Smoking Cessation and Coronary Artery Calcification in CKD

Open in a separate window     

冠状动脉钙化的机制研究进展

冠状动脉钙化在动脉粥样硬化晚期出现,是冠状动脉粥样硬化的标志,也与临床意义上的冠状动脉疾病相关。临床检测到的钙化程度能反映斑块稳定状态,且能预测未来的心血管事件。冠状动脉钙化在病理上始于微钙化,然后生长成较大的钙碎片,最终导致片状沉积,这种演变与斑块的进展同时发生。本综述系统总结了冠状动脉启动钙化的两种细胞机制,并归纳了参与影响钙化进程的调节因素,同时重点讨论脂蛋白(a)和维生素K如何参与调节钙化进程,还总结了现有的特异性药物治疗以及潜在靶点,为防治冠状动脉钙化以及预防心血管事件提供了一定参考价值。     

Relationship between Kidney Function and Subclinical Atherosclerosis Progression Evaluated by Coronary Artery Calcification

Aims: The roles of urinary albumin, eGFRcystatin (eGFRcys), and eGFRcreatinine (eGFRcre) in the progression of coronary artery calcification (CAC) remain unclear. Therefore, the present study investigated the relationship between kidney function and CAC progression. Methods: A total of 760 Japanese men aged 40-79 years were enrolled in this population-based study. Kidney function was measured using eGFRcre, eGFRcys, and the urine albumin-to-creatinine ratio. CAC scores were calculated using the Agatston method. CAC progression was defined as an annual increase of ＞10 Agatston units (AU) among men with 0＜CAC＜100 AU at baseline, that of ＞10% among those with CAC ≥ 100 AU, and any progression for those with CAC=0 at baseline. The relative risk (RR) of CAC progression based on kidney function was assessed using a robust Poisson regression model. Results: The mean follow-up period was 4.9 years. CAC progression was detected in 45.8% of participants. Positive associations between CAC progression and albuminuria (＞30mg/g) (RR: 1.29; 1.09 to 1.53;p=0.004) and low eGFRcys (＜60ml/min/1.73m²) (RR: 1.27; 1.05 to 1.53;p=0.012) remained significant after adjustments for age, the follow-up time, and computerized tomography type. Following further adjustments for hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and lifestyle factors, CAC progression was associated with albuminuria (RR: 1.20; 1.01 to 1.43;p=0.04) and low eGFRcys (RR: 1.19; 0.99 to 1.43;p=0.066), but not with eGFRcre. Conclusion: CAC progression was associated with albuminuria; however, its relationship with eGFRcys was weakened by adjustments for risk factors.     

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。     

Sex Differences in Coronary Artery and Thoracic Aorta Calcification and Their Association With Cardiovascular Mortality in Heavy Smokers

ObjectivesThe aim of this study was to investigate sex differences in the prevalence, extent, and association of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) scores with cardiovascular mortality in a population eligible for lung screening.BackgroundCAC and TAC scores derived from chest computed tomography (CT) might be useful biomarkers for individualized cardiovascular disease prevention and could be especially relevant in high-risk populations such as heavy smokers. Therefore, it is important to know the prevalence of arterial calcifications in male and female heavy smokers, and if there are differences in the predictive value calcifications carry.MethodsWe performed a nested case–control study with 5,718 participants of the CT arm of the NLST (National Lung Screening Trial). Prevalence and extent of CAC and TAC were resampled to the full cohort to provide unbiased estimates of the typical calcium burden of male and female heavy smokers. Weighted Cox proportional hazards regression was used to assess differences in the association of CAC and TAC scores with all-cause and cardiovascular mortality.ResultsCAC was substantially more common and more severe in men (prevalence: 81% vs. 60%; median volume: 104 mm³ vs. 12 mm³). Women had CAC comparable to that of men who were 10 years younger. TAC was equally common in men and women, with a tendency to be more pronounced in women (prevalence: 92% vs. 93%; median volume: 388 mm³ vs. 404 mm³). Both types of calcification were associated with increased cardiovascular and all-cause mortality. TAC scores improved the prediction of coronary heart disease mortality over CAC in men, but not in women. In both sexes, TAC, but not CAC, was associated with cardiovascular mortality other than coronary heart disease.ConclusionsCAC develops later in women, whereas TAC develops equally in both sexes. CAC is strongly associated with coronary heart disease, whereas TAC is especially associated with extracardiac vascular mortality in either sex.     

Higher Fibrinogen Levels Predict Progression of Coronary Artery Calcification in Adults with Type 1 Diabetes

Aim

To determine whether fibrinogen levels predict independently progression of coronary artery calcification (CAC) in adults with type 1 diabetes.

Methods

Data from a prospective cohort - the Coronary Artery Calcification in Type 1 Diabetes Study - were evaluated. Fibrinogen levels at baseline were separated into quartiles. CAC was measured twice and averaged at baseline and at follow-up 2.4 ± 0.4 years later. CAC progressors were defined as participants whose square-root transformed CAC volume increased by ≥2.5 mm³ or development of clinical coronary artery disease during the follow-up period.

Results

Fibrinogen levels were higher in progressors than in non-progressors (276 ± 61 mg/dl versus 259 ± 61 mg/dl, p = 0.0003). CAC progression, adjusted for known cardiovascular risk factors, increased in the highest quartile.

Conclusions

Higher fibrinogen levels predict CAC progression in type 1 diabetes subjects, independent of standard cardiovascular risk factors.     

Pulse Pressure and Presence of Coronary Artery Calcification

Background: Coronary calcification (CAC) is found in early stages of CKD. Pulse pressure (PP) predicts CAC in dialysis patients. This study evaluates the accuracy of PP in predicting CAC in patients not yet on dialysis (CKD patients).Methods: CKD patients (n = 388) underwent coronary calcium score (CAC score) and abdominal x-ray (n = 128) for estimating aorta calcification (AAC). Biochemistry and PP were measured every 3 and 6 months in patients with stage 4 to 5 and 2 to 3 CKD, respectively. The accuracy of PP and AAC was assessed by receiver operating characteristics analysis.Results: PP correlated with CAC score in the whole cohort and in patients with stages 2 to 3 and stages 4 to 5 CKD. PP >60 mmHg predicted CAC score >0 (OR: 2.14; P < 0.001), ≥100 (OR: 2.92; P < 0.001), ≥400 (OR: 6.17; P < 0.001) after multivariable adjustment. Area under the curve (AUC) was 0.626 for CAC score >0, 0.676 for score >100, and 0.746 for score >400. PP >60 mmHg reduced the rate of event-free survival. AAC was found in 58% of patients and correlated with CAC score. AUC was 0.628 for CAC score >0, 0.652 for score >100, 0.831 for score >400.Conclusion: PP may identify CKD patients with subclinical CAC who need further evaluation. Accuracy of PP and AAC is nearly similar in predicting CAC. High PP indicates vessel wall alterations leading to adverse outcome.Coronary artery calcification (CAC) is present even in asymptomatic patients with stage 2 to 5 of chronic kidney disease (CKD) who are not yet on dialysis (1–3). The disease progresses rapidly and is associated with fatal and nonfatal cardiovascular events (4,5). It is likely that in CKD patients, who frequently die from coronary heart disease before dialysis initiation, CAC is an important risk factor for cardiovascular events as in patients on dialysis (ESRD patients) (6–9). However, unanswered questions are (1) how to distinguish CKD patients who may have CAC and need further cardiovascular tests and early therapeutic intervention and (2) what procedure should be used for the preliminary screening.The numbers of patients with stages 2 to 5 of CKD are increasing worldwide (10,11), and CAC is found in less than half of this population (1–3). In addition, gold standard procedures such as electron beam or multislice computed tomography (EBCT or MSCT) are not suitable for screening large population (12–14); EBCT is available in only few nephrology units and is expensive, MSCT is time consuming and exposes patients to large radiation doses. Therefore, in CKD patients, it is important to find simple and inexpensive tests for the preliminary screening. Standard radiographs, echocardiography, and pulse pressure may predict the presence of CAC in ESRD patients (15–18).The aim of the present study was to evaluate the diagnostic accuracy of pulse pressure in predicting the presence of CAC in CKD patients. To our knowledge, no data are available on this issue.     

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.     

早发冠心病患者危险因素与冠状动脉病变的关系

目的探讨早发冠心病患者吸烟与冠状动脉病变的关系及其意义。方法选取经冠状动脉造影确诊的PCAD患者270例,其中男性158例、女性112例,采集患者吸烟史（吸烟年数、每日吸烟支数）、血脂水平（HDL—C、LDL—C、TG、TC）,记录患者冠状动脉造影结果。同时进行相关性分析。结果吸烟指数与冠状动脉慢血流之间存在正相关（r=0．156,P〈0．05）;HDL—C与吸烟指数及Gensini积分均呈负相关（r=-0．136、-0．156,均P〈0．01）;吸烟指数与Gensini积分之间无线性相关关系（r=0．084,P〉0．05）。结论早发冠心病患者吸烟与HDL—C水平下降和冠状动脉慢血流现象相关。     

生活方式对冠状动脉钙化的影响

通过CT检测的冠状动脉钙化（CAC）是冠状动脉粥样硬化的标志,其与发生冠心病和其他心血管事件明确相关;CAC除了受到性别、糖尿病、高血压、高血脂等情况影响外,生活方式例如吸烟、饮用咖啡、茶等也可以影响CAC。明确生活方式对CAC的影响,就可以为预防CAC的发生及进展提供重要的方法。     

Low Skeletal Muscle Mass Is Associated With the Presence,Incidence, and Progression of Coronary Artery Calcification

BackgroundLow skeletal muscle mass (SMM) is an emerging risk factor of cardiovascular disease (CVD). We investigated the association between SMM and coronary artery calcification (CAC).MethodsWe enrolled 19,728 adults free of CVD who underwent computed tomographic estimation of Agatston CAC scores for cross-sectional analysis. Among them, 5,401 subjects who had at least 2 follow-up CAC scores were included in longitudinal analysis. Relative SMM is presented as the skeletal muscle mass index [SMI (%) = total appendicular muscle mass (kg)/body weight (kg) × 100]. CAC presence and incidence were defined as CAC score > 0, and CAC progression was defined as √CAC score (follow-up) − √CAC score (baseline) > 2.5.ResultsAmong all of the subjects (mean age 53.4 years, 80.8% male), the prevalence of CAC was 36.7%. The incidence of CAC was 17.4% during a mean of 3.6 years, and the progression of CAC was 49.9% during a mean of 2.3 years. The lowest SMI quartile was significantly associated with an increased risk of CAC presence (adjusted odds ratio 2.75, 95% confidence interval [CI] 2.45-3.05; P < 0.001), incidence (adjusted hazard ratio [AHR] 1.99, 95% CI 1.36-2.91; P < 0.001), and progression (AHR 1.48, 95% CI 1.25-1.77; P < 0.001) compared with the highest quartile. SMI as a continuous value was also significantly inversely associated with CAC. SMI was the best parameter to be related to CAC among other quantitative indices such as height or body mass index adjusted.ConclusionsLow SMM is significantly associated with an elevated risk of CAC, independently of other cardiometabolic parameters.     

Screening and Risk Stratification of Coronary Artery Disease in End-Stage Renal Disease

End-stage renal disease (ESRD) is a growing global health problem with major health and economic implications. Cardiovascular complication is the major cause of morbidity and mortality in this population. Clustering of traditional atherosclerotic risk factors, such as diabetes, systemic inflammation, and altered mineral metabolism, contributes to enhanced systemic atherosclerosis in patients with ESRD. Prevalence of obstructive coronary artery disease (CAD) on coronary angiography exceeds 50% in this population. Despite having extensive CAD and vascular disease, patients with ESRD often do not present with classic symptoms because of impaired exercise capacity and diabetes. Furthermore, clinical trial data are exceedingly lacking in this population, resulting in considerable clinical equipoise regarding the optimal approach to the identification and subsequent management of CAD in these patients. Traditional clinical screening tools, including conventional risk prediction models, are significantly limited in their predictive accuracy for cardiovascular events in patients with ESRD. Noninvasive cardiac stress imaging modalities, such as nuclear perfusion and echocardiography, have been shown to improve the traditional clinical model in identifying the presence of CAD. Furthermore, they add incremental prognostic information to angiographic data. Novel imaging techniques and biomarker assays hold significant promise in further improving the ability to identify and risk-stratify for CAD. This review focuses on the current understanding of the clinical risk profile of asymptomatic patients with ESRD with an emphasis on the strengths and limitations of various noninvasive cardiovascular imaging modalities, including the role of novel methods in refining risk prediction. In addition, issues and challenges pertaining to the optimal timing of initial risk assessment (“screening”) and possible repeat screening (“surveillance”) are addressed. We also summarize the current data on the approach to the patient with ESRD being evaluated for transplantation in the context of recent guidelines and position statements by various professional societies.