RESUMO
OBJECTIVE: This study was to investigate the role of serum Klotho, fetuin-A, and Matrix Gla Protein (MGP) in Coronary Artery Calcification (CAC) in patients with Maintenance Hemodialysis (MHD) and their predictive value for CAC. METHODS: 100 patients receiving MHD were selected. Serum Klotho, fetuin-A, and MGP levels were detected by ELISA. CAC scores were assessed by coronary CT scan. Multifactor analysis was used to evaluate the risk factors affecting CAC. The ability of serum Klotho, fetuin-A, and MGP levels to diagnose CAC was evaluated by receiver operating characteristic curves. RESULTS: Serum Klotho, fetuin-A, and MGP were independent risk factors for CAC. Serum Klotho, fetuin-A, and MGP were valuable in the diagnosis of CAC in MHD patients. CONCLUSION: There is a close relationship between Klotho, fetuin-A, and MGP levels in MHD patients and CAC.
Assuntos
Biomarcadores , Proteínas de Ligação ao Cálcio , Doença da Artéria Coronariana , Proteínas da Matriz Extracelular , Glucuronidase , Proteínas Klotho , Proteína de Matriz Gla , Diálise Renal , Calcificação Vascular , alfa-2-Glicoproteína-HS , Humanos , Diálise Renal/efeitos adversos , Masculino , Feminino , Proteínas de Ligação ao Cálcio/sangue , Pessoa de Meia-Idade , alfa-2-Glicoproteína-HS/análise , alfa-2-Glicoproteína-HS/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Glucuronidase/sangue , Proteínas da Matriz Extracelular/sangue , Biomarcadores/sangue , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico por imagem , Idoso , Fatores de Risco , Ensaio de Imunoadsorção Enzimática , Adulto , Curva ROC , Calcinose/sangue , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Valor Preditivo dos TestesRESUMO
Valvular disease is a complex pathological condition that impacts countless individuals around the globe. Due to limited treatments, it is crucial to understand its mechanisms to identify new targets. Valve disease may result in pulmonary venous hypertension, which is linked to compromised functioning of the alveolar and capillary membranes and hindered gas exchange. Nonetheless, the correlation between surfactant proteins (SPs) and valve disease remains unexplored. A total of 44 patients were enrolled in this study, with 36 undergoing aortic valve replacement and 8 needing a second aortic valve substitution due to bioprosthetic valve degeneration. Ten healthy subjects were also included. The results showed that patients who underwent both the first valve replacement and the second surgery had significantly higher levels of immature SP-B (proSP-B) compared to control subjects. The levels of the extra-lung collectin SP-D were higher in patients who needed a second surgery due to bioprosthetic valve degeneration, while SP-A levels remained unchanged. The research also showed that there was no reciprocal relationship between inflammation and SP-D as the levels of inflammatory mediators did not differ between groups. The present study demonstrates that circulating proSP-B serves as a reliable marker of alveolar-capillary membrane damage in patients with valvular heart disease.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Calcinose , Proteína B Associada a Surfactante Pulmonar , Humanos , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/cirurgia , Masculino , Feminino , Proteína B Associada a Surfactante Pulmonar/sangue , Proteína B Associada a Surfactante Pulmonar/metabolismo , Idoso , Calcinose/sangue , Valva Aórtica/cirurgia , Valva Aórtica/patologia , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos de Casos e ControlesRESUMO
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.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Biomarcadores , Calcinose , LDL-Colesterol , Lipoproteína(a) , Índice de Gravidade de Doença , Humanos , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/diagnóstico por imagem , Feminino , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , LDL-Colesterol/sangue , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Calcinose/sangue , Calcinose/diagnóstico por imagem , Calcinose/diagnóstico , Calcinose/epidemiologia , Calcinose/etnologia , Idoso , Biomarcadores/sangue , Fatores de Risco , Medição de Risco , Incidência , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Valor Preditivo dos Testes , Fatores de Tempo , Estudos Prospectivos , Modelos de Riscos Proporcionais , Tomografia Computadorizada por Raios X , PrognósticoRESUMO
Background: Matrix metalloproteinase (MMP) enzyme gene polymorphisms MMP-2-1575G/A and MMP-9-1562C/T promoter polymorphism, their serum levels, and activity are associated with aortic valve calcification (AVC). Materials and Methods: The synergistic link between the risk of AVC and the alleles T and A of MMP-9 and MMP-2 was investigated, respectively. Ninety-two cases with AVC and 92 healthy individuals from the west of Iran were included, and MMP- 2-1575G/A and MMP-9-1562C/T promoter polymorphisms were detected using PCR-RFLP. The serum levels and activity of MMP-2 and -9 were assessed using ELISA and gelatin zymography methods, respectively. In addition, serum biochemical markers, including FBS, urea and creatinine, cholesterol, triglyceride, HDL, LDL, calcium, phosphorus, and blood pressure: systolic blood pressure and diastolic blood pressure were measured. Results: Heart valve calcification disease was associated with a comparatively higher frequency of the A allele of the MMP2-1575 variation (p = 0.002). In addition, the frequency of T allele of the MMP9-1562 variant was higher than the control group (p = 0.007). Conclusion: MMP-2 and MMP-9 serum levels and activities were observed to be considerably higher in the experimental group than in the control group (p < 0.001). Patients are more susceptible to cardiovascular disease than the control group due to elevated serum levels and activity of MMP-2 and MMP-9.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Calcinose , Predisposição Genética para Doença , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Regiões Promotoras Genéticas , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/sangue , Calcinose/genética , Calcinose/sangue , Feminino , Masculino , Irã (Geográfico) , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/sangue , Valva Aórtica/patologia , Regiões Promotoras Genéticas/genética , Pessoa de Meia-Idade , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/sangue , Polimorfismo de Nucleotídeo Único/genética , Idoso , Adulto , Alelos , Estudos de Casos e Controles , Frequência do Gene/genética , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/sangue , GenótipoRESUMO
Calcific aortic valve stenosis (CAVS) is characterized by increasing inflammation and progressive calcification in the aortic valve leaflets and is a major cause of death in the aging population. This study aimed to identify the inflammatory proteins involved in CAVS and provide potential therapeutic targets. We investigated the observational and causal associations of 92 inflammatory proteins, which were measured using affinity-based proteomic assays. Firstly, the case-control cohort identified differential proteins associated with the occurrence and progression of CAVS. Subsequently, we delved into exploring the causal impacts of these associated proteins through Mendelian randomization. This involved utilizing genetic instruments derived from cis-protein quantitative loci identified in genome-wide association studies, encompassing a cohort of over 400,000 individuals. Finally, we investigated the gene transcription and protein expression levels of inflammatory proteins by single-cell and immunohistochemistry analysis. Multivariate logistic regression and spearman's correlation analysis showed that five proteins showed a significant positive correlation with disease severity. Mendelian randomization showed that elevated levels of two proteins, namely, matrix metallopeptidase-1 (MMP1) and sirtuin 2 (SIRT2), were associated with an increased risk of CAVS. Immunohistochemistry and single-cell transcriptomes showed that expression levels of MMP1 and SIRT2 at the tissue and cell levels were significantly higher in calcified valves than in non-calcified control valves. These findings indicate that MMP1 and SIRT2 are causally related to CAVS and open up the possibility for identifying novel therapeutic targets.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Valva Aórtica/patologia , Biomarcadores , Calcinose , Mediadores da Inflamação , Metaloproteinase 1 da Matriz , Análise da Randomização Mendeliana , Proteômica , Humanos , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/genética , Calcinose/genética , Calcinose/metabolismo , Calcinose/sangue , Calcinose/patologia , Valva Aórtica/metabolismo , Masculino , Feminino , Idoso , Estudos de Casos e Controles , Biomarcadores/sangue , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/sangue , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Idoso de 80 Anos ou mais , Predisposição Genética para Doença , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/análise , FenótipoRESUMO
BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is not only a bone-derived factor involved in metabolism, but also a biomarker of kidney disease and cardiovascular pathophysiology. We conducted this cross-sectional observational study to explore relationships between plasma NGAL and thoracic aorta calcification (TAC) in maintenance hemodialysis (MHD) patients with and without diabetes. METHODS: Plasma NGAL was measured by ELISA, TAC was evaluated via computed tomography scan using a 3D quantification method or chest radiography aortic arch calcification score. Spearman correlation, Logistic regression and Partial correlation analysis were used to describe the correlations between NGAL and TAC. RESULTS: Plasma NGAL levels were lower in MHD patients with diabetes compared to those without diabetes (49.33(42.37, 55.48) vs 56.78(44.37, 674.13) ng/mL, P = 0.026). In MHD patients without diabetes, lg (NGAL) was positively correlated with ARC value(R = 0.612, P = 0.003) analyzed by Spearman correlation; for partial correlation analysis, lg (NGAL) was positively correlated with ARC value, after adjusting for age and sex (R = 0.550, P = 0.015), adjusting for age, sex and CHD (R = 0.565, P = 0.015), adjusting for age, sex, CHD and Alb (R = 0.536, P = 0.027), or adjusting for age, sex, CHD, Alb, and dialyzer membrane (polysulfone) (R = 0.590, P = 0.016); however, when adjusting for age, sex, CHD, Alb and Ca, the correlation between lg (NGAL) and ARC value disappeared. Positive correlation were found between NGAL and Ca (R = 0.644, P < 0.001), Ca and ACR (R = 0.534, P = 0.013) in Spearman coefficient analysis. CONCLUSION: There were positive correlations among plasma NGAL, serum Ca and ARC in MHD patients without diabetes; which suggests that NGAL is possibly a participant in cardiovascular calcification, in non-diabetic MHD.
Assuntos
Aorta Torácica , Doenças da Aorta , Calcinose , Falência Renal Crônica , Lipocalina-2 , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/sangue , Doenças da Aorta/complicações , Doenças da Aorta/patologia , Biomarcadores , Calcinose/sangue , Calcinose/complicações , Estudos Transversais , Complicações do Diabetes , Diabetes Mellitus , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Lipocalina-2/sangue , Diálise RenalRESUMO
BACKGROUND: Cardiac valve calcification (CVC) is an important risk factor for cardiovascular complications. However, limited data are available concerning the prevalence, clinical features and risk factors for CVC in end-stage kidney disease (ESKD) patients. In this study, we aimed to assess these parameters in Chinese ESKD patients receiving combination therapy with hemodialysis and hemodiafiltration. METHODS: We conducted a cross-sectional study on 293 ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration at the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. CVC was evaluated via echocardiography. RESULTS: ESKD patients with CVC had a higher prevalence of diabetes mellitus, aortic and/or coronary artery calcification, arrhythmia, heart failure and coronary heart disease; increased systolic, diastolic and pulse pressure; longer duration of hemodialysis and hypertension; reduced hemoglobin, albumin and high-density lipoprotein cholesterol levels; and increased serum calcium and calcium-phosphorus product levels compared with those without CVC. Logistic regression analysis showed that increased dialysis duration (p = 0.006, OR = 2.25), serum calcium levels (p = 0.046, OR = 2.04) and pulse pressure (p < 0.001, OR = 3.22), the presence of diabetes (p = 0.037, OR = 1.81) and decreased serum albumin levels (p = 0.047, OR = 0.54) were risk factors for CVC. The correlation analysis indicated a significantly increased CVCs prevalence with an increase prevalence of heart failure, aortic and coronary artery calcification. CONCLUSIONS: CVC represents a common complication and a danger signal for cardiovascular events in ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration. The presence of diabetes, increased pulse pressure, long dialysis duration, hypoalbuminemia and high serum calcium levels were independent risk factors for CVC.
Assuntos
Calcinose/sangue , Doenças das Valvas Cardíacas/sangue , Hemodiafiltração , Falência Renal Crônica/terapia , Idoso , Calcinose/etiologia , Cálcio/sangue , China , Estudos Transversais , Ecocardiografia , Feminino , Doenças das Valvas Cardíacas/etiologia , Humanos , Falência Renal Crônica/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: High plasma lipoprotein(a) and high body mass index are both causal risk factors for calcific aortic valve disease. OBJECTIVES: This study sought to test the hypothesis that risk of calcific aortic valve disease is the highest when both plasma lipoprotein(a) and body mass index are extremely high. METHODS: From the Copenhagen General Population Study, we used information on 69,988 randomly selected individuals recruited from 2003 to 2015 (median follow-up 7.4 years) to evaluate the association between high lipoprotein(a) and high body mass index with risk of calcific aortic valve disease. RESULTS: Compared with individuals in the 1st to 49th percentiles for both lipoprotein(a) and body mass index, the multivariable adjusted HRs for calcific aortic valve disease were 1.6 (95% CI: 1.3-1.9) for the 50th to 89th percentiles of both (16% of all individuals) and 3.5 (95% CI: 2.5-5.1) for the 90th to 100th percentiles of both (1.1%) (P for interaction = 0.92). The 10-year absolute risk of calcific aortic valve disease increased with higher lipoprotein(a), body mass index, and age, and was higher in men than in women. For women and men 70-79 years of age with body mass index ≥30.0 kg/m2, 10-year absolute risks were 5% and 8% for lipoprotein(a) ≤42 mg/dL (88 nmol/L), 7% and 11% for 42-79 mg/dL (89-169 nmol/L), and 9% and 14% for lipoprotein(a) ≥80 mg/dL (170 nmol/L), respectively. CONCLUSIONS: Extremely high lipoprotein(a) levels and extremely high body mass index together conferred a 3.5-fold risk of calcific aortic valve disease. Ten-year absolute risk of calcific aortic valve disease by categories of lipoprotein(a) levels, body mass index, age, and sex ranged from 0.4% to 14%.
Assuntos
Estenose da Valva Aórtica/sangue , Valva Aórtica/patologia , Índice de Massa Corporal , Calcinose/sangue , Previsões , Lipoproteína(a)/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/epidemiologia , Biomarcadores/sangue , Calcinose/diagnóstico , Calcinose/epidemiologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: Studies on cardiac structural and functional abnormalities in primary hyperparathyroidism (PHPT) have yielded conflicting and inconsistent results. In this prospective case-control study, we sought to compare cardiac structure and function in symptomatic PHPT patients and controls. METHODS: One hundred consecutive symptomatic PHPT patients and 113 matched controls underwent echocardiographic evaluation by the same operator. RESULTS: Left ventricular mass index (LVMI) was significantly higher in patients as compared to controls, (median of 90.95 g/m2 vs 86.5 g/m2, p = 0.041). Patients had significantly lower early trans-mitral diastolic flow (E velocity) as compared to controls (57.13 ± 14.88 vs 64.76 ± 15.45 cm/s, p < 0.001). Patients also had significantly lower early to late mitral annular velocity (E/A) as compared to controls (0.98 ± 0.37 vs 1.10 ± 0.34, p 0.013). Patients had higher frequency of aortic valve calcification (29% vs 2.65%, p < 0.001), mitral annular calcification (23% vs. 4.42%, p < 0.001), myocardial and septal calcifications (25% vs none, p < 0.001) as compared to controls. Serum PTH, calcium and uric acid significantly correlated with calcifications. Serum calcium showed a negative correlation with E/A ratio. CONCLUSIONS: Symptomatic patients with PHPT have substantial cardiac structural and functional abnormalities. These abnormalities include elevated LVMI, diastolic dysfunction, and aortic valve, mitral annular, septal and myocardial calcifications. We strongly suggest and conclude that the evaluation of PHPT patients should not only include traditional end organs like bones and kidneys but also the cardiovascular system in the form of echocardiography to detect subclinical cardiac dysfunction so that the cardiovascular health of such patients can be optimized.
Assuntos
Calcinose , Cardiomiopatias , Doenças das Valvas Cardíacas , Ventrículos do Coração , Hiperparatireoidismo Primário , Calcinose/sangue , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Cálcio/sangue , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Diagnóstico Precoce , Ecocardiografia/métodos , Ecocardiografia/estatística & dados numéricos , Feminino , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Hormônio Paratireóideo/sangueRESUMO
OBJECTIVE: The pathogenesis of calcinosis cutis, a disabling complication of SSc, is poorly understood and effective treatments are lacking. Inorganic pyrophosphate (PPi) is a key regulator of ectopic mineralization, and its deficiency has been implicated in ectopic mineralization disorders. We therefore sought to test the hypothesis that SSc may be associated with reduced circulating PPi, which might play a pathogenic role in calcinosis cutis. METHODS: Subjects with SSc and age-matched controls without SSc were recruited from the outpatient rheumatology clinics at Rutgers and Northwestern Universities (US cohort), and from the Universities of Szeged and Debrecen (Hungarian cohort). Calcinosis cutis was confirmed by direct palpation, by imaging or both. Plasma PPi levels were determined in platelet-free plasma using ATP sulfurylase to convert PPi into ATP in the presence of excess adenosine 5' phosphosulfate. RESULTS: Eighty-one patients with SSc (40 diffuse cutaneous, and 41 limited cutaneous SSc) in the US cohort and 45 patients with SSc (19 diffuse cutaneous and 26 limited cutaneous SSc) in the Hungarian cohort were enrolled. Calcinosis was frequently detected (40% of US and 46% of the Hungarian cohort). Plasma PPi levels were significantly reduced in both SSc cohorts with and without calcinosis (US: P = 0.003; Hungarian: P < 0.001). CONCLUSIONS: Circulating PPi are significantly reduced in SSc patients with or without calcinosis. Reduced PPi may be important in the pathophysiology of calcinosis and contribute to tissue damage with chronic SSc. Administering PPi may be a therapeutic strategy and larger clinical studies are planned to confirm our findings.
Assuntos
Calcinose/sangue , Calcinose/etiologia , Difosfatos/sangue , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Aterosclerose/diagnóstico por imagem , Aterosclerose/etnologia , Glicemia/metabolismo , Calcinose/diagnóstico por imagem , Calcinose/etnologia , Cartilagem Costal/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/sangue , Calcinose/sangue , Estudos de Coortes , Cartilagem Costal/metabolismo , Estudos Transversais , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
AIM: We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. MATERIAL AND METHODS: The study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2-3-4-5 chronic kidney disease (CKD) patients who did not require dialysis treatment. RESULTS: 32 (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD patients were included. The mean carotid intima-media thickness (CIMT), C-reactive protein (CRP), fetuin-A, OPG and MGP of the two groups were compared statistically. In CKD patients, age, body mass index (BMI), CRP, triglyceride, urea, systolic blood pressure (SBP), fasting blood sugar have a positive linear relationship, fetuin-A, OPG, GFR have a negative linear relationship with CIMT. The mean CIMT, right CIMT, left CIMT, blood urea, CRP, urinary albumin excretion creatinine and age show a negative linear relationship with fetuin-A. CONCLUSION: Fetuin-A levels begin to decline from the early stages of CKD and are significantly lower in patients with atherosclerosis as expressed with CIMT. This suggests that fetuin-A may be used as an early marker in CKD for increased cardiovascular risk. Early recognition of these risk factors is important and large-scale studies on vascular calcification inhibitors are needed.
Assuntos
Aterosclerose/sangue , Espessura Intima-Media Carotídea , Insuficiência Renal Crônica/sangue , alfa-2-Glicoproteína-HS/análise , Adulto , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Biomarcadores/sangue , Proteína C-Reativa/análise , Calcinose/sangue , Calcinose/complicações , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologiaRESUMO
ABSTRACT: Cystatin C is associated with atherosclerosis, but the relationship between cystatin C and coronary artery calcification (CAC) is uncertain. The purpose of this study was to evaluate the predictive value of cystatin C on the occurrence and severity of CAC.A total of 1447 hospitalized patients with coronary computed tomography angiography were selected in this study. According to the CAC score (CACS), patients were divided into calcification group (with CAC, nâ=â749) and control group (without CAC, nâ=â698). The calcification group was further divided into low calcification group (CACSâ<â100, nâ=â407), medium calcification group (CACS 100-400, nâ=â203), and high calcification group (CACS≥400, nâ=â139).Patients with CAC had higher cystatin C level than those in control group (Pâ<â.05). With the increase of calcification score, the cystatin C level showed an upward trend. The cystatin C level in the high calcification group was significantly higher than those in the low and medium calcification group (Pâ<â.05). ROC curve analysis showed that cystatin C had a high predictive value for the occurrence of CAC [area under the curve 0.640, 95% confidence interval (95% CI) 0.591-0.690, cut-off value 0.945âmg/L, sensitivity 0.683, specificity 0.558, Pâ<â.05] and severe CAC (area under the curve 0.638, 95% CI 0.550-0.762, cut-off value 0.965âmg/L, sensitivity 0.865, specificity 0.398, Pâ<â.05). Multivariate logistic regression analysis showed that cystatin C was an independent predictor of severe CAC (AOR 3.748, 95% CI 1.138-10.044, Pâ<â.05).Cystatin C was significantly associated with the occurrence and severity of CAC, suggesting that cystatin C had the potential as a predictor of CAC.
Assuntos
Calcinose/sangue , Doença da Artéria Coronariana/sangue , Cistatina C/sangue , Idoso , Calcinose/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC. METHODS: We included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC. RESULTS: The prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (ß 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase). CONCLUSIONS: Lp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Hiperlipoproteinemias , Reguladores do Metabolismo de Lipídeos/uso terapêutico , Lipoproteína(a) , Idoso , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/prevenção & controle , Calcinose/sangue , Calcinose/diagnóstico por imagem , Calcinose/epidemiologia , Calcinose/prevenção & controle , Estudos de Coortes , Correlação de Dados , Progressão da Doença , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/tratamento farmacológico , Hiperlipoproteinemias/epidemiologia , Lipoproteína(a)/sangue , Lipoproteína(a)/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Tomografia Computadorizada Multidetectores/estatística & dados numéricos , Países Baixos/epidemiologia , Prevalência , Tempo para o TratamentoRESUMO
BACKGROUND: The triglyceride glucose (TyG) index is a noninsulin-based marker for insulin resistance (IR) in general practice. Although smoking and heavy drinking have been regarded as major risk factors for various chronic diseases, there is limited evidence regarding the combined effects of smoking and alcohol consumption on IR. This study aimed to investigate the relationship between the TyG index and smoking and alcohol consumption using two Korean population-based datasets. METHODS: This study included 10,568 adults in the Korean National Health and Nutrition Examination Survey (KNHANES) and 9586 adults in the Korean Initiatives on Coronary Artery Calcification (KOICA) registry datasets. Multivariate logistic analysis was conducted to explore the relationship between smoking and alcohol consumption and the TyG index. To assess the predictive value of smoking and alcohol consumption on high TyG index, the area under the curve (AUC) were compared and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were derived. RESULTS: The combined effect of smoking and alcohol consumption was an independent risk factor of a higher TyG index in the KNHANES (adjusted odds ratio: 4.33, P < .001) and KOICA (adjusted odds ratio: 1.94, P < .001) datasets. Adding smoking and alcohol consumption to the multivariate logistic models improved the model performance for the TyG index in the KNHANES (AUC: from 0.817 to 0.829, P < .001; NRI: 0.040, P < .001; IDI: 0.017, P < .001) and KOICA (AUC: from 0.822 to 0.826, P < .001; NRI: 0.025, P = .006; IDI: 0.005, P < .001) datasets. CONCLUSIONS: Smoking and alcohol consumption were independently associated with the TyG index. Concurrent smokers and alcohol consumers were more likely to have a TyG index that was ≥8.8 and higher than the TyG indices of non-users and those who exclusively consumed alcohol or smoking tobacco.
Assuntos
Consumo de Bebidas Alcoólicas/sangue , Glicemia/metabolismo , Calcinose/sangue , Doença da Artéria Coronariana/sangue , Fumar/sangue , Triglicerídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Área Sob a Curva , Calcinose/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Conjuntos de Dados como Assunto , Humanos , Resistência à Insulina , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Sistema de Registros , República da Coreia/epidemiologia , Fatores de Risco , Fumar/epidemiologiaAssuntos
Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Hiperlipoproteinemias , Reguladores do Metabolismo de Lipídeos/uso terapêutico , Lipoproteína(a) , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/prevenção & controle , Calcinose/sangue , Calcinose/diagnóstico , Calcinose/prevenção & controle , Progressão da Doença , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/tratamento farmacológico , Lipoproteína(a)/sangue , Lipoproteína(a)/metabolismo , Seleção de Pacientes , Prevenção Secundária/ética , Prevenção Secundária/métodos , Tempo para o TratamentoRESUMO
BACKGROUND: In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges. METHODS: We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment. RESULTS: The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1; P=0.006). This effect was pronounced in older (aged 65-74 years) versus younger (aged 20-64 years) participants (P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores. CONCLUSIONS: Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048.
Assuntos
Calcinose/sangue , Calcinose/etiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/etiologia , Fosfatos/sangue , Diálise Renal/efeitos adversos , Adulto , Idoso , Calcinose/prevenção & controle , Doença da Artéria Coronariana/prevenção & controle , Progressão da Doença , Combinação de Medicamentos , Feminino , Compostos Férricos/efeitos adversos , Compostos Férricos/uso terapêutico , Humanos , Hiperfosfatemia/complicações , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/prevenção & controle , Lantânio/efeitos adversos , Lantânio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Sequestrantes/efeitos adversos , Sequestrantes/uso terapêutico , Sacarose/efeitos adversos , Sacarose/uso terapêutico , Adulto JovemRESUMO
In calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the effect of menaquinone 4 (MK4/vitamin K2) on valvular calcification in the hypercholesterolemic mouse model of CAVD. LDLr-/-ApoB100/100 male mice were fed with a Western diet for 5 months, with (n = 10) or without (n = 10) added 0.2 mg/g MK4. Body weight gain was followed weekly. Morphology of aortic valves and liver was assessed with immunohistochemistry. Plasma cholesterol levels and cytokines from hepatic tissue were assessed in the end of the study. Hepatic gene expression of lipid metabolism regulating genes were assessed after 18 h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemic LDLr-/- ApoB100/100 mice. The MK4-containing WD diet increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of genes required for triglyceride and cholesterol synthesis. MK4 diminished levels of several cytokines and chemokines in liver, including IL-6, TNFα and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.
Assuntos
Estenose da Valva Aórtica/tratamento farmacológico , Valva Aórtica/patologia , Apolipoproteínas B/genética , Calcinose/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Receptores de LDL/genética , Vitamina K 2/farmacologia , Animais , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/patologia , Calcinose/sangue , Calcinose/genética , Calcinose/patologia , Modelos Animais de Doenças , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Lipídeos/sangue , Lipoproteínas LDL/sangue , Camundongos , Camundongos Knockout , Fatores de Risco , Triglicerídeos/sangueRESUMO
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.
Assuntos
Aorta Torácica , Doenças da Aorta/sangue , Calcinose/sangue , Doença da Artéria Coronariana/sangue , Doenças das Valvas Cardíacas/sangue , Lipoproteína(a)/sangue , Valva Mitral , Calcificação Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/etnologia , Biomarcadores/sangue , Calcinose/diagnóstico por imagem , Calcinose/etnologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etnologia , Estudos Transversais , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/etnologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Prevalência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etnologiaRESUMO
BACKGROUND: Studies evaluating endocrine and exocrine functions in fibrocalculous pancreatic diabetes (FCPD) are scarce. METHODS: Insulin, C-peptide, glucagon, incretin hormones (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide [GIP]), and dipeptidyl peptidase IV (DPP-IV) were estimated in patients with FCPD (n = 20), type 2 diabetes mellitus (T2DM) (n = 20), and controls (n = 20) in fasting and 60 minutes after 75 g glucose. RESULTS: Fasting and post-glucose C-peptide and insulin in FCPD were lower than that of T2DM and controls. Plasma glucagon decreased after glucose load in controls (3.72, 2.29), but increased in T2DM (4.01, 5.73), and remained unchanged in FCPD (3.44, 3.44). Active GLP-1 (pmol/L) after glucose load increased in FCPD (6.14 to 9.72, P = <.001), in T2DM (2.87 to 4.62, P < .001), and in controls (3.91 to 6.13, P < .001). Median active GLP-1 in FCPD, both in fasting and post-glucose state (6.14, 9.72), was twice that of T2DM (2.87, 4.62) and 1.5 times that of controls (3.91, 6.13) (P < .001 for all). Post-glucose GIP (pmol/L) increased in all: FCPD (15.83 to 94.14), T2DM (21.85 to 88.29), and control (13.00 to 74.65) (P < .001 for all). GIP was not different between groups. DPP-IV concentration (ng/mL) increased in controls (1578.54, 3012.00) and FCPD (1609.95, 1995.42), but not in T2DM (1204.50, 1939.50) (P = .131). DPP-IV between the three groups was not different. Fecal elastase was low in FCPD compared with T2DM controls. CONCLUSIONS: In FCPD, basal C-peptide and glucagon are low, and glucagon does not increase after glucose load. GLP-1, but not GIP, in FCPD increases 1.5 to 2 times as compared with T2DM and controls (fasting and post glucose) without differences in DPP-IV.