Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion-ordered ¹H NMR spectroscopy. Our method uses diffusion coefficients to provide a direct measure of the mean particle sizes and numbers. Using 177 plasma samples from healthy individuals and the concentration of apolipoprotein B and A from isolated lipoprotein fractions our test showed a stronger correlation between the NMR-derived lipoprotein particle numbers and apolipoprotein concentrations than the LipoProfile^® test commercialized by Liposcience. We also converted LDL particle numbers to ApoB equivalents (mg/dL) and our test yielded similar values of LDL-ApoB than the LipoProfile^® test (absolute mean bias of 8.5 and 7.4 mg/dL, respectively). In addition, our HDL-P values were more concordant with the calibrated values determined recently using ion mobility. Finally, principal component analysis distinguished type 2 diabetic patients with and without atherogenic dyslipidemia (AD) on a second cohort of 307 subjects characterized using the Liposcale test (AUC=0.88) and showed concordant relationships between variables explaining AD. Altogether, our method provides reproducible and reliable characterization of lipoprotein particles and it is applicable to pathological states such as AD.

Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90–95% of cases are type 2 diabetes mellitus. This is partly attributed to the surge in the prevalence of obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as the primary cause of morbidity and mortality, placing a substantial burden on healthcare systems due to the potential for macrovascular and microvascular complications. In this context, leptin, an adipocyte-derived hormone, plays a fundamental role. This hormone is essential for regulating the cellular metabolism and energy balance, controlling inflammatory responses, and maintaining CV system homeostasis. Thus, leptin resistance not only contributes to weight gain but may also lead to increased cardiac inflammation, greater fibrosis, hypertension, and impairment of the cardiac metabolism. Understanding the relationship between leptin resistance and CV risk in obese individuals with type 2 DM (T2DM) could improve the management and prevention of this complication. Therefore, in this narrative review, we will discuss the evidence linking leptin with the presence, severity, and/or prognosis of obesity and T2DM regarding CV disease, aiming to shed light on the potential implications for better management and preventive strategies.

—Mice expressing human apolipoprotein A-IV (apoA-IV) mainly in the intestine were obtained in an apolipoprotein E–deficient (apoE ₀ ) background (apoA-IV/E ₀ mice). Quantification of aortic lesions and plasma lipid determination showed that compared with their control apoE ₀ counterparts, the apoA-IV/E ₀ mice are protected against atherosclerosis without an increase in HDL cholesterol. Because oxidized lipoproteins play an important role in atherogenesis, we tested whether the protection observed in these animals is accompanied by an in vivo reduction of the oxidation parameters. The lag time in the formation of conjugated dienes during copper-mediated oxidation, the aggregation state of LDL, and the presence of anti–oxidized LDL antibodies were measured. The presence of oxidized proteins in tissues and the presence of oxidation-specific epitopes in heart sections of atherosclerotic lesions were also analyzed. Except for lag time, the results showed that the oxidation parameters were reduced in the apoA-IV/E ₀ mice compared with the apoE ₀ mice. This suggests that human apoA-IV acts in vivo as an antioxidant. In addition, human apoA-IV accumulation was detected in the atherosclerotic lesions of apoA-IV/E ₀ mice, suggesting that apoA-IV may inhibit oxidative damage to local tissues, thus decreasing the progression of atherosclerosis.

Familial combined hyperlipidemia (FCHL) is the commonest form of hereditary hyperlipidemia (1) (2). Its primary defect is increased secretion of hepatic triglyceride (TG)-rich apolipoprotein B (apo B)-containing particles (VLDL) (3) and impaired clearance of postprandial lipoproteins (4), which increases the number of circulating TG-rich lipoproteins. FCHL is present in up to 20% of survivors of myocardial infarction, and it is considered a significant genetic risk factor for developing cardiovascular disease (1) (5). The underlying genetic defect is unknown, although the disease has been linked to chromosomes 1 (6) and 11 (7). With regard to the latter, linkage has been identified in the AI-CIII-AIV cluster, encoded in chromosome 11q23-q24, which has been repeatedly associated with FCHL as a site involved in modulating expression of the disease (8) (9). This is in part explained by the role of apo C-III as a negative regulator of TG hydrolysis. Despite considerable effort, no functional variant has been detected that explains such modulatory action, and the search has been extended to the surrounding regions. In this context, the newly identified apo AV gene (APOAV) (10) (11), adjacent to the AI-CIII-AIV gene cluster and with a clear impact on TG metabolism in animals (10), becomes a candidate. Association of this gene with plasma TG concentrations has also been reported in humans (10). We have explored such an association in FCHL.

The widespread use of protease inhibitors (PI) has been associated with abnormalities in the lipid profile of HIV-1-infected patients. Treatment simplification approaches in which PI are replaced by nevirapine (NVP) have been shown to improve PI-related toxicity. To assess the impact on plasma lipids of replacing the PI by NVP in HIV-1 infected patients with lipodystrophy. We studied 34 patients with lipodystrophy who had been the first to be enrolled in a prospective, randomized trial of continuing current treatment, or replacing PI with NVP. Sixteen patients replaced their PI with NVP and 18 continued their current PI-containing treatment. Total, low density lipoprotein (LDL), very low density lipoprotein (VLDL), intermediate density lipoprotein and high density lipoprotein (HDL) cholesterol and triglyceride levels, the size and particle number of LDL were determined at baseline and after 24 weeks, by nucleic magnetic resonance spectroscopy. After 24 weeks of replacing the PI with NVP, we observed a reduction of total cholesterol (P = 0.028), LDL-cholesterol (P = 0.001), the number of circulating LDL particles (P = 0.003) and the VLDL-1 triglyceride level (P = 0.032). A concomitant significant increase was observed in both HDL-cholesterol level (P = 0.002) and HDL particle size (P < 0.001). No significant changes were observed in the group that continued taking the PI. The replacement of PI by NVP improved the lipid profile both by reducing the number and lipid content of atherogenic LDL particles, and increasing the protective HDL fraction. Although total triglyceride levels remained unchanged, a reduction in the VLDL-1 fraction contributes to the reduction of LDL particles. These changes are expected to reduce the risk of cardiovascular disease in HIV-1-infected patients on highly active antiretroviral therapy.