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INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population-based studies using conventional T2-weighted brain magnetic resonance imaging (MRI) images. METHODS: We included 8420 adults > 40 years old from three longitudinal population-based studies with brain MRI scans. We estimated and meta-analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters > 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13-2.68) and 1.48 (95% CI, 1.12-1.96) fold, respectively. For stroke, meta-analyses yielded HRs of 1.59 (95% CI, 1.04-2.42) for overall arteries and 2.11 (95% CI, 1.45-3.08) for basilar artery diameters > 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.
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Demencia , Accidente Cerebrovascular , Adulto , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Arteria Basilar , Demencia/diagnóstico por imagen , Demencia/epidemiología , Demencia/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND: A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern. METHODS: This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood pressure < 130 mmHg, no antihypertensive drugs, waist-to-hip ratio < 0.95 for women or 1.03 for men, and the absence of diabetes. BMI categories included normal weight, overweight, and obesity (BMI < 25, 25-30, ≥ 30 kg/m2). Participants were classified into six subgroups according to BMI category and metabolic healthy status. Outcomes were fatal and nonfatal composited cardiovascular events. RESULTS: Of 2339 participants, the mean age was 51 years, 1161 (49.6%) were women, 434 (18.6%) had obesity, 117 (5.0%) were classified as MHO, and both cohorts had similar characteristics. Over a median of 9.2-year (3.7-13.0) follow-up, 245 cardiovascular events occurred. Compared to those with metabolically healthy normal weight, individuals with metabolic unhealthy status had a higher risk of cardiovascular events, regardless of BMI category (adjusted HR: 3.30 [95% CI: 1.73-6.28] for normal weight, 2.50 [95% CI: 1.34-4.66] for overweight, and 3.42 [95% CI: 1.81-6.44] for obesity), whereas those with MHO were not at increased risk of cardiovascular events (HR: 1.11 [95% CI: 0.36-3.45]). Factor analysis identified a metabolomic factor mainly associated with glucose regulation, which was associated with cardiovascular events (HR: 1.22 [95% CI: 1.10-1.36]). Individuals with MHO tended to present a higher metabolomic factor score than those with metabolically healthy normal weight (0.175 vs. -0.057, P = 0.019), and the score was comparable to metabolically unhealthy obesity (0.175 vs. -0.080, P = 0.91). CONCLUSIONS: Individuals with MHO may not present higher short-term cardiovascular risk but tend to have a metabolomic pattern associated with higher cardiovascular risk, emphasizing a need for early intervention.
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Enfermedades Cardiovasculares , Obesidad Metabólica Benigna , Masculino , Humanos , Femenino , Persona de Mediana Edad , Obesidad Metabólica Benigna/diagnóstico , Obesidad Metabólica Benigna/epidemiología , Sobrepeso , Factores de Riesgo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Estudios Prospectivos , Encuestas Nutricionales , Índice de Masa Corporal , Obesidad/diagnóstico , Obesidad/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , FenotipoRESUMEN
BACKGROUND: Venezuela is in the throes of a complex humanitarian crisis that is one of the worst in decades to impact any country outside of wartime. This case analysis describes the challenges faced by the ongoing Maracaibo Aging Study (MAS) during the deteriorating conditions in Venezuela. When the MAS began in 1997, it focused on memory-related disorders. Since then, strategic planning and proactive community participation allowed us to anticipate and address logistical, funding, and ethical challenges, and facilitated the enrollment and retention of more than 2500 subjects over 55 years of age. All participants, who are residents of the city of Maracaibo, Venezuela, underwent various assessments on several occasions. Here, we discuss how our approach to implementing a longitudinal, population-based study of age-related conditions has allowed our research program to continue throughout this period of political, economic, and social upheaval. DISCUSSION: As the social context in Venezuela became more complicated, new challenges emerged, and strategies to sustain the study and participation were refined. We identified five main mechanisms through which the evolving humanitarian crisis has affected implementation of the MAS: 1) community dynamics; 2) morale of researchers, staff, and participants; 3) financial feasibility; 4) components of the research process; and 5) impact on the health of staff, participants, and their families. Strategies to compensate for the impact on these components were implemented, based on inputs from community members and staff. Improved communication, greater involvement of stakeholders, broadening the scope of the project, and strengthening international collaboration have been the most useful strategies. Particular demands emerged, related to the increased mortality and comorbidities of participants and staff, and deterioration of basic services and safety. CONCLUSION: Although the MAS has faced numerous obstacles, it has been possible to continue a longitudinal research project throughout the humanitarian crisis, because our research team has engaged the community deeply and developed a sense of mutual commitment, and also because our project has provided funding to help keep researchers employed, somewhat attenuating the brain drain.
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Participación de la Comunidad , Hispánicos o Latinos , Envejecimiento , Humanos , Investigadores , VenezuelaRESUMEN
BACKGROUND: Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. METHODS: UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have ≥5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. EXPECTED OUTCOMES: The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients.
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Hipertensión , Insuficiencia Renal Crónica , Anciano , Presión Sanguínea , Reforma de la Atención de Salud , Humanos , Persona de Mediana Edad , Proteómica , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Late-onset Alzheimer disease (LOAD) is the most common dementia worldwide. APOE-[Latin Small Letter Open E]4 and BIN1 (Bridging Integrator 1) have been implicated in the pathogenesis of this disease, but, although DNA methylation of dinucleotide CpGs in the BIN1 gene influences alterations, it has not been studied in Hispanics. OBJECTIVE: The objective of this study was to evaluate the BIN1 3' intergenic region DNA methylation patterns in a Colombian sample of LOAD patients. METHODS: A case-control study was conducted in 50 individuals with LOAD and 50 age-sex matched controls to determine associations of LOAD with DNA methylation. DNA was isolated from peripheral blood, and methylation levels of 8 CpGs were estimated by bisulfite conversion followed by Sanger sequencing with direct PCR analysis. Logistic regression models adjusted by age, sex, and APOE were used to calculate risk associations between methylation levels and LOAD. RESULTS: Overall, participants with LOAD had significantly lower methylation levels on CpG26 (0.86±0.11 vs. 0.95±0.05; P>0.001), CpG44 (0.84±0.09 vs. 0.94±0.06; P=0.001), and CpG87 (0.64±0.12 vs. 0.82±0.10; P>0.001). Adjusted regression models showed that decreased methylation levels of these CpGs remained as risk factors for LOAD (P<0.05). CONCLUSIONS: Hypomethylation of CpGs in BIN1 might play an important role in the expression of BIN1 and may be a biomarker for identifying individuals at high risk of developing LOAD.
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Proteínas Adaptadoras Transductoras de Señales/genética , Enfermedad de Alzheimer/genética , Metilación de ADN/genética , Fosfatos de Dinucleósidos/genética , Predisposición Genética a la Enfermedad , Proteínas Nucleares/genética , Proteínas Supresoras de Tumor/genética , Anciano , Apolipoproteína E4/genética , Estudios de Casos y Controles , Colombia , Fosfatos de Dinucleósidos/sangre , Femenino , Humanos , Enfermedades de Inicio Tardío/genética , MasculinoRESUMEN
Importance: Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. Objective: To evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and Participants: Longitudinal population-based cohort study of 11â¯135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). Exposures: Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and Measures: Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). Results: Among 11â¯135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and Relevance: In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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Monitoreo Ambulatorio de la Presión Arterial , Enfermedades Cardiovasculares/epidemiología , Hipertensión/complicaciones , Adulto , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea/métodos , Enfermedades Cardiovasculares/etiología , Ritmo Circadiano , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/mortalidad , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the APOE gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls. METHODS: In total, 100 participants were included (71% women; average age, 70 years; range, 43â»91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and APOE methylation. RESULTS: MCI was diagnosed in 41 subjects (average age, 66.5 ± 9.6 years) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (p < 0.05). Higher CpG-227 methylation correlated with lower risk for MCI (p = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = -0.665; p = 0.008). CONCLUSION: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI.
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Apolipoproteínas E/genética , Disfunción Cognitiva/genética , Metilación de ADN/genética , Exones/genética , Adulto , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/sangre , Disfunción Cognitiva/sangre , Islas de CpG/genética , Femenino , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
PURPOSE: To determine which nocturnal blood pressure (BP) parameters (low levels or extreme dipper status) are associated with an increased risk of glaucomatous damage in Hispanics. DESIGN: Observational cross-sectional study. PARTICIPANTS: A subset (n = 93) of the participants from the Maracaibo Aging Study (MAS) who met the study eligibility criteria were included. These participants, who were at least 40 years of age, had measurements for optical tomography coherence, visual field (VF) tests, 24-hour BP, office BP, and intraocular pressure <22 mmHg. METHODS: Univariate and multivariate logistic regression analyses under the generalized estimating equations (GEE) framework were used to examine the relationships between glaucomatous damage and BP parameters, with particular attention to decreases in nocturnal BP. MAIN OUTCOME MEASURES: Glaucomatous optic neuropathy (GON) based on the presence of optic nerve damage and VF defects. RESULTS: The mean age was 61.9 years, and 87.1% were women. Of 185 eyes evaluated, 19 (26.5%) had signs of GON. Individuals with GON had significantly lower 24-hour and nighttime diastolic BP levels than those without. However, results of the multivariate GEE models indicated that the glaucomatous damage was not related to the average systolic or diastolic BP levels measured over 24 hours, daytime, or nighttime. In contrast, extreme decreases in nighttime systolic and diastolic BP (>20% compared with daytime BP) were significant risk factors for glaucomatous damage (odds ratio, 19.78 and 5.55, respectively). CONCLUSIONS: In this population, the link between nocturnal BP and GON is determined by extreme dipping effects rather than low nocturnal BP levels alone. Further studies considering extreme decreases in nocturnal BP in individuals at high risk of glaucoma are warranted.
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Envejecimiento/fisiología , Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Glaucoma de Ángulo Abierto/fisiopatología , Hipotensión/fisiopatología , Enfermedades del Nervio Óptico/fisiopatología , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Estudios Transversales , Femenino , Glaucoma de Ángulo Abierto/diagnóstico , Gonioscopía , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Enfermedades del Nervio Óptico/diagnóstico , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica , Tonometría Ocular , Venezuela , Campos Visuales/fisiologíaRESUMEN
INTRODUCTION: There are few longitudinal studies of dementia in developing countries. We used longitudinal data from the Maracaibo Aging Study to accurately determine the age- and sex-specific incidence of dementia in elderly Latin Americans. METHODS: The Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) was used to diagnose dementia, which was classified as Alzheimer's disease, vascular dementia, or other. Age- and sex-specific incidence was estimated as the number of new cases of dementia divided by person-years (p-y) of follow-up. RESULTS: The incidence of all dementia diagnoses was 9.10 per 1000 p-y (95% confidence interval [CI] 7.13-11.44; 8026 total p-y), 5.18 for Alzheimer's disease (95% CI 3.72-7.03; 7916 total p-y), and 3.35 for vascular dementia (95% CI 2.19-4.91; 7757 total p-y). DISCUSSION: Among Maracaibo Aging Study participants younger than 65 years, the incidence of dementia was higher than that of US Whites. Among individuals older than 65 years, the incidence was comparable to the mean of previous incidence estimates for other populations worldwide.
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Envejecimiento , Demencia/epidemiología , Evaluación Geriátrica , Factores de Edad , Anciano , Anciano de 80 o más Años , Apolipoproteína E4/genética , Planificación en Salud Comunitaria , Demencia/diagnóstico , Demencia/genética , Femenino , Humanos , Incidencia , América Latina/epidemiología , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Glaucoma is one of the leading causes of global blindness and is expected to co-occur more frequently with vascular morbidities in the upcoming years, as both are aging-related diseases. Yet, the pathogenesis of glaucoma is not entirely elucidated and the interplay between intraocular pressure, arterial blood pressure (BP) and ocular perfusion pressure is poorly understood. OBJECTIVES: This systematic review aims to provide clinicians with the latest literature regarding the management of arterial BP in glaucoma patients. METHODS: A systematic search was performed in Medline, Embase, Web of Science and Cochrane Library. Articles written in English assessing the influence of arterial BP and systemic antihypertensive treatment of glaucoma and its management were eligible for inclusion. Additional studies were identified by revising references included in selected articles. RESULTS: 80 Articles were included in this systemic review. A bimodal relation between BP and glaucoma progression was found. Both high and low BP increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the BP over 24 h. CONCLUSIONS: We concluded that systemic BP level associates with glaucomatous damage and provided recommendations for the management and study of arterial BP in glaucoma. Prospective clinical trials are needed to further support these recommendations.
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Presión Arterial , Glaucoma , Humanos , Presión Sanguínea/fisiología , Estudios Prospectivos , Glaucoma/diagnóstico , Glaucoma/tratamiento farmacológico , Glaucoma/epidemiología , Presión IntraocularRESUMEN
[This corrects the article DOI: 10.3389/fcvm.2022.1024044.].
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BACKGROUND: Evidence shows that high 24-h blood pressure (BP) variability increases cardiovascular risk. We investigated whether 24-h BP variability relates to mortality and cardiovascular risk due to inherent variability and/or hypertensive loads in 24-h BP. METHODS: A total of 1,050 participants from the Maracaibo Aging Study (mean age, 66 years; women, 67.2%) underwent 24-h ambulatory BP monitoring and were followed between 2001 and 2016. To evaluate inherent BP variability, we used average real variability (ARV) as it captures variability among consecutive BP readings. 24-h systolic BP load was the proportion (%) of systolic BP readings ≥130 mm Hg during the daytime and ≥110 during the nighttime. Our primary endpoint was total mortality and major adverse cardiovascular endpoints (MACE). Statistics included Cox proportional models. RESULTS: During a median follow-up of 8.3 years, 299 participants died and 210 experienced MACE. Each +2 mm Hg (corresponding to 1-standard deviation) higher 24-h systolic ARV (mean value, 9.0â ±â 2.0 mm Hg) was associated with higher hazard ratios (HRs) for mortality by 1.28-fold (95% confidence interval [CI], 1.14-1.43) and for MACE by 1.24-fold (95% CI, 1.08-1.42). Each 30% higher 24-h systolic BP load (median value, 63%) was associated with mortality and MACE with HRs of 1.29 (95% CI, 1.15-1.46) and 1.28 (95% CI, 1.10-1.48); respectively. After models were additionally adjusted by BP level, only ARV was associated with mortality (HR, 1.17; 95% CI, 1.04-1.33) and MACE (HR, 1.16; 95% CI, 1.00-1.34). CONCLUSIONS: High ARV and hypertensive loads in 24-h systolic BP were associated with mortality and cardiovascular risk, however, only ARV is associated independently of the BP level.
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Enfermedades Cardiovasculares , Hipertensión , Humanos , Femenino , Anciano , Presión Sanguínea/fisiología , Factores de Riesgo , Hipertensión/complicaciones , Monitoreo Ambulatorio de la Presión Arterial , Factores de Riesgo de Enfermedad CardiacaRESUMEN
Cryoablation is a well-established medical procedure for surgically treating atrial fibrillation. Cryothermal catheter therapy induces cellular necrosis by freezing the insides of pulmonary veins, with the goal of disrupting abnormal electrical heart signals. Nevertheless, tissue damage induced by cold temperatures may also lead to other complications after cardiac surgery. In this sense, the simulation of catheter ablation can provide safer environments for training and the performance of cryotherapy interventions. Therefore, in this paper, we propose a novel approach to help better understand how temperature rates can affect this procedure by using computer tools to develop a simulation framework to predict lesion size and determine optimal temperature conditions for reducing the risk of major complications. The results showed that a temperature profile of around -40 °C caused less penetration, reduced necrotic damage, and smaller lesion size in the tissue. Instead, cryotherapy close to -60 °C achieved a greater depth of temperature flow inside the tissue and a larger cross-section area of the lesion. With further development and validation, the framework could represent a cost-effective strategy for providing personalized modeling, better planning of cryocatheter-based treatment, and preventing surgical complications.
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OBJECTIVE: A high office blood pressure (BP) is associated with cognitive decline. However, evidence of 24-h ambulatory BP monitoring is limited, and no studies have investigated whether longitudinal changes in 24-h BP are associated with cognitive decline. We aimed to test whether higher longitudinal changes in 24-h ambulatory BP measurements are associated with cognitive decline. METHODS: We included 437 dementia-free participants from the Maracaibo Aging Study with prospective data on 24-h ambulatory BP monitoring and cognitive function, which was assessed using the selective reminding test (SRT) and the Mini-Mental State Examination (MMSE). Using multivariate linear mixed regression models, we analyzed the association between longitudinal changes in measures of 24-h ambulatory BP levels and variability with cognitive decline. RESULTS: Over a median follow-up of 4 years (interquartile range, 2-5 years), longitudinal changes in 24-h BP level were not associated with cognitive function (Pâ≥â0.09). Higher longitudinal changes in 24-h and daytime BP variability were related to a decline in SRT-delayed recall score; the adjusted scores lowered from -0.10 points [95% confidence interval (CI), -0.16 to -0.04) to -0.07 points (95% CI, -0.13 to -0.02). We observed that a higher nighttime BP variability during follow-up was associated with a decline in the MMSE score (adjusted score lowered from -0.08 to -0.06 points). CONCLUSION: Higher 24-h BP variability, but not BP level, was associated with cognitive decline. Prior to or in the early stages of cognitive decline, 24-h ambulatory BP monitoring might guide strategies to reduce the risk of major dementia-related disorders including Alzheimer's disease.
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BACKGROUND: Intracranial arteriosclerosis could explain the association between blood pressure (BP) and cerebral small vessel disease (CSVD). Therefore, we tested whether intracranial carotid artery calcification (ICAC) mediates the association between BP and CSVD and determined pathophysiological mechanisms based on ICAC subtypes. METHODS: One thousand four hundred fifty-eight stroke-free participants from the Rotterdam Study (mean age, 68 years; 52% women) underwent nonenhanced computed tomography scans to quantify ICAC volume (mm3) between 2003 and 2015. ICAC was categorized into intimal and internal elastic lamina calcifications. CSVD included white matter hyperintensities volume, the presence of lacunes, and cerebral microbleeds visualized on magnetic resonance imaging. Office BP included systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Mediation analysis included a 2-way decomposition to determine the direct association between BP and CSVD and the indirect or mediated effect (negative or positive mediations expressed in %) of log-ICAC volume on such association. RESULTS: BP and log-ICAC were correlated and were also associated with CSVD. In all participants, total log-ICAC volume mediated the association of diastolic BP (-14.5%) and pulse pressure (16.5%) with log-white matter hyperintensities. Internal elastic lamina log-ICAC volume mediated -19.5% of the association between diastolic BP and log-white matter hyperintensities; intimal log-ICAC volume did not mediate associations. For lacunes, total and internal elastic lamina log-ICAC volume mediated the association of diastolic BP (-40% and -45.8%) and pulse pressure (26.9% and 18.2%). We did not observe mediations for cerebral microbleeds. CONCLUSIONS: Intracranial arteriosclerosis mediates the association between BP and CSVD. Internal elastic lamina calcification, considered a proxy of arterial stiffness, is the leading mechanism explaining the link between BP and CSVD.
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Arteriosclerosis , Calcinosis , Enfermedades de las Arterias Carótidas , Enfermedades de los Pequeños Vasos Cerebrales , Arteriosclerosis Intracraneal , Humanos , Femenino , Anciano , Masculino , Presión Sanguínea , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Imagen por Resonancia Magnética , Hemorragia Cerebral , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis/diagnóstico por imagenRESUMEN
AIMS: Coronary artery disease (CAD) is multifactorial, caused by complex pathophysiology, and contributes to a high burden of mortality worldwide. Urinary proteomic analyses may help to identify predictive biomarkers and provide insights into the pathogenesis of CAD. METHODS AND RESULTS: Urinary proteome was analysed in 965 participants using capillary electrophoresis coupled with mass spectrometry. A proteomic classifier was developed in a discovery cohort with 36 individuals with CAD and 36 matched controls using the support vector machine. The classifier was tested in a validation cohort with 115 individuals who progressed to CAD and 778 controls and compared with two previously developed CAD-associated classifiers, CAD238 and ACSP75. The Framingham and SCORE2 risk scores were available in 737 participants. Bioinformatic analysis was performed based on the CAD-associated peptides. The novel proteomic classifier was comprised of 160 urinary peptides, mainly related to collagen turnover, lipid metabolism, and inflammation. In the validation cohort, the classifier provided an area under the receiver operating characteristic curve (AUC) of 0.82 [95% confidence interval (CI): 0.78-0.87] for the CAD prediction in 8 years, superior to CAD238 (AUC: 0.71, 95% CI: 0.66-0.77) and ACSP75 (AUC: 0.53 and 95% CI: 0.47-0.60). On top of CAD238 and ACSP75, the addition of the novel classifier improved the AUC to 0.84 (95% CI: 0.80-0.89). In a multivariable Cox model, a 1-SD increment in the novel classifier was associated with a higher risk of CAD (HR: 1.54, 95% CI: 1.26-1.89, P < 0.0001). The new classifier further improved the risk reclassification of CAD on top of the Framingham or SCORE2 risk scores (net reclassification index: 0.61, 95% CI: 0.25-0.95, P = 0.001; 0.64, 95% CI: 0.28-0.98, P = 0.001, correspondingly). CONCLUSION: A novel urinary proteomic classifier related to collagen metabolism, lipids, and inflammation showed potential for the risk prediction of CAD. Urinary proteome provides an alternative approach to personalized prevention.
A biomarker that can predict coronary artery disease (CAD) is urgently in need. We developed and validated a urinary proteomic classifier for the prediction of CAD. The proteomic classifier involved in atherosclerosis improved the risk reclassification on top of the clinical risk score.
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Enfermedad de la Arteria Coronaria , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Proteómica/métodos , Proteoma/análisis , Proteoma/metabolismo , Biomarcadores , Péptidos , Inflamación , ColágenoRESUMEN
BACKGROUND: Low ocular perfusion pressure (OPP), which depends on the mean arterial pressure (MAP) and intraocular pressure (IOP), is associated with glaucoma. We studied 24-h MAP dysregulations and OPP in relation to the progression of glaucoma damage. METHODS: We retrospectively analyzed 155 normal-tension glaucoma (NTG) and 110 primary open-angle glaucoma (POAG) patients aged 18âyears old followed at the University Hospital Leuven with repeated visual field tests ( n â=â7000 measures, including both eyes) who underwent 24-h ambulatory blood pressure monitoring. Twenty-four-hour MAP dysregulations were variability independent of the mean (VIM), and the five lowest dips in MAP readings over 24âh. OPP was the difference between 2/3 of the MAP and IOP. Glaucoma progression was the deterioration of the visual field, expressed as decibel (dB) changes in mean deviation analyzed by applying multivariable linear mixed regression models. RESULTS: The mean age was 68 years (53% were women). High 24-h VIMmap was associated with glaucoma progression in POAG ( P â<â0.001) independently of the 24-h MAP level. The estimated changes in mean deviation in relation to dip MAP measures ranged from -2.84âdB [95% confidence interval (CI) -4.12 to -1.57] to -2.16âdB (95% CI -3.46 to -0.85) in POAG. Reduced OPP along with high variability and dips in MAP resulted in worse mean deviation deterioration. CONCLUSION: The progression of glaucoma damage associates with repetitive and extreme dips in MAP caused by high variability in MAP throughout 24âh. This progression exacerbates if 24-h MAP dysregulations occur along with reduced OPP.
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Glaucoma de Ángulo Abierto , Humanos , Femenino , Anciano , Adolescente , Masculino , Presión Sanguínea/fisiología , Estudios Retrospectivos , Monitoreo Ambulatorio de la Presión Arterial , Presión Intraocular , PerfusiónRESUMEN
Background: Systemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP. Methods: We conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures. Results: The mean age was 64.0 y (53% women). The median follow-up was 9 years. In adjusted mixed models, functional progression of glaucoma damage was associated with VIMmap (-2.57 dB change in MD per every 3 mmHg increase in VIMmap; P < 0.001) and diurnal MAP dips (changes in the MD ranged from -2.56 to -3.19 dB; P < 0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with -1.14 dB changes in MD [95% confidence interval (CI), -1.90 to -0.40] and 0.01 larger optic disc cupping (95% CI, 0.01-0.02). Lower night-to-day ratio was also related to both outcomes (P ≤ 0.012). Functional glaucoma damage worsened if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP (P ≤ 0.022). Conclusion: Progression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG).