Biomarker Commons

Triglycerides: how much credit do they deserve?

Med Clin North Am. 2012 Jan;96(1):39-55

Authors: Kohli P, Cannon CP

Abstract
In the modern era of statin therapy, major advances have been made in treating coronary heart disease. However, despite intensive treatment with statin therapy, residual cardiovascular risk persists and has been attributed to the persistence of atherogenic dyslipidemia and, in part, elevated triglycerides (TGs). In this review, the authors focus on the mechanism of elevated TGs and provide a discussion of the challenges of measuring TGs as a biomarker, its role in the pathogenesis of atherosclerotic heart disease, and results of several recent studies that have elucidated the relationship between TGs and cardiovascular morbidity and mortality.

PMID: 22391250 [PubMed - indexed for MEDLINE]

Altered serum selenium and uric acid levels and dyslipidemia in hemodialysis patients could be associated with enhanced cardiovascular risk.

Biol Trace Elem Res. 2011 Dec;144(1-3):496-503

Authors: Martí del Moral L, Agil A, Navarro-Alarcón M, López-Ga de la Serrana H, Palomares-Bayo M, Oliveras-López MJ

Abstract
In the present study, the first objective was to follow up serum selenium (Se) concentrations in 117 hemodialysis patients (HPs) during a 2-year longitudinal study, relating concentrations to biochemical indexes (n = 6; namely lipoprotein profile, uric acid, and total protein levels). It was also evaluated whether the disease is associated with an enhanced cardiovascular risk. A healthy control group (n = 50) was also studied. Mean serum Se levels were significantly lower in HPs than in the controls (p = 0.002); mean levels significantly increased from the first to third blood sampling (p < 0.001). HPs showed a marked dyslipidemia, with a significant reduction in total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol levels and a significant increase in triglyceride levels (p < 0.001). HPs showed a marked hyperuricemia (p < 0.001). Serum selenium levels in HPs were correlated negatively with uric acid levels (inflammation biomarker; p < 0.01). In HPs, serum Se levels are reduced due to their disease (chronic renal failure). Serum Se levels rose until the third blood sampling. The marked dyslipidemia and hyperuricemia found in HPs and the negative correlation between the serum Se and uric acid levels in these patients could imply an enhanced cardiovascular risk.

PMID: 21789541 [PubMed - indexed for MEDLINE]

Associations between lipid levels and migraine: cross-sectional analysis in the epidemiology of vascular ageing study.

Cephalalgia. 2011 Oct;31(14):1459-65

Authors: Rist PM, Tzourio C, Kurth T

Abstract
BACKGROUND: Migraine with aura has been associated with increased prevalence of cardiovascular risk factors, including elevated levels of some vascular biomarkers. However, little research has been done on this association among the elderly. We examined the associations of lipid levels with headache and migraine in a cohort of elderly individuals.
METHODS: Cross-sectional study among 1155 participants enrolled in the Epidemiology of Vascular Ageing Study with available information on headache and blood biomarkers. We used multinomial logistic regression to evaluate the association between biomarker tertiles and headache categories.
RESULTS: 925 people had no severe headache, 64 people had non-migraine headache and 166 people had migraine, of whom 23 had aura. Compared with participants without headache, we observed strong associations between increasing tertiles of total cholesterol and migraine with aura. The odds ratio (95% confidence interval) was 4.67 (0.99-21.97) for the 2nd tertile and 5.97 (1.29-27.61) for the 3rd tertile. We also found strong associations between triglycerides and migraine with aura (odds ratio for 3rd tertile: 4.42 (1.32-14.77)). We did not see significant associations between increased biomarker levels and any other headache group.
CONCLUSIONS: Elevated levels of total cholesterol and triglycerides are associated with migraine with aura but not other headache forms in the elderly.

PMID: 21926156 [PubMed - indexed for MEDLINE]

Effects of combination therapy with rosuvastatin and fenofibric acid in patients with mixed dyslipidemia and high-sensitivity C-reactive protein (≥ 2 mg/L). cmb@bcm.tmc.edu.

J Clin Lipidol. 2011 Sep;5(5):401-7

Authors: Ballantyne CM, Davidson MH, Setze CM, Kelly MT

Abstract
BACKGROUND: Elevated levels of high-sensitivity C-reactive protein (hsCRP) correlate with an increased risk for cardiovascular events. Combination therapy with a statin and a fibrate may be more effective than statin monotherapy for reducing hsCRP, especially in patients with mixed dyslipidemia.
OBJECTIVE: To characterize the treatment effects of rosuvastatin and fenofibric acid combination therapy compared with individual monotherapies in mixed dyslipidemic patients with baseline hsCRP ≥2 mg/L versus <2 mg/L and to determine the effects of long-term treatment with rosuvastatin and fenofibric acid combination therapy on hsCRP and other lipids for patients with hsCRP ≥2 mg/L after treatment with rosuvastatin monotherapy.
METHODS: Data for the post hoc analysis were derived from two 12-week controlled studies and a 52-week extension study. Patients were treated with fenofibric acid 135 mg; rosuvastatin 5, 10, 20, or 40 mg; or rosuvastatin 5, 10, or 20 mg and fenofibric acid 135 mg in the controlled studies; and with rosuvastatin 20 mg and fenofibric acid 135 mg in the extension study.
RESULTS: In this analysis, 65% (1416/2182) of patients had pretreatment baseline hsCRP ≥2 mg/L. Among all treatment groups, larger decreases in hsCRP were observed in patients with greater baseline hsCRP; however, improvements in other lipids/apolipoprotein were comparable between the baseline hsCRP categories. Among patients with high hsCRP (≥2 mg/L) remaining after 12 weeks of rosuvastatin 10, 20, or 40 mg monotherapy, hsCRP was reduced by ∼36% after switching to rosuvastatin 20 mg and fenofibric acid 135 mg for up to 52 weeks, and ∼36% of patients shifted from hsCRP ≥2 mg/L to <2 mg/L.
CONCLUSIONS: Combination therapy with rosuvastatin and fenofibric acid may be effective for improving the inflammatory biomarker, hsCRP as well as other lipid abnormalities in patients with mixed dyslipidemia and high hsCRP.

PMID: 21981842 [PubMed - indexed for MEDLINE]

ApoB100/LDLR-/- hypercholesterolaemic mice as a model for mild cognitive impairment and neuronal damage.

PLoS One. 2011;6(7):e22712

Authors: Ramírez C, Sierra S, Tercero I, Vázquez JA, Pineda A, Manrique T, Burgos JS

Abstract
Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD). Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR]) of human familial hypercholesterolaemia (FH). From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100) levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions) concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing) and impairment of the episodic-like memory (determined by the integrated memory test). This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline.

PMID: 21829488 [PubMed - indexed for MEDLINE]