Smoking Cessation and Coronary Artery Calcification in CKD

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Coronary Artery Calcification

Coronary artery calcification (CAC) is an established marker of subclinical atherosclerosis and an independent predictor of future coronary heart disease in the asymptomatic primary prevention population, particularly in the intermediate risk cohort. CAC also helps in reclassifying those patients and their risk of cardiovascular events into higher or lower risk categories. MESA (Multi-Ethnic Study of Atherosclerosis) is a National Heart, Lung, and Blood Institute–sponsored population-based medical research study involving 6,814 men and women from 6 U.S. communities without a medical history of clinical cardiovascular disease. The evidence from this population cohort revealed that CAC scoring was independently predictive and highly effective at risk stratification of major adverse cardiac events. This review provides available data based on MESA. We focus on the utility of CAC for cardiovascular disease risk stratification of individuals, and we describe its diagnostic value in identifying patients at risk.     

冠状动脉钙化研究进展

冠状动脉钙化越来越受到重视,发现钙化即意味着亚临床动脉粥样硬化的存在,而动脉硬化不一定都有钙化。通常钙化越严重,冠脉管腔狭窄程度也就越高。但有时二者却缺乏很好的相关性。现就冠脉钙化的发生机制,冠脉钙化及积分与冠心病及其严重程度的关系,冠脉钙化检测方法及积分,血管重构在严重的冠脉钙化却没有明显的管腔狭窄中的作用等方面做一综述。     

冠状动脉钙化研究进展

冠状动脉钙化(CAC)是导致一般人群和冠状动脉性心脏病患者不良结局的危险因素。CAC的发病机制和骨形成有共同的途径,目前已经确定了一些导致CAC发生和发展的危险因素。用药物治疗控制CAC的努力没有取得成功,而冠状动脉钙化的患者经皮冠脉介入术和冠状动脉搭桥术后的无事件生存率也较低。虽然应用药物洗脱支架和斑块修饰装置对钙化血管的预后有一定改善,但不良事件发生率仍然很高。在未来,仍需创新的药物和器械治疗来改善CAC患者的不良预后。     

Coronary Calcification in Patients with Chronic Kidney Disease and Coronary Artery Disease

Background and objectives: A close linkage between chronic kidney disease (CKD) and cardiovascular disease (CVD) has been demonstrated. Coronary artery calcification (CAC) is considered to be the causal link connecting them. The aim of the study is to determine the relationship between level of kidney function and the prevalence of CAC.Design, setting, participants, & measurements: Autopsy subjects known to have coronary artery disease and a wide range of kidney function were studied. Patients without CKD were classified into five groups depending on estimated GFR (eGFR) and proteinuria: eGFR ≥60 ml/min/1.73 m² without proteinuria; CKD1/2: eGFR ≥60 ml/min/1.73 m² with proteinuria; CKD3: 60 ml/min/1.73 m² >eGFR ≥30 ml/min/1.73 m²; CKD4/5: eGFR <30 ml/min/1.73 m²; and CKD5D: on hemodialysis. Intimal and medial calcification of the coronary arteries was evaluated. Risk factors for CVD and uremia were identified as relevant to CAC using logistic regression analysis.Results: Intimal calcification of plaques was present in all groups, but was most frequent and severe in the CKD5D group and less so in the CKD4/5 and CKD3 groups. Risk factors included luminal stenosis, age, smoking, diabetes, calcium-phosphorus product, inflammation, and kidney function. Medial calcification was seen in a small number of CKD4/5 and CKD5D groups. Risk factors were use of calcium-containing phosphate binders, hemodialysis treatment, and duration.Conclusions: It was concluded that CAC was present in the intimal plaque of both nonrenal and renal patients. Renal function and traditional risks were linked to initimal calcification. Medial calcification occurred only in CKD patients.Cardiovascular disease (CVD) is the main cause of morbidity and mortality in patients with end-stage renal disease (ESRD) (1,2) or chronic kidney disease (CKD) (3–7). The mechanisms underlying this increased cardiovascular risk are not clearly understood. In the general population, traditional risk factors for CVD have been well characterized (8), and these are also present in CKD (3–6,9). The mechanisms involved in the connection between CKD and CVD are probably numerous (3–6). Vascular calcification, such as coronary artery calcification (CAC) (10,11), is considered to be the causal link between them.Vascular calcification is common in physiologic and pathologic conditions such as aging, diabetes, dyslipidemia, genetic diseases, and diseases with disturbances of calcium metabolism (12–14). In CKD patients, vascular calcification is even more common, developing early and contributing to the markedly increased cardiovascular risk. Pathomorphologically, atherosclerosis (plaque-forming degenerative changes of the aorta and of large elastic arteries) and arteriosclerosis (concentric medial thickening and hyalinosis of muscular arteries) can be distinguished. Increased knowledge about the mechanisms of calcification together with improved imaging techniques have provided evidence that vascular calcification should be divided into two distinct entities according to the specific site of calcification within the vascular wall: plaque calcification, involving patchy calcification of the intima in the vicinity of lipid or cholesterol deposits, and calcification of the media in the absence of such lipid or cholesterol deposits, known as Mönckeberg-type atherosclerosis (12–14). These two types of calcification may vary in terms of the type of vessel affected, the location along the arterial tree (proximal versus distal), clinical presentation, and treatment and prognosis (12–14). In the general population and in patients with CKD, electron-beam computed tomography (EBCT) has proven CAC as a potent predictor of cardiac events (15–18). Both the prevalence and intensity of CAC are increased in patients with CKD (19–27). Several studies have been undertaken to investigate whether calcification occurs in the intima or media of the coronaries and whether the morphologic details of calcified plaques differ between renal and nonrenal patients (12–14,24). Causal elements for either type of CAC have not been definitively determined (12–14).Autopsy studies are limited in terms of patient selection, but have a major advantage in terms of being able to distinguish intimal from medial calcification. Therefore, our primary goal is to determine whether, among autopsy subjects known to have CAD, there exists a direct relationship between level of kidney function and the prevalence of intimal or medial calcification.     

胰岛素抵抗在冠状动脉粥样硬化性心脏病中的作用及机制

胰岛素抵抗不仅导致胰岛素在促进葡萄糖摄取和利用方面受损,而且在冠状动脉粥样硬化性心脏病的发生和进展过程中起到至关重要的作用。部分冠状动脉粥样硬化性心脏病患者在发病前后出现了明显的胰岛素抵抗现象,治疗过程中降低患者体内的胰岛素抵抗水平能够改善其预后。近年来,越来越多的证据表明二者之间有着密切的联系。现就胰岛素抵抗在冠状动脉粥样硬化性心脏病中可能的作用和机制作一综述。     

冠状动脉钙化研究进展

冠状动脉钙化是动脉粥样硬化的一个重要的危险因素,多项研究揭示冠状动脉钙化和粥样硬化斑块负荷有着密切的关系,因此冠状动脉钙化程度的测量在预测未来心血管事件及死亡率中起着重要的作用。现将通过对冠状动脉钙化的危险因素、发病机制、冠状动脉钙化积分评测及方法、钙化与心血管疾病的关系、冠状动脉钙化与肾脏疾病的关系、冠状动脉钙化与全因死亡及钙化的治疗等方面做一综述。     

冠心病患者病变冠状动脉支数与胰岛素抵抗的关系

目的 通过监测冠心病患者空腹血糖(FPG)、空腹胰岛素(FINS)的水平,并根据这两项结果计算胰岛素敏感指数(ISI)、稳态模型的胰岛素抵抗指数(HOMA-IR),了解患者是否存在胰岛素抵抗(IR);通过冠状动脉造影了解冠状动脉病变支数,了解IR与冠状动脉病变程度的关系.方法 本文收集了ST段抬高型心肌梗死(STEMI)患者19例,非ST段抬高型心肌梗死(NSTEMT)患者15例,不稳定型心绞痛者(UAP)18例,稳定型心绞痛者(SAP)16例,健康对照者(CO)20例.各组患者均在入院24h内抽取清晨安静平卧状态下的空腹肘静脉血,其中留取血清标本测定FPG、FINS.结果 ISI与病变冠状动脉支数无一定的关系.结论 IR在冠心病患者中普遍存在,且随着患者病情的加重IR更明显,胰岛素抵抗程度与冠心病患者病变冠状动脉支数无关.     

Myocardial Flow Reserve and Coronary Calcification in Prognosis of Patients With Suspected Coronary Artery Disease

ObjectivesThe aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).BackgroundAdvances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.MethodsConsecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables.ResultsA total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.)ConclusionsIn this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.     

High Prevalence of Intracranial Artery Calcification in Stroke Patients with CKD: A Retrospective Study

Background and objectives: Intracranial artery calcification (IAC) is frequently observed on brain computed tomography (CT) scans in stroke patients. This retrospective study was designed to determine the prevalence, risk factors, and clinical relevance of IAC in a cohort of patients with ischemic stroke.Design, setting, participants, & measurements: We included all eligible patients admitted to Amiens University Hospital for acute ischemic stroke between January and December 2006 and assessed using 64-slice multidetector-row CT (n = 340). Patients were classified according to the presence or absence of IAC in the internal carotid arteries, middle cerebral arteries, vertebral arteries, and basilar artery. GFR was estimated using the MDRD equation. Chronic kidney disease (CKD) was defined as a GFR < 60 ml/min/1.73 m². We also studied a control group of patients admitted for neurologic diseases other than stroke.Results: Two hundred fifty-nine stroke patients (76.2%) displayed IAC, which was independently associated with carotid atherosclerosis > 50%, age, and GFR. One hundred three nonstroke patients (60.2%) had IAC, with age, arterial hypertension, and GFR as independently associated factors. For all patients taken together, age, arterial hypertension, stroke, and GFR were independently associated with IAC.Conclusion: These results confirm the high prevalence of IAC in patients with and without ischemic stroke and show for the first time that IAC is associated with the presence of CKD in these patients. The frequency of IAC was significantly higher in stroke patients than in nonstroke patients. The association between IAC and stroke outcome requires further investigation.Vascular calcification is widely acknowledged to be an integral part of the atherosclerotic process and occurs in 80 to 90% of atheromatous lesions (1). Arterial calcifications have a number of adverse hemodynamic consequences that can cause cardiac, vascular, and brain diseases (2). Several studies have demonstrated that atherosclerosis in end-stage renal disease patients and in patients with less advanced CKD is more frequent than in the general population (reviewed by Vanholder et al. [3]). Furthermore, exacerbated atherosclerotic disease in patients with CKD is characterized by a high degree of medial and intimal calcification (4,5). The mechanisms by which CKD may increase vascular calcification have not been elucidated but may include factors associated with a decline in renal function, i.e., anemia, oxidative stress (6), deregulation in calcium-phosphate homeostasis, inflammatory syndrome (7), decreased nitric oxide availability (8), and conditions promoting coagulation.Arterial calcification is an easily identifiable marker. In clinical practice, the methods used to assess vascular calcification in CKD patients include standard radiography of the aorta and iliac arteries (9,10) and echocardiography of the heart valves (11). Furthermore, the sensitive, reliable assessment of coronary artery calcification using multi-detector-row computed tomography (MDCT) (12,13) constitutes a significant step forward in the routine detection of coronary artery disease.Vascular calcification can also be assessed in various peripheral sites from plain radiographs of the hands (9) and a head CT scan (14). Indeed, intracranial artery calcification (IAC) is frequently observed on head CT scans in stroke patients (14–16). However, the link between IAC and atherosclerosis has not been evaluated. Moreover (and to the best of our knowledge), no report has evaluated the impact of CKD on the pathogenesis of IAC. Lastly, the predictive value for IAC on the patient''s outcome has not been determined. The aim of the present study was therefore to evaluate the prevalence, risk factors, and clinical relevance of IAC in a retrospective study of a cohort of ischemic stroke patients.     

冠状动脉瘤样扩张与电子束CT检测的冠状动脉钙化

为探讨冠状动脉瘤样扩张患者电子束CT检测的冠状动脉钙化的特点及其临床和病理意义 ,将 2 7例经选择性冠状动脉造影确诊的冠状动脉瘤样扩张患者行电子束CT检查以计算钙化积分 ,并与 2 7例年龄和性别匹配的冠状动脉造影正常者进行比较。结果发现 ,冠状动脉瘤样扩张组钙化阳性率、钙化积分中位数及钙化积分的自然对数转换值均显著高于正常对照组 (P <0 .0 1或 0 .0 0 1)。冠状动脉瘤样扩张组中 2 1例粥样硬化性瘤样扩张患者钙化阳性率为 81.0 % ;弥漫性扩张动脉的钙化积分对数转换值显著低于局限性扩张动脉 (1.2 2± 1.79比 2 .86± 1.85 ,P <0 .0 5 )。结果提示 ,粥样硬化性冠状动脉瘤样扩张患者多数存在较为广泛的冠状动脉钙化 ,且钙化程度与病变类型有关。     

胰岛素抵抗和高敏C反应蛋白在非糖尿病患者冠心病发病中的作用

目的:探讨非糖尿病患者胰岛素抵抗(IR)、高敏C反应蛋白(hsCRP)在冠心病发病中的作用.方法:将连续608例非糖尿病患者,根据冠脉造影结果分为冠心病组(334例)和对照组(274例).测定代谢参数和hsCRP,并用自我平衡模型分析法(HOMA)指数(IRI)评价胰岛素抵抗,进行相关数理统计.结果:冠心病组的年龄、空腹血浆胰岛素、平均IRI、hsCRP、脂蛋白a、血肌酐、血清肌酐清除率、左心室射血分数、高血压、男性、吸烟、IRII≥2.69以及既往血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB)应用比例均显著高于对照组,差异有统计学意义(P<0.05～0.01),高密度脂蛋白显著低于对照组,差异有统计学意义(P<0.01).多因素Logistic回归分析提示,男性、高龄(≥65岁)、IRI≥2.69、hsCRP≥10 mg/L、脂蛋白a≥0.22 g/L和血肌酐≥100umol/L,为冠心病独立危险因素(P均<0.05).综合各种危险因素的受试者工作曲线(ROC)下面积为0.750(P<0.01);hsCRP的ROC曲线下面积为0.685(P<0.01).IRI与冠心病发生呈显著正相关(P<0.01).结论:即使非糖尿病患者,胰岛素抵抗和hsCRP升高等仍为冠心病的独立危险因素.     

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

Background and objectives: Recent in vitro studies have shown a link between alkaline phosphatase and vascular calcification in patients with chronic kidney disease (CKD). High serum levels of alkaline phosphatase are associated with increased death risk in epidemiologic studies of maintenance hemodialysis (MHD) patients. We hypothesized that coronary artery calcification is independently associated with increased serum alkaline phosphatase levels in MHD patients.Design, setting, participants, & measurements: We examined the association of coronary artery calcification score (CACS) and alkaline phosphatase in 137 randomly selected MHD patients for whom markers of malnutrition, inflammation, and bone and mineral disorders were also measured.Results: Serum alkaline phosphatase was the only measure with significant and robust association with CACS (P < 0.003), whereas either other biochemical markers had no association with CACS or their association was eliminated after controlling for case-mix variables. Serum alkaline phosphatase >120 IU/L was a robust predictor of higher CACS and was particularly associated with the likelihood of CACS >400 (multivariate odds ratio 5.0 95% confidence interval 1.6 to 16.3; P = 0.007). Serum alkaline phosphatase of approximately 85 IU/L seemed to be associated with the lowest likelihood of severe coronary artery calcification, but in the lowest tertile of alkaline phosphatase, the CACS predictability was not statistically significant.Conclusions: An association between serum alkaline phosphatase level and CACS exists in MHD patients. Given the high burden of vascular calcification in patients with CKD, examining potential therapeutic interventions to modulate the alkaline phosphatase pathway may be warranted.Vascular calcification is common in individuals with chronic kidney disease (CKD) and is a significant correlate of the high cardiovascular death risk (1–3). Both intimal and medial calcification are observed frequently in patients with CKD (4–7). Several mechanisms have been implicated for the high prevalence of vascular calcification in CKD, including the high burden of conventional cardiovascular risks such as diabetes, hypertension, and dyslipidemia; bone and mineral disorders such as calcium load and secondary hyperparathyroidism (SHPT); chronic inflammation such as high level of proinflammatory cytokines; and deficiency of anticalcemic factors such as fetuin (8,9). Lomashvili et al. (5) reported that vascular damage can induce expression of tissue-nonspecific alkaline phosphatase (AlkPhos), which per se hydrolyzes and inactivates inorganic pyrophosphates, a process that can enhance vascular calcification. We recently showed that higher serum AlkPhos levels in maintenance hemodialysis (MHD) patients were independently associated with increased all-cause and cardiovascular mortality in approximately 74,000 MHD patients, even after adjustment for surrogates of nutrition, inflammation, minerals, serum parathyroid hormone (PTH), and liver enzymes (10). Nevertheless, the pathophysiologic link between increased AlkPhos level and mortality in MHD patients is not clear. Given the recent in vitro findings about the link between AlkPhos and vascular calcification via the pyrophosphate pathway, we hypothesized that the increased cardiovascular and all-cause death risk observed in the setting of high serum AlkPhos level may be related to vascular calcification in MHD patients (6,11). To test this hypothesis, we examined the association of serum AlkPhos and coronary artery calcification in a cohort of MHD patients for whom other risk factors of cardiovascular disease including inflammatory markers were also examined.