To summarize recent findings regarding the characterization of lipoprotein disturbances in nonalcoholic fatty liver disease (NAFLD) and their relationship with cardiovascular disease (CVD) and make ...recommendations for the management of this situation.
Advanced lipoprotein profile (using NMR spectroscopy) has shown profound lipoprotein derangements which are overlooked with conventional analyses: increased number and size of very low-density lipoproteins particles, increased number of low-density lipoprotein particles (especially small sized), smaller high-density lipoprotein particles, and an increase in the triglyceride content of all these lipoproteins. Other changes such as impaired functionality of high-density lipoprotein particles have also been observed. Beyond low-density lipoprotein-related parameters, the importance of triglyceride-rich lipoproteins in the pathogenesis of atherosclerosis has recently gained interest. Several studies suggest that these lipoproteins may have an independent role in CVD in NAFLD populations. Although outcome studies with lipid-lowering drugs in NAFLD are lacking, treatment with both statins, and especially, triglyceride-lowering drugs could be promising for these populations at high residual cardiovascular risk.
In addition to being the main determinant of dyslipidemia, disturbances in triglyceride-rich lipoproteins are thought to be the key factor of increased CVD risk in NAFLD. Treatments specifically aimed at modifying these derangements warrant further study in this high-risk population.
Genetic, observational, and clinical intervention studies indicate that circulating levels of triglycerides and cholesterol transported in triglyceride-rich lipoproteins (remnant cholesterol) can ...predict cardiovascular events.
This study evaluated the association of triglycerides and remnant cholesterol (remnant-C) with major cardiovascular events in a cohort of older individuals at high cardiovascular risk.
This study determined the baseline lipid profile and searched for major adverse cardiovascular events (MACEs) in the high-risk primary prevention PREDIMED (Prevención con Dieta Mediterránea) trial population (mean age: 67 years; body mass index: 30 kg/m2; 43% men; 48% with diabetes) after a median follow-up of 4.8 years. Unadjusted and adjusted Cox proportional hazard models were used to assess the association between lipid concentrations (either as continuous or categorical variables) and incident MACEs (N = 6,901; n cases = 263).
In multivariable-adjusted analyses, triglycerides (hazard ratio HR: 1.04; 95% confidence interval CI: 1.02 to 1.06, per 10 mg/dl 0.11 mmol/l; p < 0.001), non−high-density lipoprotein cholesterol (HDL-C) (HR: 1.05; 95% CI: 1.01 to 1.10, per 10 mg/dl 0.26 mmol/l; p = 0.026), and remnant-C (HR: 1.21; 95% CI: 1.10 to 1.33, per 10 mg/dl 0.26 mmol/l; p < 0.001), but not low-density lipoprotein cholesterol (LDL-C) or HDL-C, were associated with MACEs. Atherogenic dyslipidemia (triglycerides >150 mg/dl 1.69 mmol/l and HDL-C <40 mg/dl 1.03 mmol/l in men or <50 mg/dl 1.29 mmol/l in women) was also associated with MACEs (HR: 1.44; 95% CI: 1.04 to 2.00; p = 0.030). Remnant-C ≥30 mg/dl (0.78 mmol/l) differentiated subjects at a higher risk of MACEs compared with those at lower concentrations, regardless of whether LDL-C levels were on target at ≤100 mg/dl (2.59 mmol/l).
In overweight or obese subjects at high cardiovascular risk, levels of triglycerides and remnant-C, but not LDL-C, were associated with cardiovascular outcomes independent of other risk factors.
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Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2D) but also to diabetic vascular complications. It follows that antioxidants might contribute to limiting the diabetes ...burden. In this review we focus on ellagic acid (EA), a compound that can be obtained upon intestinal hydrolysis of dietary ellagitannins, a family of polyphenols naturally found in several fruits and seeds. There is increasing research on cardiometabolic effects of ellagitannins, EA, and urolithins (EA metabolites). We updated research conducted on these compounds and (I) glucose metabolism; (II) inflammation, oxidation, and glycation; and (III) diabetic complications. We included studies testing EA in isolation, extracts or preparations enriched in EA, or EA-rich foods (mostly pomegranate juice). Animal research on the topic, entirely conducted in murine models, mostly reported glucose-lowering, antioxidant, anti-inflammatory, and anti-glycation effects, along with prevention of micro- and macrovascular diabetic complications. Clinical research is incipient and mostly involved non-randomized and low-powered studies, which confirmed the antioxidant and anti-inflammatory properties of EA-rich foods, but without conclusive results on glucose control. Overall, EA-related compounds might be potential agents to limit the diabetes burden, but well-designed human randomized controlled trials are needed to fill the existing gap between experimental and clinical research.
To evaluate the concordance between the 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD (ESC/EASD-2019) and the Steno T1 Risk ...Engine (Steno-Risk) cardiovascular risk scales for individuals with type 1 diabetes (T1D) without cardiovascular disease (CVD) and to analyze the relationships of their use with identification of preclinical atherosclerosis.
We consecutively selected patients with T1D, without CVD, age ≥40 years, with nephropathy, and/or with ≥10 years of T1D evolution with another risk factor. The presence of plaque at different carotid segments was determined by ultrasonography. Cardiovascular risk was estimated in accord with ESC/EASD-2019 risk groups (moderate/high/very high) and the Steno-Risk (<10%, low; 10-20%, moderate; ≥20%, high), as T1D-specific scores. In an exploratory analysis, we also evaluated the non-T1D-specific 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk (ACC/AHA-2013) pooled cohort equation for individuals between 40 and 79 years of age.
We included 501 patients (53% men, mean age 48.8 years, median T1D duration 26.5 years, 41.3% harboring plaques). Concordance between T1D-specific scales was poor (κ = 0.19). A stepped increase in the presence of plaques according to Steno-Risk category was seen (18.4%, 38.2%, and 64.1%, for low, moderate, and high risk, respectively; P for trend <0.001), with no differences according to ESC/EASD-2019 (P = 0.130). Steno-Risk identified individuals with plaques, unlike ESC/EASD-2019 (area under the curve AUC 0.691, P < 0.001, vs. AUC 0.538, P = 0.149). Finally, in polynomial regression models (with adjustment for lipid parameters and cardioprotective treatment), irrespective of the ESC/EASD-2019 category, high risk by Steno-Risk was directly associated with atherosclerosis (in moderate/high-risk by ESC/EASD-2019 odds ratio 2.91 95% CI 1.27-6.72 and 4.94 2.35-10.40 for the presence of plaque and two or more plaques). Similar results were obtained with discordant higher Steno-Risk versus ACC/AHA-2013 (P < 0.001).
Among T1D patients undergoing primary prevention, use of Steno-Risk seems to result in better recognition of individuals with atherosclerosis in comparison with ESC/EASD-2019. Notwithstanding, carotid ultrasound could improve the categorization of cardiovascular risk.
Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the ...therapeutic range and intrapatient variability in predicting rejection and
donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%,
= 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%,
= 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%,
= 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk.
Bilirubin is a potent antioxidant that has been inversely related to cardiovascular disease. There is little information on serum total bilirubin (TB) in relation to atherosclerosis in familial ...dyslipidemia. We assessed the association between TB and carotid and femoral atherosclerosis in this high-risk group.
We evaluated 464 individuals with familial dyslipidemia (56% men; median age, 48 years), 322 with familial hypercholesterolemia, and 142 with familial combined hyperlipidemia. Carotid and femoral arteries were imaged bilaterally with a standardized ultrasonographic protocol. Mean and maximum intima-media thickness and plaque presence (≥1.2 mm) and height were recorded. Cross-sectional associations between TB and atherosclerosis variables were investigated in multivariable-adjusted models, including lipid values and hypolipidemic drug use. Inflammatory markers (C-reactive protein, total leukocyte count, and lipoproteina) were also determined. Increasing TB levels were associated with decreasing intima-media thickness of all carotid segments (
<0.05, all). TB also related to carotid plaque, present in 78% of individuals, and to plaque burden (≥3 plaques), with odds ratios (95% confidence interval) 0.59 (0.36-0.98) and 0.57 (0.34-0.96) for each increase of 0.5 mg in TB, respectively. Findings were confirmed in a validation cohort of 177 subjects with nonfamilial dyslipidemia. Only the familial combined hyperlipidemia group, with higher inflammation-related markers, showed an inverse association between TB and femoral plaque height (β=-0.183;
=0.030).
TB was inversely and independently associated with carotid plaque burden in familial and nonfamilial dyslipidemia. These findings support the use of TB as a biomarker of atherosclerosis in this high-risk group.
The excess risk of fatal and non-fatal cardiovascular events is roughly twice as high in women than in men with type 1 diabetes (T1D).
To evaluate the impact of preeclampsia and parity on sex-based ...discrepancies in preclinical atherosclerosis and on the diagnostic performance of a cardiovascular risk scale.
Cross-sectional study.
Single tertiary hospital.
728 T1D (48.5% women) without cardiovascular disease and age ≥40 years, nephropathy, and/or ≥10 years of diabetes duration with another risk factor.
Standardized carotid ultrasonography.
Carotid plaque determined by ultrasonography and cardiovascular risk estimated according to the Steno T1 Risk Engine (Steno-Risk).
Nulliparous women and parous women without previous preeclampsia had a lower risk for carotid plaque than men (adjusted odds ratio OR: 0.48, 95% confidence interval 0.28-0.82; adjusted OR: 0.51 0.33-0.79, respectively), without differences in the preeclampsia group. The prevalence of carotid plaque increased as the estimated cardiovascular risk increased in all subgroups except for preeclampsia group. The area under the curve (AUC) of the Steno-Risk for identifying ≥2 carotid plaques was lower in the preeclampsia group (men: 0.7886, nulliparous women: 0.9026, women without preeclampsia: 0.8230, preeclampsia group: 0.7841; p between groups=0.042). Neither the addition of parity nor preeclampsia in the Steno-Risk led to a statistically significant increase in the AUC.
The risk for carotid plaque in women compared to men decreased as exposure to obstetric factors diminished. However, the addition of these factors did not improve the prediction of the Steno-Risk.
Evaluate the association between cumulative tobacco consumption (CTC; packs-year) and atherosclerosis in type 1 diabetes (T1D), and study whether the inclusion of CTC in the Steno T1 Risk Engine ...(ST1RE) equation improves the identification of plaques.
Cross-sectional study in T1D patients without cardiovascular disease (CVD), with ≥ 1 of the following: ≥40 years-old, diabetic kidney disease, and/or T1D duration ≥ 10 years + cardiovascular risk factors.Preclinical atherosclerosis was evaluated by carotid ultrasonography.
N = 584 patients were included (46.1 % women, age 48.7 ± 10.5 years, T1D duration 27.3 ± 10.8 years, 26.2 % active smokers). The overall plaque prevalence was 40.9 %. In models adjusted for age, sex, lipids, blood pressure, kidney function, statin use, microvascular complications and HbA1c, CTC was dose-dependently associated with the number of plaques (none, 1–2, ≥3) overall and in both active and former smokers (p < 0.001). This association remained after adjusting for ST1RE (OR 1.11 1.02–1.19). Although the inclusion of CTC in the ST1RE did not improve plaque identification overall (p = 0.180), it did so when analyzing active smokers separately (AUC 0.738 vs. 0.768; p < 0.01).
In T1D patients, CTC is dose-dependently associated with atherosclerosis. Further prospective studies are needed to determine if CTC could identify T1D individuals more prone to accelerated atherosclerosis.
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