Antonio J. Amor

Prevalence by sex of preclinical carotid atherosclerosis in newly diagnosed type 2 diabetes

BACKGROUND AND AIMS There is clinical trial evidence that only early, intensive risk factor control can reduce cardiovascular disease (CVD) morbidity and mortality in type 2 diabetes (T2DM). However, there is little information regarding preclinical atherosclerosis at diabetes diagnosis. We assessed carotid atherosclerosis in new-onset T2DM and control individuals without prior CVD. METHODS AND RESULTS In a cross-sectional case-control study, we determined intima-media thickness (IMT) and plaque (IMT ≥1.5 mm) by ultrasound at all carotid sites in new-onset T2DM patients and controls. We assessed 106 T2DM patients, median age 62 years, 46% women, 19% smokers, 54% with hypertension, and 41% with dyslipidemia and 99 non-diabetic subjects matched by age, sex, and cardiovascular risk factors. Compared to controls, T2DM patients had higher common carotid artery (CCA)-IMT (median 0.725 vs. 0.801 mm, p = 0.01), bulb-IMT (0.976 vs. 1.028 mm, p = 0.12), and internal carotid artery (ICA)-IMT (0.727 vs. 0.802 mm, p = 0.04). The prevalence of total plaque (60% vs. 72%, p = 0.06), ICA plaque (20% vs. 42%, p < 0.01), and harboring ≥3 plaques (16% vs. 35% p < 0.01) was also higher in T2DM. Plaque score (sum of maximum plaque heights) was also higher (p < 0.01) in T2DM. Diabetic women showed more advanced carotid atherosclerosis than diabetic men when they were compared with their respective non-diabetic counterparts. CONCLUSIONS There is a high prevalence of preclinical atherosclerosis (carotid plaque presence and burden) in new-onset T2DM subjects, especially in women. Early, still reversible, preclinical atherosclerosis may explain in part why early intervention is effective to prevent CVD in this patient population.

Nuclear magnetic resonance lipoprotein abnormalities in newly-diagnosed type 2 diabetes and their association with preclinical carotid atherosclerosis

BACKGROUND AND AIMS Atherogenic dyslipidemia is common in type 2 diabetes (T2DM) and predicts cardiovascular disease, but information on the association of its components with atherosclerosis is scarce. We aimed to assess differences in the lipoprotein profile in newly-diagnosed T2DM and matched control individuals and their associations with preclinical carotid atherosclerosis. METHODS In a case-control study, we evaluated lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy and determined carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) by B-mode ultrasonography. RESULTS We assessed 96 T2DM patients (median age 63 years, 44% women, 19% smokers, 54% hypertension, 38% dyslipidemia) and 90 non-diabetic controls matched for age, sex, and cardiovascular risk factors. In T2DM VLDL-particles (mainly large and enriched in cholesterol and triglycerides) were increased, and large HDL-particles (enriched in triglycerides and depleted in cholesterol) were reduced (p < 0.05; all comparisons). Regarding associations with preclinical atherosclerosis, VLDL triglyceride content (odds ratio [OR], 8.975; 95% confidence interval [CI], 2.330-34.576), total number of VLDL particles (OR, 2.713; CI, 1.601-4.598) and VLDL size (OR, 2.044; CI, 1.320-3.166), and the ratio cholesterol/triglycerides in HDL (OR, 0.638; CI, 0.477-0.852) were associated with plaque burden (≥3 plaques) independently of confounders, including conventional lipid levels. CONCLUSION NMR-assessed advanced lipoprotein profile identifies lipid abnormalities associated with newly-diagnosed T2DM and preclinical atherosclerosis that are not captured by the traditional lipid profile. At this early stage of diabetes, NMR lipoproteins could be useful to identify candidates for a more comprehensive cardiovascular risk prevention strategy.

Estimating Cardiovascular Risk in Spain by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice

INTRODUCTION AND OBJECTIVES There are no nationwide, population-based studies in Spain assessing overall cardiovascular risk. We aimed to describe cardiovascular risk and achievement of treatment goals following the 2012 European Guidelines on cardiovascular disease prevention strategy. We also investigated clinical characteristics (non-classical risk factors) associated with moderate risk. METHODS Participants (n=2310, 58% women) aged 40 to 65 years from a national population-based study (Di@bet.es Study) were identified. First, a priori high/very-high risk individuals were identified. Next, total cardiovascular risk (Systematic Coronary Risk Evaluation equation including high-density lipoprotein cholesterol) was used to assess risk of a priori non-high risk individuals. Variables independently associated with moderate versus low-risk were investigated by multiple logistic regression analysis. RESULTS Age-and-sex standardized (direct method) percentages of high/very-high, moderate, and low-risk were 22.8%, 43.5%, and 33.7%, respectively. Most men were at moderate (56.2%), while 55.4% of women were at low risk. Low-density lipoprotein cholesterol (< 70,<100, < 115 mg/dL) and blood pressure (<140/90 mmHg) goals for very-high, high and moderate risk were met in 15%, 26% and 46%, and 77%, 68% and 85% of the individuals, respectively. Body mass index, high triglycerides concentrations, diastolic blood pressure, and low Mediterranean diet adherence (in women) were independently associated with moderate (versus low) risk. CONCLUSIONS Cardiovascular risk in Spain is mainly moderate in men and low in women. Achievement of treatment goals in high-risk individuals should be improved. The prevalence of non-classical cardiovascular risk factors is elevated in subjects at moderate risk, an important aspect to consider in a population-based strategy to decrease cardiovascular disease in the most prevalent group.

Enfermedad cardiovascular en pacientes con diabetes mellitus tipo 1 y tipo 2 en España

BACKGROUND AND OBJECTIVE To describe the prevalence of cardiovascular disease (CVD) in type 1 diabetes (T1DM) and to compare it with that observed in type 2 diabetes (T2DM) and normal population in Spain. PATIENTS AND METHODS Cross-sectional study (18-70 years-old). Information on CVD was available from a nurse-administered questionnaire (Di@bet.es Study, NORMAL=3,430, T2DM=312) and from a physician reporting form (T1DM=1,382). Differences in the crude and adjusted prevalence of coronary heart (CHD), cerebrovascular (CNSD), peripheral vascular (PVD) and overall CV (CVD) disease were investigated between T1DM vs. NORMAL, and T1DM vs. T2DM groups. RESULTS We found differences in age, body mass index, proportion of women, dyslipemia and antihypertensive medication between T1DM vs. NORMAL and T1DM vs. T2DM (all P<.001). Smoking prevalence was not different between T1DM vs. T2DM and it was lower in T1DM compared to NORMAL (P<.0001). The percentage of CHD, CNSD, PVD, and overall CVD in T1DM vs. NORMAL was 3.0 vs. 2.5 (P=.31), 0.70 vs. 1.10 (P=.22), 2.61 vs. 0.20 (P<.0001), and 5.1 vs. 3.44 (P<.01), respectively. The prevalence in T2DM (vs. T1DM) was 11.3 (P<.0001), 3.5 (P<.0001), 4.2 (P=.13), and 17% (P<.0001), respectively. Multiple logistic regression adjusted models showed a higher prevalence of CHD (odds ratio [OR] 2.27, 95% confidence interval [95% CI] 1.41-3.67), PVD (OR 15.35, 95% CI 5.61-42.04), and overall CVD (OR 2.32, 95% CI 1.55-3.46), but not for CNSD (OR 0.49, 95% CI 0.19-1.27) in T1DM compared to NORMAL. No differences were found between T1DM and T2DM. CONCLUSIONS We found a higher prevalence of CVD in a Mediterranean population of T1DM individuals compared with non-diabetic subjects. This prevalence was similar to that observed in T2DM.

Prediction of Cardiovascular Disease by the Framingham‐REGICOR Equation in the High‐Risk PREDIMED Cohort: Impact of the Mediterranean Diet Across Different Risk Strata

Background The usefulness of cardiovascular disease (CVD) predictive equations in different populations is debatable. We assessed the efficacy of the Framingham‐REGICOR scale, validated for the Spanish population, to identify future CVD in participants, who were predefined as being at high‐risk in the PREvención con DIeta MEDiterránea (PREDIMED) study—a nutrition‐intervention primary prevention trial—and the impact of adherence to the Mediterranean diet on CVD across risk categories. Methods and Results In a post hoc analysis, we assessed the CVD predictive value of baseline estimated risk in 5966 PREDIMED participants (aged 55–74 years, 57% women; 48% with type 2 diabetes mellitus). Major CVD events, the primary PREDIMED end point, were an aggregate of myocardial infarction, stroke, and cardiovascular death. Multivariate‐adjusted Cox regression was used to calculate hazard ratios for major CVD events and effect modification from the Mediterranean diet intervention across risk strata (low, moderate, high, very high). The Framingham‐REGICOR classification of PREDIMED participants was 25.1% low risk, 44.5% moderate risk, and 30.4% high or very high risk. During 6‐year follow‐up, 188 major CVD events occurred. Hazard ratios for major CVD events increased in parallel with estimated risk (2.68, 4.24, and 6.60 for moderate, high, and very high risk), particularly in men (7.60, 13.16, and 15.85, respectively, versus 2.16, 2.28, and 3.51, respectively, in women). Yet among those with low or moderate risk, 32.2% and 74.3% of major CVD events occurred in men and women, respectively. Mediterranean diet adherence was associated with CVD risk reduction regardless of risk strata (P>0.4 for interaction). Conclusions Incident CVD increased in parallel with estimated risk in the PREDIMED cohort, but most events occurred in non–high‐risk categories, particularly in women. Until predictive tools are improved, promotion of the Mediterranean diet might be useful to reduce CVD independent of baseline risk. Clinical Trial Registration URL: http://www.Controlled-trials.com. Unique identifier: ISRCTN35739639.

Dietary polyunsaturated fatty acids mediate the inverse association of stearoyl-CoA desaturase activity with the risk of fatty liver in dyslipidaemic individuals

PurposeThe activity of stearoyl-CoA desaturase-1 (SCD1) is increased in non-alcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) inhibit SCD1, but clinical studies on whether all dietary PUFA species are equal in SCD1 inhibition are scarce. Serum phospholipids are an objective proxy of dietary intake of plant-derived PUFA (C18:2n-6, C18:3n-3) and marine-derived PUFA (C20:5n-3, C22:6n-3). In 355 participants with primary dyslipidemia, we cross-sectionally investigated whether the presumed association between surrogate markers of NAFLD and SCD1 activity is mediated by intake of PUFA, and, if it is, what PUFA species are relevant in this regard.MethodsWe determined the fatty acid profile of serum phospholipids by gas chromatography, and used the ratio C16:1n-7/C16:0 as a marker of SCD1 activity. NAFLD was diagnosed by values ≥ 60 in the fatty liver index (FLI), a surrogate recently validated against ultrasonography.ResultsFLI ≥ 60 was detected in 37.5% (n = 133) of study participants. In a multivariate model, SCD1 activity showed an expected significant association with the risk of NAFLD, with odds ratio (OR) (95% confidence interval) of 1.44 (1.04–2.01) for each 0.01 increase. In a model further allowing the stepwise inclusion of plant-derived PUFA, marine-derived PUFA, and total PUFA (vegetable + marine), total PUFA replaced SCD1 activity as a significant (inverse) association of NAFLD, with OR 0.89 (0.81–0.99).ConclusionsTotal PUFA, regardless of their origin, mediates the relationship between SCD1 activity and NAFLD. This provides a new insight in the protective effects of PUFA against NAFLD, heretofore mostly focussed on PUFA species from marine origin.

Relationship Between Total Serum Bilirubin Levels and Carotid and Femoral Atherosclerosis in Familial DyslipidemiaHighlights

Objective— 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. Approach and Results— 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 lipoprotein[a]) were also determined. Increasing TB levels were associated with decreasing intima-media thickness of all carotid segments (P<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 (&bgr;=−0.183; P=0.030). Conclusions— 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.

Erratum. Mediterranean Diet, Retinopathy, Nephropathy, and Microvascular Diabetes Complications: A Post Hoc Analysis of a Randomized Trial. Diabetes Care 2015;38:2134–2141

Some imperfections in the randomization procedures affecting a small subset of participants in the Prevencion con Dieta Mediterranea (PREDIMED) trial (at most 14%) have been reported in a recent republication of the main PREDIMED article (see Estruch et al. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34). For this reason, the authors wish to make the …

Detailed description of a prepregnancy care program and its impact on maternal glucose control, weight gain, and dropouts.

The aim of this study was to analyze the clinical and metabolic changes observed during a prepregnancy care (PPC) program.

The proportion of total C18:1 trans-fatty acids in red blood cell membranes relates to carotid plaque prevalence

Consistent evidence supports the pro-atherogenic properties of dietary trans-fatty acids (TFAs). However, there are no clinical data on TFA intake and atheroma plaque. We cross sectionally investigated whether the proportion of total C18:1 TFA in red blood cells (RBCs), which mirrors dietary TFA intake, independently relates to carotid plaque prevalence in subjects with new-onset type 2 diabetes mellitus without prior cardiovascular disease (n=101, 56% men, mean age 61 years) and age- and sex-matched controls (n=96). RBC fatty acid composition was determined by gas chromatography. Plaque (defined as carotid intima-media thickness ≥1.5 mm) was sonographically assessed at three bilateral carotid segments. In multivariate models adjusting for group (diabetes or control) and classical cardiovascular risk factors, for each 0.1% increase in RBC total C18:1 TFA isomers, plaque prevalence increased by 53% (P=.002). In contrast, for each 0.1% increase in RBC alpha-linolenic acid, the vegetable omega-3 fatty acid, plaque prevalence decreased by 43% (P<.001). We conclude that the RBC membrane proportion of total C18:1 TFA, considered a proxy of intake, directly relates to the ultrasound feature that best predicts future cardiovascular events. Our findings support current recommendations to limit TFA intake for cardiovascular health promotion.