RESUMEN
BACKGROUND: Aortic valve calcification (AVC), Lp(a) [lipoprotein(a)], and low-density lipoprotein cholesterol (LDL-C) are associated with severe aortic stenosis (AS). We aimed to determine which of these risk factors were most strongly associated with the risk of incident severe AS. METHODS: A total of 6792 participants from the MESA study (Multi-Ethnic Study of Atherosclerosis) had computed tomography-quantified AVC, Lp(a), and LDL-C values at MESA visit 1 (2000-2002). We calculated the absolute event rate of incident adjudicated severe AS per 1000 person-years and performed multivariable adjusted Cox proportional hazards regression. RESULTS: The mean age was 62 years old, and 47% were women. Over a median 16.7-year follow-up, the rate of incident severe AS increased exponentially with higher AVC, regardless of Lp(a) or LDL-C values. Participants with AVC=0 had a very low rate of severe AS even with elevated Lp(a) ≥50 mg/dL (<0.1/1000 person-years) or LDL-C ≥130 mg/dL (0.1/1000 person-years). AVC >0 was strongly associated with severe AS when Lp(a) <50 mg/dL hazard ratio (HR) of 33.8 (95% CI, 16.4-70.0) or ≥50 mg/dL HR of 61.5 (95% CI, 7.7-494.2) and when LDL-C <130 mg/dL HR of 31.1 (95% CI, 14.4-67.1) or ≥130 mg/dL HR of 50.2 (95% CI, 13.2-191.9). CONCLUSIONS: AVC better identifies people at high risk for severe AS compared with Lp(a) or LDL-C, and people with AVC=0 have a very low long-term rate of severe AS regardless of Lp(a) or LDL-C level. These results suggest AVC should be the preferred prognostic risk marker to identify patients at high risk for severe AS, which may help inform participant selection for future trials testing novel strategies to prevent severe AS.
Asunto(s)
Estenosis de la Válvula Aórtica , Válvula Aórtica , Biomarcadores , Calcinosis , LDL-Colesterol , Lipoproteína(a) , Índice de Severidad de la Enfermedad , Humanos , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/epidemiología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Femenino , Lipoproteína(a)/sangre , Masculino , Persona de Mediana Edad , LDL-Colesterol/sangre , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Calcinosis/sangre , Calcinosis/diagnóstico por imagen , Calcinosis/diagnóstico , Calcinosis/epidemiología , Calcinosis/etnología , Anciano , Biomarcadores/sangre , Factores de Riesgo , Medición de Riesgo , Incidencia , Estados Unidos/epidemiología , Anciano de 80 o más Años , Valor Predictivo de las Pruebas , Factores de Tiempo , Estudios Prospectivos , Modelos de Riesgos Proporcionales , Tomografía Computarizada por Rayos X , PronósticoRESUMEN
Mitral annular calcification (MAC) may be a potential marker of biologic aging. However, the association of MAC with noncardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and noncardiovascular mortality, is not well-studied in a multiracial cohort. We used data from 6,814 participants (mean age: 62.2 ± 10.2 years, 52.9% women) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with noncontrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed the cross-sectional association of MAC with BMD and walking pace. Furthermore, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. In addition, we assessed the association of MAC with cardiovascular and noncardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient -0.04, 95% confidence interval [CI] -0.06 to -0.02), with significant interaction by gender (p-interaction = 0.035). MAC was, however, not associated with impaired walking pace (odds ratio 1.09, 95% CI 0.89 to 1.33). Compared with participants without MAC, those with MAC had an increased risk of incident renal failure, albeit nonsignificant (hazard ratio [HR] 1.18, 95% CI 0.95 to 1.45), and a significantly higher hazards of dementia (HR 1.36, 95% CI 1.10 to 1.70). In addition, participants with MAC had a substantially higher risk of all-cause (HR 1.47, 95% CI 1.29 to 1.69), cardiovascular (subdistribution HR 1.39, 95% CI 1.04 to 1.87), and noncardiovascular mortality (subdistribution HR 1.35, 95% CI 1.14 to 1.60) than those without MAC. MAC ≥100 versus <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and noncardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia and all-cause, cardiovascular, and noncardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of noncardiovascular outcomes and death from other causes.
Asunto(s)
Válvula Mitral , Humanos , Femenino , Masculino , Válvula Mitral/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Calcinosis/diagnóstico por imagen , Calcinosis/epidemiología , Calcinosis/etnología , Estados Unidos/epidemiología , Aterosclerosis/etnología , Demencia/epidemiología , Densidad Ósea , Enfermedades de las Válvulas Cardíacas/epidemiología , Enfermedades de las Válvulas Cardíacas/complicaciones , Tomografía Computarizada por Rayos X , Etnicidad/estadística & datos numéricos , Insuficiencia Renal/epidemiología , Estudios Transversales , Factores de Riesgo , Prevalencia , Incidencia , Velocidad al Caminar , Enfermedades Cardiovasculares/etnología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Causas de Muerte/tendenciasRESUMEN
The association of self-reported BMI at age 20, at age 40, the highest BMI within the past 3 years, and current BMI with current mid-life cardiovascular risk factors and coronary artery calcium (CAC) was evaluated among 1148 South Asian American participants (mean age 57 years) in the MASALA study. A 1 kg/m2 higher BMI at age 20 was associated with higher odds of hypertension (aOR 1.07, 95% CI 1.03-1.12), pre-diabetes/diabetes (aOR 1.05 [1.01-1.09]), and prevalent CAC (aOR 1.06 [1.02-1.11]) in mid-life. Associations were similar for all BMI measures. Weight across young adulthood is associated with mid-life cardiovascular health in South Asian American adults.
Asunto(s)
Índice de Masa Corporal , Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Personas del Sur de Asia , Adulto , Humanos , Persona de Mediana Edad , Adulto Joven , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo , Estados Unidos/epidemiología , Personas del Sur de Asia/estadística & datos numéricos , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etnología , Calcinosis/epidemiología , Calcinosis/etnología , Sur de Asia/etnologíaRESUMEN
Aims: Anecdotal reports have suggested increased soft tissue calcification in individuals with long-term exposures to high blood glucose. The association of costal cartilage calcification (CCC), a reliably quantifiable marker obtainable from non-contrast cardiac computed tomography (CT) with cumulative fasting blood glucose (FBG) exposure, is unknown. In this study, we aimed to determine the association between quantified CCC and cumulative glucose exposure using non-contrast coronary artery calcium (CAC) scoring computed tomography (CT) images in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The volume of bilateral CCC was quantified in high-density pixels (threshold of Hounsfield Unit>180) using the CAC scoring CT images acquired in the 5th MESA exam. Prior long-term cumulative exposure to FBG was calculated by area under the FBG-time curve over ten years before the time of the CT exam. Results: A total of 2,305 participants (mean age: 69, female/male: 1.3) were included in this study. The median CCC volume was lower in females than males (1158 mm3 [IQR: 1751] vs. 3054 mm3 [3851], p<0.001). In cross-sectional analysis, quantified CCC was associated with FBG (9% increase per SD) and HbA1c (7% increase per SD) at the CT exam only in female participants after adjustment for age, race, BMI, and glomerular filtration rate. Only in female participants, quantified CCC was also associated with prior cumulative FBG (3% increase per decile change). In the subgroup of females with zero CAC scores, the adjusted CCC was still associated with FBG (13% increase per SD) at the time of CT exam and with prior cumulative FBG exposure (4% increase per decile change) before the CT exam. Conclusions: The CCC, a reliably quantified marker in non-contrast cardiac CT, is associated with 10-year cumulative FBG exposure only in female participants, even those with zero CAC.
Asunto(s)
Aterosclerosis/diagnóstico por imagen , Aterosclerosis/etnología , Glucemia/metabolismo , Calcinosis/diagnóstico por imagen , Calcinosis/etnología , Cartílago Costal/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Aterosclerosis/sangre , Calcinosis/sangre , Estudios de Cohortes , Cartílago Costal/metabolismo , Estudios Transversales , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The early stages of aortic valve calcification (AVC) and coronary artery calcification (CAC) include shared ASCVD risk factors, yet there is considerable heterogeneity between the burden of AVC, and CAC. We sought to identify the markers associated with limited CAC among persons with significant AVC. There were 325 participants from the Multi-Ethnic Study of Atherosclerosis without clinical ASCVD and with AVC ≥100 Agatston units (AU) at Visit 1. Multivariable-adjusted prevalence ratios for limited CAC (0 to 99 AU) were calculated using modified Poisson regression. Participants had a mean age of 72.1 years, median AVC score of 209, and 34% were women. A total of 133 (41%) participants had CAC <100, of whom 46/133 had CAC = 0. Younger age (PR = 1.40, 95% CI: 1.22 to 1.62, per 10-years), female gender (PR = 1.68, 95% CI: 1.28 to 2.20), and low 10-year ASCVD risk (PR = 2.30, 95% CI: 1.85 to 2.85) were most strongly associated with limited CAC. Neither a normal lipoprotein(a) nor normal measures of inflammation were significantly associated with limited CAC. Lower serum phosphate (PR = 1.15, 95% CI: 1.01 to 1.31; per 0.5 mg/dl lower) and calcium-phosphate product (PR = 1.16, 95% CI: 1.02 to 1.34; per SD lower) were associated with an approximately 15% higher prevalence of limited CAC. In conclusion, more than 40% of persons with significant AVC had CAC. Beyond traditional risk factors, lower serum phosphate, and lower calcium-phosphate product were associated with a higher prevalence of limited CAC.
Asunto(s)
Estenosis de la Válvula Aórtica/etnología , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Calcinosis/etnología , Enfermedad de la Arteria Coronaria/etnología , Vasos Coronarios/diagnóstico por imagen , Etnicidad , Medición de Riesgo/métodos , Calcificación Vascular/etnología , Anciano , Anciano de 80 o más Años , Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico , Calcinosis/complicaciones , Calcinosis/diagnóstico , Calcio/metabolismo , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Vasos Coronarios/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X , Estados Unidos/epidemiología , Calcificación Vascular/complicaciones , Calcificación Vascular/diagnósticoRESUMEN
BACKGROUND: Lipoprotein (a) [Lp(a)] is a risk factor for coronary heart disease and calcific aortic valve disease. We determined the relationships of Lp(a) with prevalence and progression of coronary artery calcification (CAC), mitral annular calcification (MAC), and thoracic aortic calcification (TAC) in a multi-ethnic cohort of middle to older-aged adults. METHODS: This analysis included 6705 Multi-Ethnic Study of Atherosclerosis participants. Lp(a) was measured with a turbidimetric immunoassay. CAC, MAC, and TAC were assessed by cardiac computed tomography both at baseline and once during follow-up. RESULTS: In adjusted relative risk regression cross-sectional analysis, a Lp(a) level ≥50 âmg/dL was associated with a 22% higher prevalence of MAC (relative risk (RR) â= â1.22, 95% confidence interval (CI) 1.00, 1.49). No significant associations were observed for prevalent CAC or TAC. In adjusted prospective analyses, participants with Lp(a) ≥50 âmg/dL were at significantly higher risk for rapid CAC progression (median follow-up â= â8.9 years), defined as ≥100 units/year, compared to those with lower Lp(a) levels (RR â= â1.67, 95% CI â= â1.23, 2.27). The association between higher Lp(a) levels and incident CHD was no longer significant after adjusting for CAC progression. No significant associations were observed for MAC or TAC progression (median follow-up â= â2.6 years). CONCLUSIONS: Higher Lp(a) levels are associated with more rapid CAC progression. Additional study is needed to better understand how this relationship can further improve the ability of Lp(a) to enhance cardiovascular disease risk prediction.
Asunto(s)
Aorta Torácica , Enfermedades de la Aorta/sangre , Calcinosis/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedades de las Válvulas Cardíacas/sangre , Lipoproteína(a)/sangre , Válvula Mitral , Calcificación Vascular/sangre , Anciano , Anciano de 80 o más Años , Aorta Torácica/diagnóstico por imagen , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/etnología , Biomarcadores/sangre , Calcinosis/diagnóstico por imagen , Calcinosis/etnología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/etnología , Estudios Transversales , Femenino , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/etnología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Prevalencia , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiología , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/etnologíaRESUMEN
Aortic stenosis (AS) is common and increasing in prevalence as the population ages. Using computed tomography (CT) to quantify aortic valve calcification (AVC) it has been reported that men have greater degrees of calcification than women among subjects with severe AS. These data, however, were derived in largely Caucasian populations and have not been verified in non-Caucasian subjects. This retrospective study identified 137 patients with severe AS who underwent valve replacement and had CT scans within 6 months prior to surgery. AVC scores were compared between men and women, both in the entire sample and in racial subgroups. 52% of subjects were male and 62.8% were non-Caucasian. Mean AVC score for the entire cohort was 3062.08±2097.87 with a range of 428-13,089. Gender differences in aortic valve calcification were found to be statistically significant with an average AVC score of 3646±2422 in men and 2433±1453 in women (p=0.001). On multivariate analysis, gender remained significantly associated with AVC score both in the entire sample (p=0.014) and in the non-Caucasian subgroup (p=0.008). Mean AVA was significantly greater in males than females but this difference disappeared when AVA was indexed to BSA (p=0.719). AVA was not different between racial groups (p=0.369). In this research we observed that among subjects with severe AS men have higher AVC scores than women regardless of racial background. This is consistent with previous studies in predominantly Caucasian populations.
Asunto(s)
Estenosis de la Válvula Aórtica/patología , Válvula Aórtica/patología , Calcinosis/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/epidemiología , Estenosis de la Válvula Aórtica/etnología , Estenosis de la Válvula Aórtica/cirugía , Calcinosis/complicaciones , Calcinosis/etnología , Comorbilidad , Ecocardiografía/normas , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Caracteres Sexuales , Tomografía Computarizada por Rayos X/métodosRESUMEN
Aldosterone is a steroid hormone regulating fluid and electrolyte homeostasis and is known to increase the risk of atherosclerosis. In this study, we examined the associations of serum aldosterone concentrations with subclinical atherosclerosis and all-cause mortality. This study included 948 adults aged 46 to 88 years from the MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity and not taking antihypertensive medications. Coronary calcification was longitudinally assessed using Agatston coronary artery calcium score from computed tomography scans. All-cause mortality was ascertained from the medical record. The average age (SD) was 62.3 (9.4) years and 53% were male. Among 700 subjects who had follow-up coronary artery calcium score (median follow-up of 6.4 years), higher aldosterone levels (per 100 pg/mL) were associated with higher coronary artery calcium (relative ratio, 1.17 [95% CI, 1.04-1.32]), with the association being stronger in individuals with suppressed plasma renin activity (≤0.5 µg/L/hr). Systolic or diastolic blood pressure mediated around 45% of the total effect of aldosterone on coronary artery calcium. Over a median follow-up of 12.5 years (120 deaths identified among 948 subjects), aldosterone was associated with the increased risk of all-cause mortality when plasma renin activity was suppressed; hazard ratio per 100 pg/mL, 1.70 (95% CI, 1.10-2.63). In this study, we found that higher aldosterone levels were associated with the increased risk of subclinical coronary atherosclerosis and all-cause mortality particularly when renin was suppressed. Our findings indicate the importance of aldosterone levels (even within the reference range) with respect to the cardiovascular system and overall health.
Asunto(s)
Aldosterona/sangre , Presión Sanguínea , Calcinosis/metabolismo , Calcio/análisis , Enfermedad de la Arteria Coronaria/metabolismo , Vasos Coronarios/química , Anciano , Anciano de 80 o más Años , Calcinosis/sangre , Calcinosis/etnología , Calcinosis/fisiopatología , Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etnología , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Estudios Prospectivos , Renina/sangre , Factores SocioeconómicosRESUMEN
OBJECTIVE: Ultraviolet (UV) radiation is considered to be an important environmental factor in the clinical course of children with juvenile dermatomyositis (DM). We aimed to evaluate the association between UV radiation and severe disease outcomes in juvenile DM. METHODS: This is a cross-sectional study of patients with juvenile DM enrolled in the US multicenter Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry from 2010 to 2015. The mean UV index (UVI) in the calendar month prior to symptom onset in each subject's zip code was calculated from daily satellite solar noon measurements. Multivariable logistic regression was used to model the relationship between the mean UVI and calcinosis as well as other outcomes of severe disease. Covariates included sex, race, age, time to diagnosis, disease duration, and latitude. RESULTS: In a multivariable model, there was no association between the mean UVI and calcinosis. African American race was associated with a 3-fold greater odds of calcinosis. However, there was a significant statistical interaction between race and mean UVI. Accounting for this interaction, the odds of calcinosis markedly decreased in African American subjects and steadily increased in non-African American subjects over a range of increasing the mean UVI. Higher mean UVI was associated with decreased odds of using biologics or nonmethotrexate disease-modifying antirheumatic drugs and skin ulceration. CONCLUSION: We described a novel association between UV radiation, calcinosis, and race in a large cohort of patients with juvenile DM. This study furthers our knowledge of the role of UV radiation in the clinical course of juvenile DM and highlights the complex interplay between genes and environment in the clinical phenotypes and development of calcinosis in children with juvenile DM.
Asunto(s)
Dermatomiositis/diagnóstico , Exposición a Riesgos Ambientales/efectos adversos , Sistema de Registros , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Calcinosis/diagnóstico , Calcinosis/etnología , Calcinosis/etiología , Niño , Preescolar , Estudios Transversales , Dermatomiositis/etnología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Pronóstico , Estudios Retrospectivos , Reumatología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Piel/patología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND AIMS: Aortic valve calcification (AVC) may be associated with atherogenic processes arising from endothelial dysfunction (ED). Limited data is available about the relationship between ED, defined by flow mediated dilation (FMD%) and biomarkers, and the prevalence and progression of AVC in a multiethnic population. METHODS: A sample of 3475 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with both initial and repeat CT scans at a mean of 2.65⯱â¯0.84 years and FMD% and serologic markers of ED [ C-reactive protein (CRP), Von Willebrand factor (vWF), Plasminogen Activator Inhibitor (PAI), fibrinogen, Interleukin 6 (IL6), E-selectin and ICAM-1 (Intercellular Adhesion Molecule 1)], were analyzed. Multivariate modeling evaluated the association between ED and the prevalent AVC and AVC progression. RESULTS: The median levels of FMD% was lower and vWF%, fibrinogen, IL6 and ICAM-1 were significantly higher in the AVC prevalence group versus no AVC prevalence (all pâ¯<â¯0.001). In the fully adjusted model for established risk factors, decreasing FMD% or increasing biomarkers was not independently associated with AVC prevalence [OR FMD% 1.028 (0.786, 1.346), CRP 0.981 (0.825, 1.168), vWF 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 1.116 (0.424, 2.940), IL6 1.065 (0.779, 1.456), E-selectin 0.876 (0.479, 1.602) and ICAM-1 1.766 (0.834, 3.743)]. In the AVC progression group, FMD%, vWF%, fibrinogen and IL6 were significantly different (pâ¯<â¯0.05). After adjusting for cardiac risk factors, AVC progression was not independently associated with decreasing FMD% or increasing biomarkers [OR FMD% 1.105 (0.835, 1.463), CRP 1.014 (0.849, 1.210), vWF% 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 0.909 (0.338, 2.443), IL6 1.061 (0.772, 1.459), E-selectin 0.794 (0.426, 1.480) and ICAM-1 0.998 (0.476, 2.092)]. CONCLUSIONS: Endothelial dysfunction by FMD% and biomarkers is not significantly associated with the prevalence or progression of aortic valve calcification after adjustment for cardiac risk factors.
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Estenosis de la Válvula Aórtica/fisiopatología , Válvula Aórtica/patología , Aterosclerosis/fisiopatología , Calcinosis/fisiopatología , Anciano , Anciano de 80 o más Años , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/etnología , Aterosclerosis/complicaciones , Aterosclerosis/etnología , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Calcinosis/complicaciones , Calcinosis/etnología , Progresión de la Enfermedad , Selectina E/análisis , Endotelio Vascular/fisiopatología , Etnicidad , Femenino , Fibrinógeno/análisis , Humanos , Molécula 1 de Adhesión Intercelular/análisis , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Estudios Prospectivos , Factores de RiesgoRESUMEN
RATIONALE: Pantothenate kinase-associated neurodegeneration (PKAN) represents an autosomal recessive hereditary disease. In this report, a PANK2 gene mutation in a Chinese child was identified, as well as detections of PKAN among his family members. Our findings exposed a world-wide novel compound heterozygous mutation. PATIENT CONCERNS: We described a 6-year-old male patient with PKAN, exhibiting involuntary movement for a period of 1.5 years, as well as feeding difficulties for 2 weeks. DIAGNOSIS: Due to brain computed tomography and magnetic resonance imaging results, and patient behavior, the attending physician suspected a hereditary effect. INTERVENTIONS: The patient sample underwent high-throughput sequencing. Subsequently, his parents and sister were screened for the mutations identified in the patient genome. OUTCOMES: High-throughput sequencing revealed a novel complex heterozygous mutation of the PANK2 gene, which was detected in the second and fourth exons, c.A650G, and c.T1341G, respectively, resulting in amino acid alterations (p.D217G and p.D447E, respectively). The child's father was confirmed to possess a heterozygous c.A650G mutation, while his mother was heterozygous for the c.T1341G mutation. LESSONS: The key finding of the study encompassed the detection of a novel PANK2 gene mutation in a child of Chinese ethnicity with PKAN. The PANK2 gene c.A650G, as well as c.T1341G, mutations may be potential mutation hotspots in children with PKAN in Mainland China.
Asunto(s)
Enfermedades de los Ganglios Basales/genética , Calcinosis/genética , Análisis Mutacional de ADN , Tamización de Portadores Genéticos , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Enfermedades de los Ganglios Basales/diagnóstico , Enfermedades de los Ganglios Basales/etnología , Calcinosis/diagnóstico , Calcinosis/etnología , Niño , China , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, < median values (low), and ≥ median values (high) for patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.
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Estenosis de la Válvula Aórtica/fisiopatología , Válvula Aórtica/patología , Aterosclerosis/etnología , Calcinosis/fisiopatología , Etnicidad , Estenosis de la Válvula Mitral/fisiopatología , Capacitancia Vascular/fisiología , Población Blanca , Adulto , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/etnología , Aterosclerosis/fisiopatología , Calcinosis/diagnóstico por imagen , Calcinosis/etnología , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estenosis de la Válvula Mitral/diagnóstico por imagen , Estenosis de la Válvula Mitral/etnología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Long-term exposure to high ambient air pollution has been associated with coronary artery calcium (CAC), a marker of cardiovascular disease (CVD). Calcifications of left-sided heart valves are also markers of CVD risk. We investigated whether air pollution was associated with valvular calcification and its progression. METHODS: We studied 6253 MESA participants aged 45-84 years who underwent two cardiac CT scans 2.5 years apart to quantify aortic valve calcium (AVC) and mitral annular calcium (MAC). CAC was included for the same timeframe for comparison with AVC/MAC. Ambient particulate matter <2.5 µm (PM2.5) and oxides of nitrogen (NOx) concentrations were predicted from residence-specific spatio-temporal models. RESULTS: The mean age (SD) of the study sample was 62 (10) years, 39% were white, 27% black, 22% Hispanic, and 12% Chinese. The prevalence of AVC and MAC at baseline were 13% and 9% respectively, compared to 50% prevalence of CAC. The adjusted prevalence ratios of AVC and MAC for each 5 µg/m3 higher PM2.5 was 1.19 (95% CI 0.87, 1.62) and 1.20 (0.81, 1.77) respectively, and for CAC was 1.14 (1.01, 1.27). Over 2.5 years, the mean change in Agatston units/year for each 5 µg/m3 higher PM2.5 concentration was 0.29 (-5.05, 5.63) for AVC and 4.38 (-9.13, 17.88) for MAC, compared to 8.66 (0.61, 16.71) for CAC. We found no significant associations of NOx with AVC and MAC. CONCLUSION: Our findings suggest a trend towards increased 2.5-year progression of MAC with exposure to outdoor PM2.5, although this association could not be confirmed. Additional well-powered studies with longer periods of follow-up are needed to further study associations of air pollution with valvular calcium. TRIAL REGISTRATION: Although MESA is not a clinical trial, this cohort is registered at ClinicalTrials.gov Identifier: NCT00005487; Date of registration May 25, 2000.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Calcinosis/etiología , Exposición a Riesgos Ambientales/efectos adversos , Enfermedades de las Válvulas Cardíacas/etiología , Válvula Mitral/efectos de los fármacos , Material Particulado/efectos adversos , Anciano , Anciano de 80 o más Años , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/efectos de los fármacos , Aterosclerosis , Calcinosis/diagnóstico por imagen , Calcinosis/etnología , Exposición a Riesgos Ambientales/análisis , Femenino , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/etnología , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Óxidos de Nitrógeno/análisis , Material Particulado/análisis , Grupos Raciales , Tomografía Computarizada por Rayos XRESUMEN
Serum 25-hydroxyvitamin D [25(OH)D] concentration has been identified as a possible modifiable risk factor for cardiovascular disease (CVD). We hypothesized that serum 25(OH)D concentration would be associated with calcifications of the left-sided heart valves, which are markers of CVD risk. Aortic valve calcium (AVC) and mitral annular calcium (MAC) were quantified from cardiac computed tomography scans performed on 5,530 Multi-Ethnic Study of Atherosclerosis participants at the baseline examination (2000 to 2002) and at a follow-up visit at either Examination 2 (2002 to 2004) or Examination 3 (2004 to 2005). 25(OH)D was measured from serum samples collected at the baseline examination. Using relative risk regression, we evaluated the multivariable-adjusted risk of prevalent and incident AVC and MAC in this ethnically diverse population free of clinical CVD at baseline. The mean age of participants was 62 ± 10 years; 53% were women, 40% white, 26% black, 21% Hispanic, and 12% Chinese. Prevalent AVC and MAC were observed in 12% and 9% of study sample, respectively. There were no significant associations between 25(OH)D and prevalent AVC or MAC. Over a mean follow-up of 2.5 years, 4% developed incident AVC and 5% developed incident MAC. After adjusting for demographic variables, each 10 ng/ml higher serum 25(OH)D was associated with a 15% (relative risk 0.85, 95% confidence interval 0.74 to 0.98) lower risk of incident MAC but not AVC. However, this association was no longer significant after adjusting for lifestyle and CVD risk factors. Results suggest a possible link between serum 25(OH)D and the risk for incident MAC, but future studies with longer follow-up are needed to further test this association.
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Válvula Aórtica/diagnóstico por imagen , Aterosclerosis/sangre , Calcinosis/etiología , Etnicidad , Enfermedades de las Válvulas Cardíacas/etiología , Válvula Mitral/diagnóstico por imagen , Vitamina D/análogos & derivados , Anciano , Anciano de 80 o más Años , Aterosclerosis/etnología , Aterosclerosis/metabolismo , Calcinosis/etnología , Calcinosis/metabolismo , Calcio/metabolismo , Femenino , Estudios de Seguimiento , Enfermedades de las Válvulas Cardíacas/etnología , Enfermedades de las Válvulas Cardíacas/metabolismo , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X , Estados Unidos/epidemiología , Vitamina D/sangreRESUMEN
We assessed the relationships among adult height, coronary artery calcium (CAC) score, incident atherosclerotic cardiovascular disease (ASCVD) events, and atrial fibrillation (AFib) in a multiethnic cohort. We used race/ethnicity-specific height (dichotomized by median value and in quartiles) as the predictor variable within the 4 racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (n = 6,814). After a mean of 10.2 years of follow-up (2000-2012), 556 ASCVD events (8.2%) and 539 AFib events (7.9%) occurred. Adult height was not associated with prevalent CAC score (ln(CAC + 1) or categories). Tall stature (i.e., race/ethnicity-specific height ≥median) had a significant but opposite association with future ASCVD and AFib (hazard ratios were 0.72 (95% confidence interval: 0.56, 0.92) and 1.38 (95% confidence interval: 1.07, 1.79), respectively). We observed a gradient-response but opposite association between quartiles of race/ethnicity-specific height and ASCVD/AFib events in our multivariable models. A formal test of interaction between race/ethnicity-specific height and sex was not significant in the ASCVD model (P = 0.78) but was significant in the AFib model (P = 0.03). Tall stature was associated (in a gradient-response fashion) with reduced risk of ASCVD events and increased risk of AFib. Adult height may signal interactions between genetic and environmental factors and may provide risk information independent of current traditional risk factors and CAC score.
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Fibrilación Atrial/etnología , Estatura/etnología , Enfermedad de la Arteria Coronaria/etnología , Anciano , Anciano de 80 o más Años , Calcinosis/etnología , Estudios de Cohortes , Vasos Coronarios/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
Calcinosis is a frequent complication of systemic sclerosis (SSc) that is usually located in extremities but may occur across the board. The aim of our study was to identify and quantify the distribution of calcinosis in a cohort of Mexican patients with SSc and its association with clinical features and autoantibodies. A cohort of patients with SSc (2013 ACR/EULAR criteria), classified in diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) (Le Roy criteria), was studied. For their analysis, patients were allocated into those with and without calcinosis (clinical and/or radiological). The evaluation included the modified Rodnan scale for skin and Medsger disease severity scale (DSS). Calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) and antinuclear antibodies and extractable nuclear antigens were determined in serum. A total of 109 patients were included, 41 (37 %) with and 68 (63 %) without calcinosis. Calcinosis was more frequent in patients with dcSSc (55 vs 27 %). In total, we identified 354 sites with calcinosis and mean per patient of 12.0 ± 9.1; the most common sites affected were the hands (83 %), proximal upper extremity (27 %), and proximal lower extremity (22 %). Patients with calcinosis had a higher score of Rodnan scale, Mesdger DSS, and frequency of anti-nucleolar and anti-Scl-70 antibodies compared to those without calcinosis. Abnormal PTH elevation was found in 35 % of patients with calcinosis and 23 % without it. The prevalence of calcinosis is high in Mexican patients with SSc, especially in diffuse variety, and is associated with increased severity of disease.
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Calcinosis/sangre , Calcinosis/diagnóstico por imagen , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/diagnóstico por imagen , Adulto , Anticuerpos Antinucleares/sangre , Calcinosis/complicaciones , Calcinosis/etnología , Calcio/sangre , Femenino , Células Hep G2 , Humanos , Masculino , México , Persona de Mediana Edad , Análisis Multivariante , Hormona Paratiroidea/sangre , Fósforo/sangre , Prevalencia , Estudios Prospectivos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/etnología , Vitamina D/sangreRESUMEN
BACKGROUND: Progression of coronary artery calcium (CAC) is associated with increased risk of coronary heart disease (CHD) and is reported to be greater in whites than blacks, Hispanics, and Chinese in the US. Our objective was to compare progression of CAC between Japanese Americans and whites. METHODS: Population-based sample of 303 Japanese American men and 310 white men aged 40-49years, free of clinical cardiovascular disease at baseline, were examined for CAC at baseline (2004-2007) and follow-up (2008-2013). Progression of CAC was defined as change in coronary calcium scores (CCS) in participants with baseline CCS>0 and incident CAC in participants with baseline CCS=0. Multiple linear regression and relative risk regression were used to compare change in CCS scores and incident CAC between the two races, respectively. RESULTS: Japanese American men had significantly greater annual change in CCS than white men (median [interquartile range]: 11.3 Agatston units [1.4, 24.9] vs 2.5 [-0.22, 14.5]) in the unadjusted analyses. After adjusting for cardiovascular risk factors and follow-up time, change in CCS (beta±CI) and incidence rate ratio of CAC was similar in Japanese American men and white men: -0.12 (-0.34, 0.15) and (0.87 [95% CI: 0.20, 3.9]), respectively. CONCLUSIONS: In contrast to previously reported greater progression of CAC in whites than other races, we found a similar progression of CAC in Japanese American men as white men. Our study identifies Japanese American men as a target group for prevention of CHD. Large prospective studies are warranted to confirm these findings.
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Asiático , Calcinosis/etnología , Calcinosis/patología , Enfermedad de la Arteria Coronaria/etnología , Enfermedad de la Arteria Coronaria/patología , Población Blanca , Adulto , Estudios de Cohortes , Progresión de la Enfermedad , Hawaii , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pennsylvania , Factores de TiempoRESUMEN
To our knowledge, no study has investigated the association of long-term exposure to traffic pollution with markers of atherosclerosis in 4 vascular beds simultaneously in an all-African-American cohort. Among participants in the Jackson Heart Study (Jackson, Mississippi; baseline mean age = 55.5 (standard deviation, 12.7) years), we used linear regression to estimate percent differences in carotid intima-media thickness (CIMT) at baseline (2004) and used modified Poisson regression (robust error variance) to estimate prevalence ratios for peripheral artery disease (PAD), coronary artery calcification (CAC), and abdominal aortic calcification (AAC) at the first follow-up visit (2005-2008) for persons living less than 150 m (versus more than 300 m) from major roadways, adjusting for confounders. Living less than 150 m from such roadways was associated with a significant 6.67% (95% confidence interval: 1.28, 12.35) increase in CIMT (4,800 participants). PAD prevalence among persons living less than 150 m from a major roadway was 1.17 (95% confidence interval: 0.73, 1.86) times that of persons living more than 300 m away (4,443 participants), but this result was not statistically significant. There was no association for CAC or AAC. The association with CIMT was stronger in participants with a cardiovascular disease history than in those without one (P = 0.04). We observed an association in the carotid vascular beds but not the coronary, abdominal, or peripheral vascular beds. Our results highlight the need to consider residential proximity to roadways as a potential cardiovascular disease risk factor for blacks.
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Contaminantes Atmosféricos/efectos adversos , Aterosclerosis/etnología , Negro o Afroamericano , Grosor Intima-Media Carotídeo , Emisiones de Vehículos , Aorta Abdominal/patología , Enfermedades de la Aorta/etnología , Calcinosis/etnología , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/etnología , Humanos , Modelos Lineales , Persona de Mediana Edad , Mississippi/epidemiología , Enfermedad Arterial Periférica/etnología , Prevalencia , Medición de Riesgo , Factores de RiesgoRESUMEN
CONTEXT: Relative to European Americans, calcified atherosclerotic plaque (CP) is less prevalent and severe in African-Americans (AAs). OBJECTIVE: Predictors of progression of CP in the aorta, carotid, and coronary arteries were examined in AAs over a mean 5.3 ± 1.4-year interval. DESIGN: This is the African American-Diabetes Heart Study. SETTING: A type 2 diabetes (T2D)-affected cohort was included. PARTICIPANTS: A total of 300 unrelated AAs with T2D; 50% female, mean age 55 ± 9 years, baseline hemoglobin A1c 8.1 ± 1.8% was included. MAIN OUTCOME MEASURES: Glycemic control, renal parameters, vitamin D, and computed tomography-derived measures of adiposity, vascular CP, and volumetric bone mineral density (vBMD) in lumbar and thoracic vertebrae were obtained at baseline and follow-up. RESULTS: CP increased in incidence and quantity/mass in all three vascular beds over the 5-year study (P < .0001). Lower baseline lumbar and thoracic vBMD were associated with progression of abdominal aorta CP (P < .008), but not progression of carotid or coronary artery CP. Lower baseline estimated glomerular filtration rate was associated with progression of carotid artery CP (P = .0004), and higher baseline pericardial adipose volume was associated with progression of coronary artery (P = .001) and aorta (P = .0006) CP independent of body mass index. There was a trend for an inverse relationship between change in thoracic vBMD and change in aortic CP (P = .05). CONCLUSIONS: In this longitudinal study, lower baseline thoracic and lumbar vBMD and estimated glomerular filtration rate and higher pericardial adipose volumes were associated with increases in CP in AAs with T2D. Changes in these variables and baseline levels and/or changes in glycemic control, albuminuria, and vitamin D were not significantly associated with progression of CP.
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Tejido Adiposo/diagnóstico por imagen , Enfermedades de la Aorta/etnología , Aterosclerosis/etnología , Negro o Afroamericano/etnología , Densidad Ósea , Enfermedades de las Arterias Carótidas/etnología , Vasos Coronarios/diagnóstico por imagen , Diabetes Mellitus Tipo 2/etnología , Progresión de la Enfermedad , Placa Aterosclerótica/etnología , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/metabolismo , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/metabolismo , Calcinosis/diagnóstico por imagen , Calcinosis/etnología , Calcinosis/metabolismo , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/metabolismo , Comorbilidad , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/metabolismoRESUMEN
OBJECTIVES: Racial differences in susceptibility and progression of pancreatitis have been reported in epidemiologic studies using administrative or retrospective data. There has been little study, however, on the clinical profile, causes, and outcome of chronic pancreatitis (CP) in black patients. METHODS: We analyzed data on black patients with CP prospectively enrolled in the multicenter North American Pancreatitis Studies from 26 US centers during the years 2000-2014. CP was defined by definitive evidence on imaging studies or histology. Information on demographics, etiology, risk factors, disease phenotype, treatment, and perceived effectiveness was obtained from responses to detailed questionnaires completed by both patients and physicians. RESULTS: Of the 1,159 patients enrolled, 248 (21%) were black. When compared with whites, blacks were significantly more likely to be male (60.9 vs. 53%), ever (88.2 vs. 71.8%), or current smokers (64.2 vs. 45.9%), or have a physician-defined alcohol etiology (77 vs. 41.9%). There was no overall difference in the duration of CP although for alcoholic CP, blacks had a longer duration of disease (8.6 vs. 6.97 years; P=0.02). Blacks were also significantly more likely to have advanced changes on pancreatic morphology (calcifications (63.3 vs. 55.2%), atrophy (43.2 vs. 34.6%), pancreatic ductal stricture or dilatation (72.6 vs. 65.5%) or common bile duct stricture (18.6 vs. 8.2%)) and function (endocrine insufficiency 39.9 vs. 30.2%). Moreover, the prevalence of any (94.7 vs. 83%), constant (62.6 vs. 51%), and severe (78.4 vs. 65.8%) pain and disability (35.1 vs. 21.4%) were significantly higher in blacks. Observed differences were in part related to variances in etiology and duration of disease. No differences in medical or endoscopic treatments were seen between races although prior cholecystectomy (31.1 vs. 19%) was more common in white patients. CONCLUSIONS: Differences were observed between blacks and whites in the underlying cause, morphologic expression, and pain characteristics of CP, which in part are explained by the underlying risk factor(s) with alcohol and tobacco being much more frequent in black patients as well as disease duration.