Impact of Lipids and Vascular Damage on Early Atherosclerosis in Adolescents with Parental Premature Coronary Artery Disease.

AIM: To assess the relationship of cardiovascular risk factors (CRFs) with carotid intima media thickness (IMT) in adolescents with a parental history of premature coronary artery disease (PCAD). METHODS: This cross-sectional study included 50 healthy adolescents, aged 14-18 years, both sexes, with a parental history of PCAD, that were compared to 50 controls without this history. Questionnaires regarding information of CRFs were applied. Blood chemistry analyses, included lipid profile, lipoprotein (a), low density lipoprotein (LDL) susceptibility to oxidation, and inflammatory cytokine levels. The IMT was evaluated by ultrasound. RESULTS: The mean age of all participants was 15.9 years. Anthropometric measurements, blood pressure, and lipid profile were similar in both groups. However, the parental history of PCAD group exhibited lower high density lipoprotein cholesterol concentrations, shorter LDL particle oxidation time, and higher lipoprotein (a) levels compared to the control group. IMT was significantly higher in adolescents with a parental history of PCAD compared to controls, (0.53 ± 0.04 mm vs 0.47 ± 0.02 mm, p = 0.001). Among adolescents with a parental history of PCAD, those with ≥ 3 CRFs had significantly higher IMT values (0.56 mm) than those with < 3 CRFs (0.52 mm) and controls (0.48 mm). Multivariable analyses identified that systolic blood pressure and parental history of PCAD explained 26.8% and 16.1% of the variation in IMT. Furthermore, body mass index, LDL-C, ApoB-100, triglycerides and lipoprotein (a) interact with blood pressure levels to explain the IMT values. CONCLUSION: Adolescents with a parental history of PCAD had higher IMT values than the control group, primary explained by systolic blood pressure and the parental inheritance. Adolescents with parental history of PCAD and ≥ 3 CRFs exhibited the highest IMT values. Notably, lipids and systolic blood pressure jointly contribute to explain IMT in these adolescents.

Increased carotid intima-media thickness and cardiometabolic risk factors are associated with IL-6 gene polymorphisms in Mexican individuals: The Genetics of Atherosclerotic Disease Mexican study.

Interleukin 6 (IL-6) is a cytokine implicated in the development of atherosclerosis. This study aimed to determine the association of three IL-6 gene polymorphisms with increased carotid intima-media thickness (CIMT) and cardiometabolic risk factors. Three IL-6 polymorphisms (rs1800795, rs2069827, and rs1800796) were analyzed in 178 individuals with increased CIMT (CIMT ≥ 75th percentile) and 906 individuals without increased CIMT (CIMT < 75th percentile). Logistic regression, adjusted for confounding variables, was employed to assess the associations. The rs1800796 polymorphism was significantly associated with an elevated risk of increased CIMT (OR = 1.354, Padditive = 0.016; OR = 1.803, Precessive = 0.014; OR = 1.989, Pcodominant2 = 0.008). One haplotype (GCG) correlated with a higher risk of increased CIMT (OR = 1.288; P = 0.008), while another (GGG) demonstrated a reduced risk (OR = 0.773; P = 0.006). In individuals without increased CIMT, the rs2069827 polymorphism was associated with low risks of central obesity, hypoalphalipoproteinemia, and a low risk of presenting with high levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C) /HDL-C index, apolipoprotein B, and gamma-glutamyl transpeptidase. The rs1800796 polymorphism was associated with a low risk of adipose tissue insulin resistance, and the rs1800795 was associated with a minimal risk of central obesity and hypoalphalipoproteinemia. Among those with increased CIMT, the rs2069827 was associated with low risks of central obesity, hypertriglyceridemia, metabolic syndrome, and a high triglyceride (TG)/HDL-C index, while rs1800796 was associated with a low risk of fatty liver. Similar IL-6 concentrations were observed in both individuals with and without increased CIMT. In conclusion, the rs1800796 polymorphism is associated with increased CIMT, while the rs2069827 and rs1800795 are linked to cardiovascular risk factors.

Exaggerated blood pressure elevation in response to orthostatic challenge, a post-acute sequelae of SARS-CoV-2 infection (PASC) after hospitalization.

OBJECTIVE: Post-acute sequelae of SARS-COV-2 (PASC) are emerging as a major health challenge. Orthostatic intolerance secondary to autonomic failure has been found in PASC patients. This study investigated the effect of COVID-19 after recovery on blood pressure (BP) during the orthostatic challenge. RESEARCH DESIGN AND METHODS: Thirty-one out of 45 patients hospitalized due to COVID-19-related pneumonia that developed PASC and did not have hypertension at discharge were studied. They underwent a head-up tilt test (HUTT) at 10.8 ± 1.9 months from discharge. All met the PASC clinical criteria, and an alternative diagnosis did not explain the symptoms. This population was compared with 32 historical asymptomatic healthy controls. RESULTS: Exaggerated orthostatic blood pressure response (EOPR)/orthostatic hypertension (OHT) was detected in 8 out of 23 (34.7 %) patients, representing a significantly increased prevalence (7.67-fold increase p = 0.009) compared to 2 out of 32 (6.4 %) asymptomatic healthy controls matched by age, who underwent HUTT and were not infected with SARS-CoV-2. CONCLUSIONS: This prospective evaluation in patients with PASC revealed abnormal blood pressure rise during the orthostatic challenge, suggesting of autonomic dysfunction in a third of the studied subjects. Our findings support the hypothesis that EOPR/OHT may be a phenotype of neurogenic hypertension. Hypertension in PASC patients may adversely affect the cardiovascular burden in the world.

Cardiovascular autonomic responses during head-up tilt test in newly diagnosed type 2 diabetes.

BACKGROUND: Autonomic dysfunction is commonly observed in patients with long-standing type 2 diabetes. Previous studies have confirmed the value of both subjectively assessed symptoms and objective measurements of autonomic nervous system function in diagnosing cardiovascular autonomic neuropathy. However, the head-up tilt test (HUTT) has been rarely used to investigate cardiovascular autonomic responses in subjects with high risk of newly diagnosed type 2 diabetes (nT2D). OBJECTIVE: To evaluate autonomic cardiovascular responses through passive orthostatic challenge along the diabetes continuum. METHODS: The study population was stratified as normoglycemic (n = 16), prediabetes (n = 20), and nT2D (n = 20). The prevalence of orthostatic intolerance and autonomic cardiovascular responses was evaluated with the Task Force Monitor during a 30-min passive HUTT. Spectral indices of heart rate and blood pressure variability and baroreceptor effectiveness index (BEI) were calculated through the HUTT. BEI was obtained by the sequence method. RESULTS: There were no differences in the prevalence of orthostatic intolerance or in the indices of heart rate and blood pressure variability among the three groups of study. The BEI was attenuated in the nT2D group in supine rest and throughout HUTT compared with normoglycemic and prediabetes groups. The multivariable linear regression analysis showed that BEI was associated with fasting glucose (ß = - 0.52, p < 0.001) and HbA1c (ß = - 0.57, p  < 0.001) independently of cardiovascular risk factors. CONCLUSION: Cardiovascular autonomic neuropathy, expressed as blunted BEI, is the only abnormal autonomic nervous test detected in nT2D, and it was independently associated with fasting glucose and HbA1c values.

Post-Acute COVID-19 Symptoms, a Potential Link with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A 6-Month Survey in a Mexican Cohort.

The aim of this study was to describe the clinical evolution during 6 months of follow-up of adults recovered from COVID-19. We tried to determine how many met the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A total of 130 patients (51.0 ± 14 years, 34.6% female) were enrolled. Symptoms were common, participants reported a median number of 9 (IQR 5-14) symptoms. Fatigue was the most common symptom (61/130; 46.9%). Patients with fatigue were older 53.9 ± 13.5 years compared with 48.5 ± 13.3 years in those without fatigue (p = 0.02) and had a longer length of hospital stay, 17 ± 14 days vs. 13 ± 10 days (p = 0.04). There was no difference in other comorbidities between patients with fatigue and those without it, and no association between COVID-19 severity and fatigue. After multivariate adjustment of all baseline clinical features, only age 40 to 50 years old was positively associated with fatigue, OR 2.5 (95% CI 1.05-6.05) p = 0.03. In our survey, only 17 (13%) patients met the Institute of Medicine's criteria for "systemic exertion intolerance disease," the new name of ME/CFS. In conclusion, in some patients, the features of post-acute COVID-19 syndrome overlap with the clinical features of ME/CFS.

Monocyte Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Expression Correlates with cIMT in Mexican Hypertensive Patients. / Expressão de Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade (LRP1) em Monócito em Correlação com EIMC em Pacientes Mexicanos Hipertensos.

BACKGROUND: Arterial hypertension (HTA) represents a major risk factor for cardiovascular morbidity and mortality. It is not yet known which specific molecular mechanisms are associated with the development of essential hypertension. OBJECTIVE: In this study, we analyzed the association between LRP1 monocyte mRNA expression, LRP1 protein expression, and carotid intima media thickness (cIMT) of patients with essential hypertension. METHODS: The LRP1 monocyte mRNA expression and protein levels and cIMT were quantified in 200 Mexican subjects, 91 normotensive (NT) and 109 hypertensive (HT). Statistical significance was defined as p < 0.05. RESULTS: HT patients group had highly significant greater cIMT as compared to NT patients (p=0.002) and this correlated with an increase in the expression of LRP1 mRNA expression (6.54 vs. 2.87) (p = 0.002) and LRP1 protein expression (17.83 vs. 6.25), respectively (p = 0.001). These differences were maintained even when we divided our study groups, taking into account only those who presented dyslipidemia in both, mRNA (p = 0.041) and proteins expression (p < 0.001). It was also found that Ang II mediated LRP1 induction on monocytes in a dose and time dependent manner with significant difference in NT vs. HT (0.195 ± 0.09 vs. 0.226 ± 0.12, p = 0.046). CONCLUSION: An increase in cIMT was found in subjects with hypertension, associated with higher mRNA and LRP1 protein expressions in monocytes, irrespective of the presence of dyslipidemias in HT patients. These results suggest that LRP1 upregulation in monocytes from Mexican hypertensive patients could be involved in the increased cIMT. (Arq Bras Cardiol. 2021; 116(1):56-65).

FUNDAMENTO: A hipertensão arterial (HTA) representa um grande fator de risco de morbidade e mortalidade cardiovascular. Ainda não se sabe que mecanismos moleculares específicos estão associados ao desenvolvimento de hipertensão essencial. OBJETIVO: Neste trabalho, analisamos a associação entre expressão mRNA de monócito LRP1, expressão de proteína LRP1, e espessura íntima-média de carótida (EIMC) de pacientes com hipertensão essencial. MÉTODOS: A expressão mRNA de monócito LRP1 e os níveis de proteína e EIMC foram quantificados em 200 indivíduos mexicanos, sendo 91 normotensos (NT) e 109 hipertensos (HT) A significância estatística foi definida em p < 0,05. RESULTADOS: O grupo de pacientes HT tinha EIMC maior altamente significativa em comparação com os pacientes NT (p = 0,002), e isso está relacionado ao aumento na expressão mRNA de LRP1 (6,54 versus. 2,87) (p = 0,002) e expressão de proteína LRP1 (17,83 versus 6,25), respectivamente (p = 0,001). Essas diferenças foram mantidas mesmo quando dividimos nossos grupos de estudo, levando em consideração apenas aqueles que apresentavam dislipidemia na expressão de mRNA (p = 0,041) e de proteínas (p < 0,001). Também se identificou que a indução de LRP1 mediada por LRP1 em monócitos em de maneira dependente de dose e tempo, com diferença significativa em NT versus HT (0,195 ± 0,09 versus 0,226 ± 0,12, p = 0,046). CONCLUSÃO: Foi encontrado um aumento em EIMC em indivíduos com hipertensão, associada a expressões de proteína LRP1 e mRNA mais altas em monócitos, independente da presença de dislipidemia em pacientes HT. Esses resultados que a upregulation de LRP1 em monócitos de pacientes hipertensos mexicanos poderia estar envolvida na diminuição da EIMC. (Arq Bras Cardiol. 2021; 116(1):56-65).

Expressão de Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade (LRP1) em Monócito em Correlação com EIMC em Pacientes Mexicanos Hipertensos / Monocyte Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Expression Correlates with cIMT in Mexican Hypertensive Patients

Resumo Fundamento A hipertensão arterial (HTA) representa um grande fator de risco de morbidade e mortalidade cardiovascular. Ainda não se sabe que mecanismos moleculares específicos estão associados ao desenvolvimento de hipertensão essencial. Objetivo Neste trabalho, analisamos a associação entre expressão mRNA de monócito LRP1, expressão de proteína LRP1, e espessura íntima-média de carótida (EIMC) de pacientes com hipertensão essencial. Métodos A expressão mRNA de monócito LRP1 e os níveis de proteína e EIMC foram quantificados em 200 indivíduos mexicanos, sendo 91 normotensos (NT) e 109 hipertensos (HT) A significância estatística foi definida em p < 0,05. Resultados O grupo de pacientes HT tinha EIMC maior altamente significativa em comparação com os pacientes NT (p = 0,002), e isso está relacionado ao aumento na expressão mRNA de LRP1 (6,54 versus. 2,87) (p = 0,002) e expressão de proteína LRP1 (17,83 versus 6,25), respectivamente (p = 0,001). Essas diferenças foram mantidas mesmo quando dividimos nossos grupos de estudo, levando em consideração apenas aqueles que apresentavam dislipidemia na expressão de mRNA (p = 0,041) e de proteínas (p < 0,001). Também se identificou que a indução de LRP1 mediada por LRP1 em monócitos em de maneira dependente de dose e tempo, com diferença significativa em NT versus HT (0,195 ± 0,09 versus 0,226 ± 0,12, p = 0,046). Conclusão Foi encontrado um aumento em EIMC em indivíduos com hipertensão, associada a expressões de proteína LRP1 e mRNA mais altas em monócitos, independente da presença de dislipidemia em pacientes HT. Esses resultados que a upregulation de LRP1 em monócitos de pacientes hipertensos mexicanos poderia estar envolvida na diminuição da EIMC. (Arq Bras Cardiol. 2021; 116(1):56-65)

Abstract Background Arterial hypertension (HTA) represents a major risk factor for cardiovascular morbidity and mortality. It is not yet known which specific molecular mechanisms are associated with the development of essential hypertension. Objective In this study, we analyzed the association between LRP1 monocyte mRNA expression, LRP1 protein expression, and carotid intima media thickness (cIMT) of patients with essential hypertension. Methods The LRP1 monocyte mRNA expression and protein levels and cIMT were quantified in 200 Mexican subjects, 91 normotensive (NT) and 109 hypertensive (HT). Statistical significance was defined as p < 0.05. Results HT patients group had highly significant greater cIMT as compared to NT patients (p=0.002) and this correlated with an increase in the expression of LRP1 mRNA expression (6.54 vs. 2.87) (p = 0.002) and LRP1 protein expression (17.83 vs. 6.25), respectively (p = 0.001). These differences were maintained even when we divided our study groups, taking into account only those who presented dyslipidemia in both, mRNA (p = 0.041) and proteins expression (p < 0.001). It was also found that Ang II mediated LRP1 induction on monocytes in a dose and time dependent manner with significant difference in NT vs. HT (0.195 ± 0.09 vs. 0.226 ± 0.12, p = 0.046). Conclusion An increase in cIMT was found in subjects with hypertension, associated with higher mRNA and LRP1 protein expressions in monocytes, irrespective of the presence of dyslipidemias in HT patients. These results suggest that LRP1 upregulation in monocytes from Mexican hypertensive patients could be involved in the increased cIMT. (Arq Bras Cardiol. 2021; 116(1):56-65)

Metabolic control achievement in a population with premature coronary artery disease: results of the genetics of atherosclerotic disease study.

BACKGROUND AND AIMS: To the best of our knowledge, no studies have investigated the metabolic control of patients with premature coronary artery disease (CAD). The present study analyzes the metabolic control, defined as the simultaneous target in blood pressure, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and hemoglobin A1c, as well as the factors associated with its achievement in patients with premature CAD. METHODS: The study included 1206 patients with CAD diagnosed before the age of 55 and 65 years in men and women, respectively. Sociodemographic, clinical and biochemical data were collected to know the prevalence of cardiovascular risk factors, including individual components of metabolic control plus smoking cessation and body mass index (BMI) <25 kg/m2. Non-strict and strict targets were used to evaluate metabolic control. RESULTS: Participants were 54 ± 8 years old, 19.7% were women and had a median CAD evolution of 2.4 years. Non-strict and strict metabolic control was achieved by 18.4% and 6.2% of patients, respectively. Moreover, 79.8% and 67.6% met a composite of three or more cardiovascular risk factor goals using both criteria. BMI <25 kg/m2 was independently associated with 1.734 (95% confidence interval: 1.207-2.492) and 2.541 (95% confidence interval: 1.608-4.014) higher probabilities to meet non-strict or strict metabolic control. CONCLUSION: Our results show that 18.4% and 6.2% of subjects with premature CAD achieved non-strict and strict metabolic control, respectively. BMI <25 kg/m2 was found to be associated with the achievement of metabolic control. Multidisciplinary strategies including healthy lifestyle changes and pharmacological therapies could decrease the socioeconomic and clinical impact of premature CAD.

Association of Adiponectin with Subclinical Atherosclerosis in a Mexican-Mestizo Population.

BACKGROUND AND AIMS: Adiponectin (ADPN) is a cardioprotective adipocytokine, and its association with atherosclerosis development is controversial. The aim of the present study was to assess the association of low ADPN plasma levels with the presence of subclinical atherosclerosis in a Mexican-Mestizo population without history of diabetes or coronary artery disease (CAD). METHODS: In 818 subjects (53.4 ± 9 years; 49.9% women) anthropometry, subcutaneous and visceral adipose tissue, lipids, glucose, C-reactive protein (CRP), insulin, and ADPN levels were determined. Carotid artery intima-media thickness (CIMT) was measured with ultrasound in B mode and the sex-age specific value higher than 75th percentile defined the presence of subclinical atherosclerosis. Low ADPN was considered when plasma concentrations were lower than 25th percentile (8.67 µg/mL in women, 5.30 µg/mL in men). RESULTS: Prevalence of low ADPN was 43.6% (42.9% in women and 44.4% in men; p = 0.66) and elevated CIMT (eCIMT) was 23.8% (25.8% in women and 21.9% in men; p = 0.184). In addition to their higher prevalence of low ADPN, subjects with eCIMT had higher values of body mass index, blood pressure, total cholesterol, triglycerides, glucose, insulin, and CRP. Multivariate analysis revealed that independent of these factors, low ADPN was associated with eCIMT (OR [95% CI]: 1.505 [1.051-2.153]). CONCLUSIONS: In the studied population, low adiponectin concentrations are associated with a higher prevalence of subclinical atherosclerosis, independent of traditional cardiovascular risk factors.

Association of fatty liver with cardiovascular risk factors and subclinical atherosclerosis in a Mexican population.

INTRODUCTION: Individuals with fatty liver (FL) have an increased risk of coronary artery disease (CAD) probably due to its association with cardiometabolic risk factors (CMRF). OBJECTIVE: To know the prevalence of FL and analyze its association with CMRF and subclinical atherosclerosis, in a sample of Mexican Mestizo population. MATERIAL AND METHODS: This study included 846 subjects from the Genetic of Atherosclerosis Disease (GEA) study (53 ± 9 years, 50.7% women) without diabetes and no personal or family history of premature CAD. Blood samples were taken for measurements of lipids profile, uric acid, and insulin. The presence of FL was identified by computed tomography. Carotid intima media thickness (CIMT) was measured by B mode ultrasound, using the > 75 percentile as cutoff value to define subclinical atherosclerosis. RESULTS: The general prevalence of FL was 32.4%. In men, FL was associated with hyperuricemia, whereas in women, hyperuricemia, low level of high density lipoprotein cholesterol, and metabolic syndrome were the factors associated with this hepatic alteration. In women, FL was associated with a 66% higher probability of having high CIMT, independently of age, hypertension, dyslipidemia, and waist circumference, but not of HOMA-IR. CONCLUSIONS: In women, FL was associated with the presence of subclinical atherosclerosis independently of traditional CMRF. Our study suggests that, in women, insulin resistance could be a mediator of metabolic abnormalities and of subclinical atherosclerosis.