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Lipoprotein(a) Modulates Carotid Atherosclerosis in Metabolic Syndrome.

ABSTRACT: Background and Aim: High lipoprotein(a) [Lp(a)] is a well-established cardiovascular (CV) risk factor, but the effect of mildly elevated Lp(a) on CV health is largely unknown. Our aim was to evaluate if Lp(a) is associated with the severity of carotid atherosclerosis (CA) in the specific subset of metabolic syndrome (MetS). Patients and Methods: Subjects with diagnosed MetS and ultrasound-assessed CA were enrolled. Those patients were categorized according to the severity of CA (moderate vs. severe), and the circulating levels of Lp(a) alongside with clinical, anthropometric, and biochemical data were collected. Results: Sixty-five patients were finally included: twenty-five with moderate and forty with severe CA (all with asymptomatic disease). Intergroup comparison showed Lp(a) as the only significantly different variable [6 (2-12) mg/dl vs. 11.5 (6-29.5) mg/dl; p = 0.018]. Circulating levels of Lp(a) were also confirmed as the only variable independently associated with severity of CA at logistic regression analysis [OR 2.9 (95% CI 1.1-7.8); p = 0.040]. ROC curve analysis for Lp(a) confirmed a serum level of 10 mg/dl as the best cut-off value [AUC 0.675 (95% CI 0.548-0.786)]. Although sensitivity and specificity were suboptimal (69.0 and 70.4%, respectively)-likely due to the small sample size-this result is in line with those previously reported in the literature. Conclusion: Lp(a) is independently associated with severity of CA in the subgroup of MetS patients.

SUBMITTER: Cremonini AL

PROVIDER: S-EPMC9214261 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsTo characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD).Methods and resultsWe used untargeted one-dimensional (1D) serum metabolic profiling by proton nuclear magnetic resonance spectroscopy (1H NMR) among 3867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3569 participants from the Rotterdam and LOLIPOP studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 1H NMR measured metabolites were associated with CAC and/or IMT, P = 1.3 × 10-14 to 1.0 × 10-6 (discovery) and P = 5.6 × 10-10 to 1.1 × 10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched chain, and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine, and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide, and lactate as well as apolipoprotein B (P < 0.05).ConclusionMetabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis.

Project description:BackgroundMetabolic syndrome increases cardiovascular risk. Limited information on its prevalence in Latin America is available. The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study included assessment of metabolic syndrome in 7 urban Latin American populations.MethodsCARMELA was a cross-sectional, population-based, observational study conducted in Barquisimeto, Venezuela; Bogota, Colombia; Buenos Aires, Argentina; Lima, Peru; Mexico City, Mexico; Quito, Ecuador; and Santiago, Chile. The prevalence of metabolic syndrome, defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and associated carotid atherosclerosis were investigated in 11,502 participants aged 25 to 64 years.ResultsAcross CARMELA cities, metabolic syndrome was most prevalent in Mexico City (27%) and Barquisimeto (26%), followed by Santiago (21%), Bogota (20%), Lima (18%), Buenos Aires (17%), and Quito (14%). In nondiabetic participants, prevalence was slightly lower but followed a comparable ranking. Overall, 59%, 59%, and 73% of women with high triglycerides, hypertension, or glucose abnormalities, respectively, and 64%, 48% and 71% of men with abdominal obesity, hypertension, or glucose abnormalities, respectively, had the full metabolic syndrome. Prevalence of metabolic syndrome increased with age, markedly so in women. Mean common carotid artery intima-media thickness (CCAIMT) and prevalence of carotid plaque increased steeply with increasing numbers of metabolic syndrome components; mean CCAIMT was higher and plaque more prevalent in participants with metabolic syndrome than without.ConclusionThe prevalence of metabolic syndrome and its components by NCEP ATP III criteria was substantial across cities, ranging from 14% to 27%. CARMELA findings, including evidence of the association of metabolic syndrome and carotid atherosclerosis, should inform appropriate clinical and public health interventions.

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Lipoprotein(a) Modulates Carotid Atherosclerosis in Metabolic Syndrome.

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