Contribution of APOE Genetic Variants to Dyslipidemia.

BACKGROUND: apo (apolipoprotein) E has crucial role in lipid metabolism. The genetic variation in APOE gene is associated with monogenic disorders and contributes to polygenic hypercholesterolemia and to interindividual variability in cholesterol. APOE rare variants may be involved in the phenotype of genetic hyperlipidemias. METHODS: Exon 4 of APOE were sequenced in all consecutive unrelated subjects with primary hyperlipidemia from a Lipid Unit (n=3667) and 822 random subjects from the Aragon Workers Health Study. Binding affinity of VLDL (very low-density lipoprotein) to LDL receptor of pathogenic predicted apoE variants was analyzed in vitro. Lipoprotein particle number, size, and composition were studied by nuclear magnetic resonance. RESULTS: In addition to common polymorphisms giving rise to APOE2 and APOE4, 14 gene variants were found in exon 4 of APOE in 65 subjects. p.(Leu167del) in 8 patients with isolated hypercholesterolemia and in 8 patients with combined hyperlipidemia. Subjects with p.(Arg121Trp), p.(Gly145Asp), p.(Arg154Ser), p.(Arg163Cys), p.(Arg165Trp), and p.(Arg168His) variants met dysbetalipoproteinemia lipid criteria and were confirmed by nuclear magnetic resonance. VLDL affinity for the LDL receptor of p.(Arg163Cys) and p.(Arg165Trp) heterozygous carriers had intermedium affinity between APOE2/2 and APOE3/3. p.(Gly145Asp) and p.(Pro220Leu) variants had higher affinity than APOE3/3. CONCLUSIONS: APOE genetic variation contributes to the development of combined hyperlipidemia, usually dysbetalipoproteinemia, and familial hypercholesterolemia. The lipid phenotype in heterozygous for dysbetalipoproteinemia-associated mutations is milder than the homozygous APOE2/2-associated phenotype. Subjects with dysbetalipoproteinemia and absence of APOE2/2 are good candidates for the study of pathogenic variants in APOE. However, more investigation is required to elucidate the significance of rarer variants of apoE.

Toxic Metals and Subclinical Atherosclerosis in Carotid, Femoral, and Coronary Vascular Territories: The Aragon Workers Health Study.

OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. Approach and Results: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score ≥1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 µg/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmium-titanium exposure. CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.

The intake of flavonoids, stilbenes, and tyrosols, mainly consumed through red wine and virgin olive oil, is associated with lower carotid and femoral subclinical atherosclerosis and coronary calcium.

PURPOSE: It is suggested that polyphenols back the cardiovascular protection offered by the Mediterranean diet. This study evaluates the association of specific types of dietary polyphenols with prevalent subclinical atherosclerosis in middle-aged subjects. METHODS: Ultrasonography and TC were performed on 2318 men from the Aragon Workers Health Study, recruited between 2011 and 2014, to assess the presence of plaques in carotid and femoral arteries and coronary calcium. Polyphenol intake was assessed using a validated semi-quantitative 136-item food frequency questionnaire. The Phenol Explorer database was used to derive polyphenol class intake. Logistic and linear regressions were used to estimate the cross-sectional association of polyphenols intake with femoral and carotid subclinical atherosclerosis and coronary calcium. RESULTS: A higher intake of flavonoids (third vs. first tertile) was associated with a lower risk of both carotid (OR 0.80: CI 95% 0.62-1.02; P trend 0.094) and femoral (0.62: 0.48-0.80, P trend < 0.001) subclinical atherosclerosis. A higher intake of stilbenes was associated with a lower risk of femoral subclinical atherosclerosis (0.62: 0.46-0.83; P trend 0.009) and positive coronary calcium (0.75: 0.55-1.03; P trend 0.131). A higher intake of tyrosols was also associated with a lower risk of positive coronary calcium (0.80: 0.62-1.03; P trend 0.111). The associations remained similar when adjusted for blood lipids and blood pressure. CONCLUSION: Dietary flavonoids, stilbenes, and tyrosols, whose main sources are red wine and virgin olive oil, are associated with lower prevalence of subclinical atherosclerosis in middle-aged subjects.

Current causes of death in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by high low-density lipoprotein cholesterol (LDLc) and a high risk of premature cardiovascular disease (CVD). The molecular bases have been well defined, and effective lipid lowering is possible. This analysis aimed to study the current major causes of death of genetically defined heterozygous familial hypercholesterolemia (heFH). METHODS: A case‒control study was designed to analyse life-long mortality in a group of heFH and control families. Data from first-degree family members of cases and controls (nonconsanguineous cohabitants), including deceased relatives, were collected from a questionnaire and review of medical records. Mortality was compared among heFH patients, nonheFH patients, and nonconsanguineous family members. RESULTS: A total of 813 family members were analysed, 26.4% of whom were deceased. Among the deceased, the mean age of death was 69.3 years in heFH individuals, 73.5 years in nonheFH individuals, and 73.2 years in nonconsanguineous individuals, without significant differences. CVD was the cause of death in 59.7% of heFH individuals, 37.7% of nonheFH individuals, and 37.4% of nonconsanguineous individuals (P = 0.012). These differences were greater after restricting the analyses to parents. The hazard ratio of dying from CVD was 2.85 times higher (95% CI, (1.73-4.69) in heFH individuals than in individuals in the other two groups (non-FH and nonconsanguineous), who did not differ in their risk. CONCLUSIONS: CVD mortality in heFH individuals is lower and occurs later than that described in the last century but is still higher than that in non-FH individuals. This improved prognosis of CVD risk is not associated with changes in non-CVD mortality.

APOE Genotypes Modulate Inflammation Independently of Their Effect on Lipid Metabolism.

The association between APOE genotypes and cardiovascular disease (CVD) is partially mediated by LDL-cholesterol concentration but persists after adjusting for lipid levels and other cardiovascular risk factors. Data from the Aragon Workers Health Study (AWHS) (n = 4159) and the Lipid Unit at the Hospital Universitario Miguel Servet (HUMS) (n = 3705) were used to investigate the relationship between C-reactive protein (CRP) levels and APOE genotype. Lipoprotein particle and GlycA concentrations were analyzed in a subsample from AWHS. APOE genotyping was carried out by the Sanger method in both cohorts. APOE4 carriers had significantly lower levels of CRP than APOE3 carriers. Furthermore, APOE4 carriers had cholesterol-enriched LDL particles compared to APOE2 carriers. APOE4 carriers also had higher concentrations of small, medium, and large LDL particles. CRP levels were not associated with lipoprotein particle number, size, or composition. GlycA levels were not associated with APOE genotypes. However, GlycA levels were significantly associated with the size and the amount of cholesterol contained in HDL, VLDL, and LDL particles. APOE genotype influences CRP concentration regardless of lipid profile. APOE2 carriers showed the highest CRP levels, followed by APOE3 and APOE4. A more atherogenic lipid profile, but not inflammatory markers could partly explain the higher CVD risk observed in APOE4 carriers.

High consumption of ultra-processed food may double the risk of subclinical coronary atherosclerosis: the Aragon Workers' Health Study (AWHS).

BACKGROUND: Ultra-processed food (UPF) consumption, which is increasing worldwide, has recently been associated with an increased risk of death and cardiovascular disease. We aimed to assess whether consumption of UPF is directly associated with subclinical coronary atherosclerosis in middle-aged men. METHODS: A computed tomography scan was performed on 1876 men from the Aragon Workers' Health Study, recruited from January 2011 to December 2014, to assess coronary calcium. All participants were free of coronary heart disease. Dietary intake was collected by a validated 136-item semi-quantitative food frequency questionnaire. UPF was defined according to the NOVA classification. Associations between consumption of total energy-adjusted UPF and Coronary Calcium Agatston Score (CACS)-categorized into CACS of 0, > 0 and < 100, and ≥ 100-were cross-sectionally assessed by generalized ordered logistic regression adjusted for main confounders. RESULTS: No coronary calcium was detected in 60.2% of the participants, whereas 10.2% had a CACS ≥ 100. A significant dose-response association was observed between energy-adjusted UPF consumption and the risk of having a CACS ≥ 100, when compared with those in the lowest CACS categories (CACS of 0 together with CACS > 0 and < 100). The fully adjusted ORs (95% CI) of having a CACS ≥ 100 across quartiles of energy-adjusted UPF consumption (approximately 100 g/day in the lowest quartile (ref.) and 500 g/day in the highest) were 1.00 (ref.), 1.50 (0.93, 2.42), 1.56 (0.96, 2.52), and 2.00 (1.26, 3.16), p trend .005. CONCLUSION: In this middle-aged worker's sample, approximately 500 g/day of UPF consumption was associated with a 2-fold greater prevalence of subclinical coronary atherosclerosis than consuming only 100 g/day, independently of total energy intake and other well-established cardiovascular risk factors.

Three Dimensional Carotid and Femoral Ultrasound is not Superior to Two Dimensional Ultrasound as a Predictor of Coronary Atherosclerosis Among Men With Intermediate Cardiovascular Risk.

BACKGROUND: Current cardiovascular disease (CVD) risk stratification scales, drawn up from traditional risk factors, have important limitations. The detection of subclinical atherosclerosis, by a non-invasive technique such as peripheral arteries ultrasound (US) may improve cardiovascular risk (CVR) stratification, especially in intermediate risk population. Our aim was to compare the predictive power of atherosclerotic plaques detected in carotid and femoral arteries by 2-dimensional (2D) vs. 3-dimensional (3D) US for positive coronary artery calcium score (CACS), used as a proxy for CVD, in a middle-aged sample with intermediate 10-year CVR (7.5-20%). METHODS: To detect atherosclerotic plaques by 2D vs. 3D US scan of carotid and femoral arteries and comparison of their association with CACS obtained by computed tomography (CT) of subjects with intermediate CVR belonging to the Aragon Workers' Health Study. RESULTS: 120 men were included, with a 10.4% average 10 years CVR. Forty-one (34.2%) participants had CACS ≥ 1. 90 participants (75%) had at least one plaque detected by 2D scan while 85 participants (70.8%) had at least a plaque detected by 3D US. Conventional CVR estimates c-statistic for CACS was .590. Although the variables most predicted of CACS ≥ 1 were those measured by 3D US (total plaque volume and mean of plaque density, c-statistics: .743 and .750 respectively), their predictive capacity was not statistically significantly different from the number of territories with plaque, measured either by 2D and 3D US (c-statistics .728 to .740 respectively). CONCLUSION: Subclinical atherosclerosis measured by 2D and 3D US were better predictors of CACS ≥ 1 than CVR estimated by conventional guidelines. In our sample, 3D US did not show any significant advantages with respect to 2D US for the prediction of coronary atherosclerosis.

Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence.

BACKGROUND: There is no randomized clinical trials with recurrence of atherosclerotic cardiovascular disease (ASCVD) as a major outcome with rosuvastatin. In order to analyze potential differences in the clinical response to atorvastatin and rosuvastatin in secondary ASCVD prevention, we have analyzed the clinical evolution of those subjects of the Dyslipemia Registry of the Spanish Society of Arteriosclerosis (SEA) who at the time of inclusion in the Registry had already suffered an ASCVD. METHODS: This observational, retrospective, multicenter, national study was designed to determine potential differences between the use of atorvastatin and rosuvastatin in the ASCVD recurrence. Three different follow-up start-times were performed: time of inclusion in the registry; time of first event if this occurred after 2005, and time of first event without date restriction. RESULTS: Baseline characteristics were similar between treatment groups. Among atorvastatin or rosuvastatin users, 89 recurrences of ASCVD were recorded (21.9%), of which 85.4% were coronary. At the inclusion of the subject in the registry, 345 participants had not suffered a recurrence yet. These 345 subjects accumulated 1050 person-years in a mean follow-up of 3 years. Event rates were 2.73 (95% CI: 1.63, 4.25) cases/100 person-years and 2.34 (95% CI: 1.17, 4.10) cases/100 person-years in the atorvastatin and rosuvastatin groups, respectively. There were no statistically significant differences between the two groups independently of the follow-up start-time. CONCLUSIONS: This study does not find differences between high doses of rosuvastatin and atorvastatin in the recurrence of ASCVD, and supports their use as clinically equivalent in secondary prevention of ASCVD.

Metabolic syndrome and insulin resistance are associated with frailty in older adults: a prospective cohort study.

Background: diabetes increases the risk of frailty that is a leading cause of disability and premature mortality in older people. Metabolic syndrome (MS) and insulin resistance (IR) are strong risk factors for diabetes and could, thus, lead to frailty. However, the association between MS or IR and frailty has barely been investigated. Methods: data were obtained from a cohort of 1,499 community-dwelling individuals aged ≥60, who were free of diabetes at 2008-10 and were followed up for 3.5 years. At baseline, MS was ascertained according to the harmonised definition, and IR with the Homoeostatic Model Assessment for IR index (HOMA-IR). Frailty was defined as having three or more of the Fried's criteria: exhaustion, low physical activity, slow walking, unintentional weight loss and low grip strength. Statistical analyses were performed with logistic regression, and adjusted for the main confounders. Results: in 2012, 84 cases of incident frailty were identified. Compared with subjects without MS, those with MS showed increased risk of frailty (multivariate odds ratio [OR]: 1.85; 95% confidence interval [CI] 1.12-3.05). The association persisted after further adjustment for fibrinogen and C-reactive protein. When the frailty criteria were considered individually, low grip strength was the criterion that showed a stronger association with MS (OR: 1.67; 95% CI: 1.25-2.21). Higher HOMA-IR values were also associated with higher risk of frailty. Conclusion: MS and IR were associated with increased risk of frailty. This work extends the spectrum of harmful consequences of MS, and suggests that preventing or controlling MS may serve to delay frailty.

Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study.

BACKGROUND: Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. METHODS AND RESULTS: The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants 40 to 54 years of age (mean age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque or coronary artery calcification ≥1, was classified as focal (1 site affected), intermediate (2-3 sites), or generalized (4-6 sites) after exploration of each vascular site (right/left carotids, aorta, right/left iliofemorals, and coronary arteries). Subclinical atherosclerosis was present in 63% of participants (71% of men, 48% of women). Intermediate and generalized atherosclerosis was identified in 41%. Plaques were most common in the iliofemorals (44%), followed by the carotids (31%) and aorta (25%), whereas coronary artery calcification was present in 18%. Among participants with low Framingham Heart Study (FHS) 10-year risk, subclinical disease was detected in 58%, with intermediate or generalized disease in 36%. When longer-term risk was assessed (30-year FHS), 83% of participants at high risk had atherosclerosis, with 66% classified as intermediate or generalized. CONCLUSIONS: Subclinical atherosclerosis was highly prevalent in this middle-aged cohort, with nearly half of the participants classified as having intermediate or generalized disease. Most participants at high FHS risk had subclinical disease; however, extensive atherosclerosis was also present in a substantial number of low-risk individuals, suggesting added value of imaging for diagnosis and prevention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01410318.

Phthalate exposure and subclinical carotid atherosclerosis: A systematic review and meta-analysis.

Phthalates may be associated with an increased risk of cardiometabolic diseases by interfering with glucose and lipid metabolism and by promoting adipogenesis. This study aimed to perform a systematic review and meta-analysis of the association between phthalate exposure and subclinical carotid atherosclerosis, using surrogate markers such as carotid intima-media thickness (IMT) and carotid plaques. The literature search was performed using four databases (Web of Science, Medline, PubMed, and Scopus), and this systematic review includes all available observational studies until July 6th, 2023. The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias. Meta-analyses were performed, and random effects models were used. Six high-quality cross-sectional studies and 2570 participants aged 12 to 70 were included. Six phthalate metabolites showed significant associations with subclinical carotid atherosclerosis. Exposure to MBzP, ΣDEHP, and MnBP was associated with increased carotid IMT. Exposure to MEP was associated with a higher prevalence of carotid plaques, and MiBP was associated with a lower prevalence. Mixed results were observed for MMP in older adults. The meta-analyses showed a high degree of heterogeneity, and the results are based on single studies. This study accurately describes the evidence of this association to date, suggesting that phthalates are associated with increased carotid IMT and a higher prevalence of carotid plaques. Further research is needed to elucidate this association, as phthalates are still used in the manufacture of everyday products, humans continue to be exposed to them, and atherosclerosis is a public health concern.

Higher Parametric Thyroid Feedback Quantile-based Index is a predictor of type 2 diabetes in a German population sample.

BACKGROUND: Type 2 diabetes has been described to be associated with hypothyroidism but we recently found that a decrease in pituitary sensitivity to thyroid hormone is associated with diabetes, obesity, and the metabolic syndrome.We aim to assess the longitudinal nature of this association in the population-based Study of Health in Pomerania(SHIP) in Germany. MATERIALS AND METHODS: 77% of a population-based sample of 4308 participants between 20 and 79 years was followed for 5 years. We studied 2542 participants without diabetes or thyroid medication at baseline and complete data in the variables of interest. Data of baseline thyroxine(fT4) and thyrotropin(TSH) were used to calculate the Parametric Thyroid Feedback Quantile-based Index(PTFQI), which measures whether TSH remains elevated despite fT4 being high. It uses the average population response as reference. PTFQI association with incidence of type 2 diabetes over 5 years was estimated with Poisson regression models adjusted for age, sex, and body mass index(BMI). RESULTS: Compared with the 1st PTFQI quartile, Incidence Rate Ratios (IRR) for diabetes were 1.54(95% CI 0.97 to 2.46), 1.55(0.94 to 2.57), and 1.97(1.27 to 3.10) for the upper quartiles (p-trend=0.004) after adjusting for age and sex. The association remained statistically significant after additionally adjusting for BMI: 1.64(1.05 to 2.59) for the 4th vs the 1st quartile (p-trend=0.043). CONCLUSIONS: An elevation of the pituitary TSH-inhibition threshold is associated with incident type 2 diabetes independently of BMI. The PTFQI might have clinical potential for prognosis and metabolic status monitoring.

Influence of triglyceride concentration in lipoprotein (a) as a function of dyslipidemia. / Influencia de la concentración de triglicéridos en la lipoproteína(a) en función de la dislipidemia.

BACKGROUND: Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)-TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. PATIENTS AND METHODS: Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. RESULTS: The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0-210) and Lp(a) 55.0 nmol/L (IQR 17.9-156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)-TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300-399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. CONCLUSIONS: Our results show an inverse Lp(a)-TG relationship in TG concentrations > 300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

SEA 2024 Standards for Global Control of Vascular Risk. / Estándares de la Sociedad Española de Arteriosclerosis 2024 para el control global del riesgo vascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to the knowledge, prevention and treatment of vascular diseases, which are the leading cause of death in Spain and entail a high degree of disability and health expenditure. Atherosclerosis is a multifactorial disease and its prevention requires a global approach that takes into account the associated risk factors. This document summarises the current evidence and includes recommendations for patients with established vascular disease or at high vascular risk: it reviews the symptoms and signs to evaluate, the laboratory and imaging procedures to request routinely or in special situations, and includes the estimation of vascular risk, diagnostic criteria for entities that are vascular risk factors, and general and specific recommendations for their treatment. Finally, it presents aspects that are not usually referenced in the literature, such as the organisation of a vascular risk consultation.

The Progression and Early detection of Subclinical Atherosclerosis (PESA) study: rationale and design.

BACKGROUND: The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined. OBJECTIVE: The PESA study examines the presence of subclinical atherosclerosis by means of noninvasive imaging and prospectively analyzes the determinants associated with its development and progression in a middle-aged population. METHODS: The PESA study is an observational, longitudinal and prospective cohort study in a target population of 4000 healthy subjects (40-54 years old, 35% women) based in Madrid (Spain). Recruitment began in June 2010 and will be completed by the end of 2013. Baseline examination consists of (1) assessment for cardiovascular risk factors (including lifestyle and psychosocial factors); (2) screening for subclinical atherosclerosis using 2D/3D ultrasound in carotid, abdominal aorta and iliofemoral arteries, and coronary artery calcium score (CACS) by computed tomography; and (3) blood sampling for determination of traditional risk factors, advanced "omics" and biobanking. In addition, a subgroup of 1300 participants with evidence of atherosclerosis on 2D/3D ultrasound or CACS will undergo a combined (18)F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging ((18)FDG PET/MRI) study of carotid and iliofemoral arteries. Follow-up at 3 and 6 years will include a repetition of baseline measurements, except for the (18)FDG PET/MRI study, which will be repeated at 6 years. CONCLUSIONS: The PESA study is expected to identify new imaging and biological factors associated with the presence and progression of atherosclerosis in asymptomatic people and will help to establish a more personalized management of medical care.

Association between Sugar-Sweetened Beverage Consumption and the Risk of the Metabolic Syndrome: A Systematic Review and Meta-Analysis.

(1) Background: The increasing occurrence of the metabolic syndrome (MetS) is largely related to harmful food habits. Among them, the consumption of sugar-sweetened beverages (SSBs) is noteworthy. However, to our knowledge, there are not enough high-quality methodological studies summarizing the association between the intake of SSBs and the MetS. Therefore, the aim of this study is to examine the existing published results on this association among adults by synthesizing the existing evidence. (2) Methods: Systematic review and meta-analysis of observational studies following the PRISMA guidelines. Relevant information was extracted and presented following the PRISMA recommendations. PubMed and SCOPUS databases were searched for studies published until June 2022 that assessed the association between SSB consumption (including soft drinks, bottled fruit juices, energy drinks, and milkshakes) and the occurrence of MetS. Random effect models were used to estimate pooled odds ratios (ORs) with their 95% coefficient interval, and I2 was used to assess heterogeneity. (3) Results: A total of 14 publications from 6 different countries were included in this meta-analysis (9 cross-sectional and 5 cohort studies). For the cross-sectional studies, which included 62,693 adults, the pooled OR for the risk of MetS was 1.35 (95% CI 1.15, 1.58; I2 57%) when the highest versus the lowest categories of SSB consumption were compared. For the cohort studies, which included 28,932 adults, the pooled OR was 1.18 (95% CI 1.06, 1.32; I2 70%). (4) Conclusions: The consumption of SSBs was positively associated with an increased risk of MetS. The published literature supports public health strategies and the need to reduce the consumption of SSBs to prevent MetS.

Phthalate exposure and the metabolic syndrome: A systematic review and meta-analysis.

Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific phthalate metabolites have been associated with an increased risk of cardiometabolic diseases. The aim of this study was to assess the association between phthalate exposure and the metabolic syndrome in the general population. A comprehensive literature search was performed in four databases (Web of Science, Medline, PubMed, and Scopus). We included all the observational studies that evaluate the association between phthalate metabolites and the metabolic syndrome available until January 31st, 2023. Pooled Odds Ratios (OR) and their 95% confidence intervals were calculated by using the inverse-variance weighted method. Nine cross-sectional studies and 25,365 participants aged from 12 to 80 were included. Comparing extreme categories of phthalate exposure, the pooled ORs for the metabolic syndrome were: 1.08 (95% CI, 1.02-1.16, I2 = 28%) for low molecular weight phthalates, and 1.11 (95% CI, 1.07-1.16, I2 = 7%) for high molecular weight phthalates. For individual phthalate metabolites, the pooled ORs that achieved statistical significance were: 1.13 (95% CI, 1.00-1.27, I2 = 24%) for MiBP; 1.89 (95% CI, 1.17-3.07, I2 = 15%) for MMP in men; 1.12 (95% CI, 1.00-1.25, I2 = 22%) for MCOP; 1.09 (95% CI, 0.99-1.20, I2 = 0%) for MCPP; 1.16 (95% CI, 1.05-1.28, I2 = 6%) for MBzP; and 1.16 (95% CI, 1.09-1.24, I2 = 14%) for DEHP (including ΣDEHP and its metabolites). In conclusion, both low molecular weight and high molecular weight phthalates were associated with an 8 and 11% higher prevalence of the MetS, respectively. The exposure to six specific phthalate metabolites was associated with a higher prevalence of the MetS.

Association of beverage consumption with subclinical atherosclerosis in a Spanish working population.

Beverages play a substantial role meeting water, calorie, and nutrient requirements; however, they are presented as being major contributors to the current obesity epidemic. Although, the relationship between beverage consumption and metabolic risk factors for cardiovascular disease (CVD) in adults has been frequently studied, its association with subclinical atherosclerosis is of increased interest. We studied the association of beverage consumption with the presence of peripheral subclinical atherosclerosis among Spanish workers. We performed a cross-sectional study of 2089 middle-aged males, with a mean age of 50.9 (SD 3.9), and without CVD, carried out in the Aragon Workers' Health Study (AWHS). A food frequency questionnaire was used to measure beverage consumption of low-fat milk, coffee and tea (unsweetened), whole-fat milk, sugar-sweetened beverages, bottled fruit juice, artificially-sweetened beverages and 100% fruit juice. Atherosclerotic plaques were measured by ultrasound (in carotid arteries, and in femoral arteries). Atherosclerotic plaque was defined as a focal structure protruding ≥ 0.5 mm into the lumen, or reaching a thickness ≥ 50% of the surrounding intima-media thickness. As statistical analysis, we use logistic regression models, simultaneously adjusted for all beverage groups. As results, unsweetened coffee was the beverage most associated with peripheral subclinical atherosclerosis with an odds ratio (OR) of 1.25 (1.10-1.41), and 1.23 (1.09-1.40) 100g/day] for carotid, and femoral territories respectively. Moreover, subclinical atherosclerosis was positively associated with whole-fat milk [OR 1.10 (1.02-1.18) 100 g/day] in the femoral territory. The association was protective for low-fat milk in the carotid territory [OR 0.93 (0.88-0.99) 100g/day]. There was also a protective association with bottled fruit juices in the femoral territory [0.84 (0.74-0.94) 100g/day]. Our results suggest a detrimental association with the consumption of coffee, as well as with whole-fat milk and the presence of subclinical atherosclerosis. Therefore, an element of prudence excluding water and low-fat milk, must be applied when recommending beverage consumption.

Low-Quality Carbohydrate Intake Is Associated With a Higher Prevalence of Metabolic Syndrome: The AWHS Study.

CONTEXT: The relationship between carbohydrate quality intake and metabolic syndrome (MetS) is of growing interest. OBJECTIVE: We aimed to assess the association between the adherence to a dietary carbohydrate quality index (CQI) with the occurrence of MetS in a Spanish cohort of working adults. METHODS: A cross-sectional study was conducted of 2316 middle-aged men, aged 50.9 (SD 3.9) years, with no previous cardiovascular disease, and pertaining to the Aragon Workers' Health Study (AWHS) cohort. Diet was collected with a 136-item semiquantitative food-frequency questionnaire. The CQI (range 4-15) was based on: dietary fiber intake, a low glycemic index, the ratio of whole grains/total grains, and the ratio of solid carbohydrates/total carbohydrates. The higher the CQI, the healthier the diet. MetS was defined by using the harmonized National Cholesterol Education Programme-Adult Treatment Panel III (NCEP-ATP III) definition. The associations across 3-point categories of the CQI and the presence of MetS were examined using logistic regression. RESULTS: An inverse and significant association between the CQI and MetS was found. Fully adjusted odds ratios (ORs) for MetS risk among participants in the 10- to 12-point category (second highest CQI category) was 0.64 (95% CI, 0.45-0.94), and in the 13- to 15-point category (highest category) was 0.52 (95% CI, 0.30-0.88), when compared with the 4- to 6-point category (lowest category). Participants with 10 to 12 and 13 to 15 points on the CQI showed a lower risk of hypertriglyceridemia: OR 0.61 (95% CI, 0.46-0.81), and 0.48 (95% CI, 0.32-0.71) respectively. CONCLUSION: Among middle-aged men, a higher adherence to a high-quality carbohydrate diet is associated with a lower prevalence of MetS. Triglyceridemia is the MetS component that contributed the most to this reduced risk.