDL and increases a person’s chances of having a heart attack or stroke,” said senior author Brent Muhlestein, MD, co-director of cardiovascular research at the Intermountain Medical Center Heart Institute. “GlycA is a new particle we didn’t know much about, but now that we know there are epidemiologic associations, we need to look at additional ways to evaluate and understand the way it functions and interacts in the bloodstream.”

USPSTF: Screen Individuals at Increased Risk for Syphilis

The U.S. Preventive Services Task Force (USPSTF) in updated guidance recommends screening for syphilis in all non-pregnant individuals at increased risk for the disease, including men who have sex with men, HIV-positive individuals, those who have been incarcerated or who have a history of commercial sex work, and men younger than age 29 (JAMA 2016;315:2321–7). USPSTF concluded with “high certainty” that the net benefit of screening for syphilis in these individuals is “substantial.”

Certain racial and ethnic groups also are at increased risk and would benefit from screening, according to USPSTF. These include African-Americans, Hispanics, and Native Americans.

In making this recommendation—an update from its 2004 statement—USPSTF noted that cases of both primary and secondary syphilis have been on the rise, and the consequences of not treating or delaying treatment for the infection can be high. In addition, syphilis increases the risk of HIV infection.

Typically, screening for syphilis is a two-step process, USPSTF noted, based on antibody detection with an initial nontreponemal test—Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) test—followed by a confirmatory treponemal antibody detection test—fluorescent treponemal antibody absorption [FTA-ABS] or Treponema pallidum particle agglutination [TP-PA] test.

Estimated sensitivities of RPR and VDRL for detecting primary syphilis infection are 86% and 78%, respectively; 100% for detecting secondary syphilis infection; and 98% and 96% for detecting latent syphilis infection, respectively. According to USPSTF, TP-PA and FTA-ABS tests have a sensitivity of 88% and 84%, respectively, for detecting primary syphilis infection and nearly 100% for detecting other stages, and a specificity of 96% to 97%, respectively.

Automated treponemal tests, including enzyme-linked, chemiluminescence, and multiplex flow immunoassays, have been developed and included in a reverse sequence screening algorithm, with these tests performed first, followed by a nontreponemal test. If there is discordance between these results, a second treponemal test (preferably using a different treponemal antibody) is performed. Reported sensitivity ranges from 64% to 100% depending on stage of disease and type of test used, and specificity ranges from 95.4% to 99.9%.

USPSTF reviewed two studies that compared a reverse sequence screening algorithm with the traditional two-step approach to screening, and while both found the reverse sequence screening algorithm detected more cases, they also showed the algorithm had a higher false-positive rate. Based on these findings, USPSTF determined that more research is needed to better understand the use of the reverse sequence algorithm for screening in a primary care setting. USPSTF also noted emerging screening technologies like rapid syphilis tests, but stated that more evidence is needed on the effectiveness of these tests as part of a screening program in a primary care setting.