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1.
Artigo em Inglês | MEDLINE | ID: mdl-32020410

RESUMO

Previous studies demonstrated that men were more likely to have plaque rupture and are at greater risk for myocardial infarction and stroke than women. We evaluated differences in carotid plaque characteristics by MRI between men and women with mild-moderate atherosclerosis and elevated ApoB levels. One hundred eighty-two subjects (104 men and 78 women) with CAD or carotid stenosis (≥ 15% by ultrasound), ApoB ≥ 120 mg/dL and carotid MRI scan were included. Percent wall volume (%WV) was calculated as (wall volume/total vessel volume) × 100%. Three major plaque compositions, fibrous tissue (FT), calcification (CA) and lipid rich necrotic core (LRNC), were identified and quantified using published MRI criteria. Adventitial and plaque neovascularization as fractional plasma volume (Vp) and permeability as transfer constant (Ktrans) were analyzed using kinetic modeling. These characteristics were compared between men and women. Men, compared to women, were younger (54 ± 8 vs. 58 ± 8 years, p = 0.01), had higher rate of previous MI (46 vs. 26%, p = 0.005) but lower proportions of metabolic syndrome (37 vs. 59%, p = 0.003). After adjusting for between-gender differences, men were significantly more likely to have LRNC (OR 2.22, 95% CI 1.04-4.89, p = 0.04) and showed significantly larger %LRNC than women (diff = 4.3%, 95% CI 1.6-6.9%, p = 0.002), while %WV, FT, and CA were similar between men and women. There were no statistically significant differences in adventitial and plaque Vp or Ktrans. Men were significantly more likely to have LRNC and had larger LRNC than women. However, men and women showed relatively similar levels of adventitial and plaque neovascularization and permeability.Trial registration: NCT00715273 at ClinicalTrials.gov. Registered 15 July 2008, retrospectively registered.

2.
Coron Artery Dis ; 31(2): 109-117, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31464730

RESUMO

BACKGROUND: This study investigated whether the age, creatinine, and ejection fraction (ACEF) score [age (years) /ejection fraction (%) +1 (if creatinine>176µmol/L)] could predict 1-year outcomes following ST-segment elevation myocardial infarction after percutaneous coronary intervention, and whether accuracy could be improved by establishing novel ACEF-derived risk models. METHODS: A total of 1146 patients were included. The study endpoint was 1-year major adverse cardio-cerebrovascular events, including all-cause death, nonfatal myocardial infarction, unplanned revascularization, and nonfatal stroke. Accuracy was defined with area under the curve by receiver-operating characteristic curve analysis. RESULTS: The incidence of 1-year major adverse cardio-cerebrovascular event increased with the rising age, creatinine, and ejection fraction score tertiles (4.8%, 8.4%, and 15.2%, P < 0.001 for all). Higher ACEF score was significantly associated with an increased risk of the endpoint in overall (odds ratio = 3.75, 95% confidence interval, 2.44-5.77, P < 0.001) and in subgroups (all P < 0.05). The accuracy of the ACEF score was equivalent to the other complex risk scores. The combination of ACEF, and diabetes (ACEF-diabetes score) yielded a superior discriminatory ability than the original ACEF score (increase in C-statistic from 0.67 to 0.71, P = 0.048; continuous net reclassification improvement = 51.9%, 95% confidence interval, 33.4-70.5%, P < 0.001; integrated discrimination improvement = 0.020, 95% confidence interval, 0.011-0.030, P < 0.001). CONCLUSIONS: The simplified ACEF score performed well in predicting 1-year outcomes in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention. The novel ACEF-diabetes score provided a better predictive value and thus may help stratify high-risk patients and potentially facilitate decision making.

3.
Angiology ; 71(1): 38-47, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31554413

RESUMO

This study investigated whether a novel index of stress hyperglycemia might have a better prognostic value compared to admission glycemia alone in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The acute-to-chronic glycemic ratio was expressed as admission blood glucose (ABG) devided by the estimated average glucose (eAG), and eAG was derived from the glycated hemoglobin (HbA1c). A total of 1300 consecutive patients with STEMI treated with PCI were included. Baseline data and outcomes were analyzed. The study end point was a composite of in-hospital all-cause death, cardiogenic shock, and acute pulmonary edema. Accuracy was defined with area under the curve (AUC) by a receiver-operating characteristic (ROC) curve analysis. After multivariate adjustment, both ABG/eAG and ABG were closely associated with an increased risk of the composite end point in nondiabetic patients. However, only ABG/eAG (odds ratio = 2.45, 95% confidence interval: 1.24-4.82, P = .010), instead of ABG, was associated with the outcomes in diabetic patients. Compared to ABG, ABG/eAG had an equivalent predictive value in nondiabetic patients but a superior discriminatory ability in diabetic patients (AUC improved from 0.52-0.63, P < .001). Taken together, ABG/eAG provides more significant in-hospital prognostic information than ABG in diabetic patients with STEMI after PCI.


Assuntos
Glicemia/metabolismo , Hemoglobina A Glicada/metabolismo , Admissão do Paciente , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Fatores de Tempo , Resultado do Tratamento
4.
J Clin Lipidol ; 13(5): 847-853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31783975

RESUMO

BACKGROUND: Statin therapy can improve plaque stability. However, the time course of effects of statin on adventitial angiogenesis and plaque neovascularization has not been studied. OBJECTIVE: The objective of the study was to investigate whether statin therapy reduces plaque neovascularization, associated with adventitial angiogenesis, over 24 months as assessed by using carotid dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: Forty-three lipid treatment-naïve subjects with asymptomatic carotid atherosclerosis received rosuvastatin (5-20 mg/d) to lower low-density lipoprotein cholesterol to <80 mg/dL for 24 months. Carotid DCE-MRI was performed at baseline, 3, 12 and 24 months. Vascularity (Vp = fractional plasma volume) and vascular permeability (Ktrans = transfer constant) derived from kinetic modeling of DCE-MRI were measured in both adventitia and plaque. RESULTS: Adventitia Vp and adventitia Ktrans were significantly correlated with plaque Vp and plaque Ktrans at baseline. Rosuvastatin significantly reduced both adventitial and plaque Vp significantly at 3 months from 0.121 ± 0.064 to 0.085 ± 0.049 (P = .008) and from 0.096 ± 0.052 to 0.067 ± 0.043 (P = .013). Adventitial and plaque Vp continued to decrease by 43% and 34% at 12 months and by 49% and 45% at 24 months. However, the continued reductions from 3 to 12 months and from 12 to 24 months were not statistically significant. Adventitial and plaque Ktrans showed similar trends, but nonstatistically significant decreases during the 24 months of treatment. CONCLUSIONS: Rosuvastatin therapy rapidly and significantly decreased adventitial and plaque neovascularization at 3 months followed by continued, but nonstatistically significant, decreases at 12 and 24 months.

5.
Biomed Pharmacother ; 120: 109527, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629953

RESUMO

Excessive formation of advanced glycation end products (AGEs) impairs voltage-gated potassium (Kv) channels in rat coronary artery smooth muscle cells (CSMCs), resulting in weakened Kv-mediated coronary vasodilation. We hypothesized that induction of the nuclear factor-κB (NF-κB) signaling pathway by AGEs plays a significant role in the regulation of Kv channel-mediated vasodilation in Zucker diabetic fatty (ZDF) rats. Assays of mRNA transcripts, protein expression, and intracellular localization as well as patch-clamp experiments in cultured CSMCs revealed that AGEs significantly induced activation of the NF-κB signaling pathway, reduced Kv1.2/1.5 expression, and inhibited Kv currents. In addition, silencing of the receptor for AGEs (RAGE) or p65 with siRNA and treatment with alagrebrium (ALA) or pyrrolidine dithiocarbamate (PDTC) alleviated the AGE-induced impairment of Kv channels in CSMCs. Compared with Zucker lean (ZL) rats, the amount of AGEs, RAGE protein expression, and NF-κB activity in coronary arteries were higher in ZDF rats; whereas Kv1.2/1.5 expression was significantly lower in ZDF rats. Reduced Kv1.2/1.5 expression in coronary arteries and impaired Kv-mediated coronary relaxation tested by wire myography in ZDF rats were markedly improved by treatment with aminoguanidine (AG), ALA, or PDTC. These effects were accompanied by diminished NF-κB activity, inflammation, and oxidative stress. Taken together, these results indicate that an increased interaction between AGEs and RAGE in diabetic rats leads to impaired Kv channel-mediated coronary vasodilation. Moreover, activation of the NF-κB signaling pathway and a subsequent increase of inflammation and oxidative stress may play an important role in AGE-induced impairment of coronary vasodilation in diabetes.

6.
Am J Cardiol ; 124(4): 476-484, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31235063

RESUMO

The prognostic value of the CHA2DS2-VASc score in acute coronary syndrome (ACS) patients without atrial fibrillation (AF) who underwent percutaneous coronary intervention remains uncertain. We examine the association of the CHA2DS2-VASc score and major adverse cardiovascular events (MACE) in this population and compared its risk prediction with 2 other commonly used risk scores (Global Registry of Acute Coronary Events [GRACE] and thrombolysis in myocardial infarction [TIMI]). A total of 3,745 consecutive ACS patients without AF who underwent percutaneous coronary intervention during 2013 to 2017 were classified into 4 groups according to the CHA2DS2-VASc score: low (0 to 1), moderate (2 to 3), high (4 to 5), and very high (>5). Incidences of MACE including cardiovascular death, nonfatal myocardial infarction, or stroke in-hospital and during a median follow-up of 33 months were compared among the 4 groups. Receiver-operating characteristic curves were generated to compare CHA2DS2-VASc with GRACE and TIMI for risk prediction. The incidences of in-hospital MACE (3.5%, 6.6%, 7.6%, and 9.1%, p <0.001) and mid-term follow-up MACE (4.5%, 7.1%, 13.1%, and 16.1%, p <0.001) were significantly higher as the CHA2DS2-VASc score increased. The CHA2DS2-VASc score was an independent predictor of subsequent MACE (hazard ratio = 1.31, 95% CI 1.24 to 1.39, p <0.001), and the very high-risk score group showed 3.8-fold increased risk of MACE than the low-risk score group. Receiver-operating characteristic curves showed that the CHA2DS2-VASc score was comparable to the GRACE score and to TIMI-STEMI, but, better than the TIMI-NSTEMI/unstable angina pectoris score in terms of predicting MACE. In conclusion, higher CHA2DS2-VASc score was independently associated with increased risk of MACE in the ACS patients without AF who underwent PCI.

7.
J Am Heart Assoc ; 7(19): e009162, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30371311

RESUMO

Background Cardiorenal syndrome type 1 ( CRS 1) as a complication of acute myocardial infarction can lead to adverse outcomes, and a method for early detection is needed. This study investigated the individual and integrated effectiveness of amino-terminal pro-brain natriuretic peptide (Pro-BNP), estimated glomerular filtration rate (eGFR), and high-sensitivity C-reactive protein (CRP) as predictive factors for CRS 1 in patients with acute myocardial infarction. Methods and Results In a retrospective analysis of 2094 patients with acute myocardial infarction, risk factors for CRS 1 were analyzed by logistic regression. Receiver operating characteristic curves were constructed to determine the predictive ability of the biomarkers individually and in combination. Overall, 177 patients (8.45%) developed CRS 1 during hospitalization. On multivariable analysis, all 3 biomarkers were independent predictors of CRS 1 with odds radios and 95% confidence intervals for a 1-SD change of 1.792 (1.311-2.450) for log(amino-terminal pro-brain natriuretic peptide, 0.424 (0.310-0.576) for estimated glomerular filtration rate, and 1.429 (1.180-1.747) for high-sensitivity C-reactive peptide. After propensity score matching, the biomarkers individually and together significantly predicted CRS 1 with areas under the curve of 0.719 for amino-terminal pro-brain natriuretic peptide, 0.843 for estimated glomerular filtration rate, 0.656 for high-sensitivity C-reactive peptide, and 0.863 for the 3-marker panel (all P<0.001). Also, the integrated 3-marker panel performed better than the individual markers ( P<0.05). CRS 1 risk correlated with the number of biomarkers showing abnormal levels. Abnormal measurements for at least 2 biomarkers indicated a greater risk of CRS 1 (odds ratio 36.19, 95% confidence interval 8.534-153.455, P<0.001). Conclusions The combination of amino-terminal pro-brain natriuretic peptide, estimated glomerular filtration rate, and high-sensitivity C-reactive peptide at presentation may assist in the prediction of CRS 1 and corresponding risk stratification in patients with acute myocardial infarction.


Assuntos
Proteína C-Reativa/metabolismo , Síndrome Cardiorrenal/sangue , Taxa de Filtração Glomerular/fisiologia , Infarto do Miocárdio/complicações , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Síndrome Cardiorrenal/etiologia , Síndrome Cardiorrenal/fisiopatologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Valor Preditivo dos Testes , Prognóstico , Precursores de Proteínas , Estudos Retrospectivos , Taxa de Sobrevida/tendências
8.
J Cardiol ; 72(3): 215-219, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29580665

RESUMO

BACKGROUND: Low triiodothyronine (T3) syndrome (LT3S) is frequently seen in patients with acute myocardial infarction (AMI). We examined the association between LT3S and severity of myocardial injury and determined whether LT3S adds predictive value over thrombolysis in myocardial infarction (TIMI) risk score for in-hospital cardiovascular (CV) death. METHODS: Of 2459 AMI patients, 529 pairs of euthyroid and LT3S individuals with similar baseline characteristics were identified using 1:1 propensity score matching. LT3S was defined as free T3 (fT3) <2.36pg/mL, normal values of thyroid-stimulating hormone and free thyroxin. Primary outcome was in-hospital CV death. Receiver operating characteristic curves were generated to assess the predictive effects of fT3, TIMI risk score, and TIMI-LT3S risk score on in-hospital CV death. RESULTS: LT3S was found in 23.3% of patients with AMI. The peak values of cardiac troponin I in ng/mL and N-terminal pro-brain natriuretic peptide in ng/mL were significantly higher in LT3S: 6.6 (1.3-19.6) vs. 3.5 (0.8-12.1), p<0.001 and 3625 (1046-12,776) vs. 2158 (774-6759), p<0.001. Patients with LT3S had significantly higher rate of in-hospital CV death than those without (4.7% vs. 1.7%, p=0.005). Lower levels of fT3 yielded an area under the curve (AUC) of 0.741 for predicting CV death. LT3S, when added to the TIMI risk score, significantly increased AUC for in-hospital CV death than TIMI risk score alone (0.775 vs. 0.738, p=0.005). CONCLUSIONS: LT3S was associated with more severe myocardial injury and increased in-hospital CV mortality in patients with AMI. Furthermore, it improved risk prediction of in-hospital CV death post-AMI when it was added to the TIMI risk score.


Assuntos
Síndromes do Eutireóideo Doente/mortalidade , Mortalidade Hospitalar , Infarto do Miocárdio/mortalidade , Índice de Gravidade de Doença , Tri-Iodotironina/sangue , Idoso , Área Sob a Curva , Causas de Morte , Síndromes do Eutireóideo Doente/sangue , Síndromes do Eutireóideo Doente/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Valor Preditivo dos Testes , Pontuação de Propensão , Curva ROC , Medição de Risco
9.
Arterioscler Thromb Vasc Biol ; 38(3): 673-678, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29301785

RESUMO

OBJECTIVE: To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)-lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes). APPROACH AND RESULTS: AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging. Plaque burden was measured by the percent wall volume (%WV) of the carotid artery. Associations between annualized change in %WV with baseline and on-study (1 year) lipid variables were evaluated using multivariate linear regression and the Bonferroni correction to account for multiple comparisons. Average %WV at baseline was 41.6±6.8% and annualized change in %WV over 2 years ranged from -3.2% to 3.7% per year (mean: 0.2±1.1% per year; P=0.032). Increases in %WV were significantly associated with higher baseline Lp(a) (ß=0.34 per 1-SD increase of Lp(a); 95% confidence interval, 0.15-0.52; P<0.001) after adjusting for clinical risk factors and other lipid levels. On-study Lp(a) had a similar positive association with %WV progression (ß=0.33; 95% confidence interval, 0.15-0.52; P<0.001). CONCLUSIONS: Despite intensive lipid therapy, aimed at aggressively lowering LDL-C to <70 mg/dL, carotid atherosclerosis continued to progress as assessed by carotid magnetic resonance imaging and that elevated Lp(a) levels were independent predictors of increases in atherosclerosis burden.


Assuntos
Artérias Carótidas/efeitos dos fármacos , Doenças das Artérias Carótidas/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipoproteína(a)/sangue , Angiografia por Ressonância Magnética , Placa Aterosclerótica , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
J Clin Lipidol ; 11(6): 1309-1317, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28927896

RESUMO

Niacin (nicotinic acid) has been used for primary and secondary coronary heart disease prevention for over 40 years. Until recently clinical trials incorporating niacin as part of an intervention strategy consistently demonstrated reduction in clinical events and lesion improvement, including ≥6% absolute mortality reduction. Two large clinical event trials in 2011 (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) and 2014 (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) concluded that niacin added to statin therapy did not provide clinical event benefit over statin alone. This has prompted some individuals to call for an end to the use of niacin in statin-treated patients and the US Food and Drug Administration to halt marketing of statin/niacin combination tablets. There are significant differences between the earlier clinical trials that revealed cardiovascular benefit of niacin and the 2 trials that failed to demonstrate a benefit. These differences include dyslipidemia types, niacin formulation, dosing, and timing. In general, the patient population that benefits the most from incorporating niacin in their treatment regimen can be defined by elevations in low-density lipoprotein cholesterol and triglycerides, and reduced high-density lipoprotein cholesterol. The niacin formulation and dose should be capable of achieving adequate lipoprotein change. Mealtime dosing of niacin, as opposed to bedtime dosing, may avoid a counter-regulatory hormone response, including catecholamines, because of altered fuel supply potentially leading to unexpected cardiovascular outcomes.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Niacina/uso terapêutico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , HDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Dislipidemias/sangue , Dislipidemias/patologia , Humanos , Triglicerídeos/sangue
12.
J Clin Lipidol ; 11(2): 362-368, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28502492

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) has reported to be a major public health crisis in China. OBJECTIVE: We examined the incidence of new T2DM over 4 years for association of clinical factors and lipids with development of T2DM in a community-based population. METHODS: We included 923 Chinese subjects who participated in community-organized health checkout in both 2009 and 2013. Health history was collected; physical examination was performed; biochemistry, lipids, and glucose were measured. Of 923, 819 were confirmed without T2DM in 2009 and included in the analysis. Unadjusted and adjusted logistic regression models were used to estimate the effects of clinical factors and biomarkers on the risk of new T2DM. RESULTS: Of 819 subjects without T2DM in 2009, 65 were identified as T2DM in 2013, 8% over 4 years. These 65 subjects, compared with those 754 without new T2DM, were older, more likely to be male and smokers. They had higher body mass index (BMI), fasting glucose, blood pressure and triglycerides, and lower levels of high-density lipoprotein-cholesterol and apolipoprotein A1 (ApoA1). Multivariate logistic regression identified larger BMI (odds ratio [OR] = 1.7; 95% confidence interval [CI], 1.22-2.39, P = .002), higher fasting glucose levels (OR = 4.2, 95% CI, 2.90-6.19, P < .001), and low levels of ApoA1 (OR = 0.51, 95% CI 0.33-0.76, P = .002) were independently associated with new T2DM. Furthermore, receiver operating characteristics curves for multivariate models for new T2DM showed that area under the curve improved from 0.87 to 0.89 when adding ApoA1 to the Framingham Diabetes Risk Scoring Model and from 0.85 to 0.89 when adding ApoA1 to a 4-variable (age, BMI, glucose, and triglycerides) Chinese model. CONCLUSIONS: There is a high incidence of new T2DM at 8% over 4 years among Chinese. Larger BMI, higher glucose levels, and lower levels of ApoA1 are significantly and independently associated with new T2DM. Lower ApoA1 improves the risk prediction of new type 2 diabetes when it was added to the existing risk models.


Assuntos
Apolipoproteína A-I/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Medição de Risco
13.
Cardiovasc Diabetol ; 16(1): 45, 2017 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-28381225

RESUMO

BACKGROUND: The risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors. METHODS: PAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events. RESULTS: ACS patients with T2DM had higher PAPP-A (19.29 ± 16.36 vs. 13.29 ± 13.90 ng/ml, p < 0.001) and higher rate of CV events 2 years post ACS (27.2 vs. 13.6%, p = 0.002) than those without. Higher levels of PAPP-A were significantly associated with increased risk of CV events during 2-year follow-up [HR = 2.97 for 1 SD increase in log10(PAPP-A), 95% CI 2.11-4.18, p < 0.001] in T2DM and (HR = 3.16, 95% CI 2.27-4.39, p < 0.001) in non-T2DM. Among patients with T2DM, PAPP-A showed a larger area under the curve (AUC 0.79) that was significantly more predictive than hsCRP (AUC 0.64), eGFR (AUC 0.66) and LVEF < 50% (AUC 0.52); predictive ability did not improve significantly by including those factors into the model. CONCLUSIONS: Patients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM. Trial registration ISRCTN10805074. Registered on 20 January 2017, retrospectively registered.


Assuntos
Síndrome Coronariana Aguda/sangue , Diabetes Mellitus Tipo 2/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/etiologia , Proteína Plasmática A Associada à Gravidez/análise , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Admissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Recidiva , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Fatores de Tempo , Regulação para Cima
14.
JACC Cardiovasc Imaging ; 10(3): 241-249, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28279371

RESUMO

OBJECTIVES: The aim of this study was to investigate whether and what carotid plaque characteristics predict systemic cardiovascular outcomes in patients with clinically established atherosclerotic disease. BACKGROUND: Advancements in atherosclerosis imaging have allowed assessment of various plaque characteristics, some of which are more directly linked to the pathogenesis of acute cardiovascular events compared to plaque burden. METHODS: As part of the event-driven clinical trial AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes), subjects with clinically established atherosclerotic disease underwent multicontrast carotid magnetic resonance imaging (MRI) to detect plaque tissue composition and high-risk features. Prospective associations between MRI measurements and the AIM-HIGH primary endpoint (fatal and nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, and symptom-driven revascularization) were analyzed using Cox proportional hazards survival models. RESULTS: Of the 232 subjects recruited, 214 (92.2%) with diagnostic image quality constituted the study population (82% male, mean age 61 ± 9 years, 94% statin use). During median follow-up of 35.1 months, 18 subjects (8.4%) reached the AIM-HIGH endpoint. High lipid content (hazard ratio [HR] per 1 SD increase in percent lipid core volume: 1.57; p = 0.002) and thin/ruptured fibrous cap (HR: 4.31; p = 0.003) in carotid plaques were strongly associated with the AIM-HIGH endpoint. Intraplaque hemorrhage had a low prevalence (8%) and was marginally associated with the AIM-HIGH endpoint (HR: 3.00; p = 0.053). High calcification content (HR per 1 SD increase in percent calcification volume: 0.66; p = 0.20), plaque burden metrics, and clinical risk factors were not significantly associated with the AIM-HIGH endpoint. The associations between carotid plaque characteristics and the AIM-HIGH endpoint changed little after adjusting for clinical risk factors, plaque burden, or AIM-HIGH randomized treatment assignment. CONCLUSIONS: Among patients with clinically established atherosclerotic disease, carotid plaque lipid content and fibrous cap status were strongly associated with systemic cardiovascular outcomes. Markers of carotid plaque vulnerability may serve as novel surrogate markers for systemic atherothrombotic risk.


Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Imagem por Ressonância Magnética , Placa Aterosclerótica , Síndrome Coronariana Aguda/etiologia , Idoso , Isquemia Encefálica/etiologia , Canadá , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/terapia , Artéria Carótida Primitiva/química , Artéria Carótida Primitiva/patologia , Intervalo Livre de Doença , Feminino , Fibrose , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Ruptura Espontânea , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Estados Unidos
16.
J Clin Lipidol ; 10(5): 1091-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27678425

RESUMO

BACKGROUND: Cardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia. OBJECTIVES: The clinical benefit of intensive lipid therapy over 25 years was investigated in the Familial Atherosclerosis Treatment Study-Observational Study. METHODS: Of 175 coronary artery disease subjects with mean low-density lipoprotein cholesterol (LDL-C) of 191 mg/dL and mean age of 50 years, who completed the randomized and placebo-controlled Familial Atherosclerosis Treatment Study, 100 chose receiving lipid management by their physicians (usual care [UC]) and 75 elected to receive an intensive treatment [IT] for lipid management with lovastatin (40 mg/d), niacin (2.5 g/d), and colestipol (20 g/d) from 1989 to 2004, followed by double therapy with simvastatin (40-80 mg/d) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40 to 80 mg/d plus niacin during 2007 to 2012. Deaths from CVD, non-CVD, and any cause were compared between UC and IT using Cox proportional hazards model. RESULTS: UC and IT groups were similar in risk factors with the exception that IT had more severe coronary artery disease. Mean LDL-C levels were 167 mg/dL from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119, 97, and 83 mg/dL in the 3 periods, respectively. Compared with UC, IT significantly reduced total mortality (11.1 vs 26.3 per 1000 person years [PY], hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.26-0.77, P = .003) and CVD mortality (10.6 vs 27.7 per 1000 PY, HR = 0.34, 95% CI: 0.15-0.80, P = .009). The non-CVD mortality was also reduced but was not of statistical significance (6.8 vs 12.7 per 1000 PY, HR = 0.55, 95% CI: 0.27-1.14, P = .11). CONCLUSIONS: Long-term intensive lipid therapy significantly reduced total and cardiovascular mortality in Familial Atherosclerosis Treatment Study-Observational Study. These results support the importance of lifetime risk management to improve long-term outcome.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Adulto , Aterosclerose/mortalidade , Azetidinas/uso terapêutico , LDL-Colesterol/sangue , Ensaios Clínicos como Assunto , Colestipol/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Lovastatina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Niacina/uso terapêutico , Modelos de Riscos Proporcionais , Sinvastatina/uso terapêutico , Triglicerídeos/sangue
17.
J Clin Lipidol ; 10(3): 587-93, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27206946

RESUMO

BACKGROUND: Changes in plaque tissue components such as lipid-rich necrotic core (LRNC) and fibrous tissue with long-term statin treatment or discontinuation have not been studied. OBJECTIVE: LRNC and fibrous tissue by magnetic resonance imaging were evaluated in subjects who continued and discontinued statin therapy for 2 years after a prospective study. METHODS: The Rosuvastatin Evaluation of Atherosclerotic Chinese Patients study in 32 lipid treatment naïve subjects showed a significant reduction in LRNC during 24 months of rosuvastatin therapy. After Rosuvastatin Evaluation of Atherosclerotic Chinese Patients was completed, 15 subjects continued taking statins and 17 discontinued despite receiving an instruction to continue statin therapy. LRNC and fibrous tissue were compared between 24 and 48 months within each group and between the 2 groups. RESULTS: At 48 months, LRNC volume and composition decreased significantly compared with that at 24 months in the statin-continued group (101 ± 76 vs 76 ± 65 mm(3); P = .001 and 17.3 ± 11.9% vs 12.6 ± 7.6%; P = .04), whereas fibrous tissue increased significantly in both volume (337 ± 160 vs 357 ± 169 mm(3); P < .001) and composition (76.3 ± 10.5% vs 83.1 ± 10.1%, P = .002). Such changes were not seen in subjects who discontinued statin. Furthermore, the changes in LRNC volume and composition and fibrous tissue composition from 24 to 48 months were significantly different between the statin-continued and -discontinued groups (-25 ± 18 vs 9 ± 14 mm(3); P < .001) and (-4.6 ± 8.2% vs 1.3 ± 2.8%; P = .009) and (6.9 ± 6.8% vs 1.3 ± 5.4%, P = .018). CONCLUSIONS: Continued statin therapy leads to continued decrease in LRNC and increase in fibrous tissue, which indicates improved plaque stability and supports long-term statin therapy.


Assuntos
Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/patologia , Suspensão de Tratamento , Doenças das Artérias Carótidas/diagnóstico por imagem , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem
18.
Data Brief ; 6: 476-81, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26977429

RESUMO

This brief data article summarizes the clinical risk factors and laboratory data of a group of subjects recruited for the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) and an associated magnetic resonance imaging (MRI) substudy. The sample is restricted to those on statin therapy at the time of enrollment and data are presented stratified by whether dynamic contrast enhanced MRI (DCE-MRI) markers of carotid plaque vascularity and inflammation were available or not. The data provided herein are directly related to the article "Longer Duration of Statin Therapy is Associated with Decreased Carotid Plaque Vascularity by Magnetic Resonance Imaging" [2].

19.
Atherosclerosis ; 245: 74-81, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26708287

RESUMO

OBJECTIVE: Plaque neovasculature is a major route for lipoprotein and leukocyte ingress into plaques, and has been identified as a risk factor for carotid plaque disruption. Vp, a variable derived from pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), correlates with plaque neovasculature density. Because lipid-lowering therapy has been associated with regression of neovasculature in animal models, we sought to determine clinical correlates of carotid plaque neovasculature (as assessed by Vp) in participants on statin therapy for established cardiovascular disease. METHODS: 98 participants from an AIM-HIGH sub-study underwent DCE-MRI of their carotid arteries. Expert readers who were blinded to all clinical variables analyzed the MR images to measure carotid plaque Vp in all participants. Associations between Vp and duration of statin therapy and other clinical risk factors were analyzed. RESULTS: Prior duration of statin treatment at enrollment ranged from <1 year (21%) 1-5 years (40%) and >5 years (39%). In univariate analyses, shorter duration of statin therapy (P = 0.01), the presence of metabolic syndrome (P = 0.02), and higher body mass index (P = 0.01) and lipoprotein(a) (P = 0.01) were all significantly associated with higher baseline Vp values. In multivariate analyses, significant associations remained between shorter duration of statin therapy (P = 0.004) and lipoprotein(a) (P = 0.04). CONCLUSIONS: These are the first human, in vivo findings suggesting a relationship between duration of statin therapy and regression of carotid plaque neovasculature. Future longitudinal studies are warranted both to confirm this finding and to address whether changes in neovasculature may translate into change in risk for plaque disruption. CLINICALTRIALS. GOV IDENTIFIERS: NCT00880178, NCT01178320 and NCT00120289.


Assuntos
Artérias Carótidas/patologia , Doenças das Artérias Carótidas/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imagem por Ressonância Magnética/métodos , Neovascularização Patológica/diagnóstico , Placa Aterosclerótica/tratamento farmacológico , Adulto , Doenças das Artérias Carótidas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/patologia , Fatores de Tempo
20.
Heart ; 102(3): 198-203, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26370223

RESUMO

OBJECTIVE: Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new-onset diabetes. METHODS: We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers. We included trials with ≥50 non-diabetic participants and average follow-up of ≥24 weeks. Published data were tabulated and unpublished data sought from investigators. We calculated risk ratios (RR) for new-onset diabetes with random-effects meta-analysis. Heterogeneity between trials was assessed using the I(2) statistic. RESULTS: In 11 trials with 26 340 non-diabetic participants, 1371 (725/13 121 assigned niacin; 646/13 219 assigned control) were diagnosed with diabetes during a weighted mean follow-up of 3.6 years. Niacin therapy was associated with a RR of 1.34 (95% CIs 1.21 to 1.49) for new-onset diabetes, with limited heterogeneity between trials (I(2)=0.0%, p=0.87). This equates to one additional case of diabetes per 43 (95% CI 30 to 70) initially non-diabetic individuals who are treated with niacin for 5 years. Results were consistent regardless of whether participants received background statin therapy (p for interaction=0.88) or combined therapy with laropiprant (p for interaction=0.52). CONCLUSIONS: Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy.


Assuntos
Diabetes Mellitus/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Niacina/uso terapêutico , Quimioterapia Combinada , Dislipidemias/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
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