Comparison of diagnostic utilities of ankle–brachial index and Carotid intima-media thickness as surrogate markers of significant coronary atherosclerosis in Indians

AimWe aimed to compare Ankle–brachial index (ABI) and Carotid intima-media thickness (CIMT) as surrogate markers of significant coronary atherosclerosis in South Indians with coronary artery disease (CAD).Methods and resultsThere were two groups: CAD group (n = 59) and Control group (n = 55). Mean ABI (0.82 ± 0.06 vs. 1.16 ± 0.11, p < 0.0001) and mean CIMT (0.74 ± 0.22 mm vs. 0.45 ± 0.09 mm, p < 0.0001) were statistically different between two groups. ABI < 0.9 (sensitivity: 91.53%, specificity: 100%) and CIMT > 0.63 mm (sensitivity: 61.02%, specificity: 98.18%) implied significant CAD. ABI and CIMT were negatively correlated to one another. With increasing severity of CAD, ABI decreased but CIMT increased.ConclusionABI and CIMT are simple noninvasive tools providing insight into coronary atherosclerosis. They can be done at bedside and easily repeated than coronary angiography. ABI < 0.9 is a better surrogate marker of significant coronary atherosclerosis than CIMT > 0.63 mm in South Indians with CAD.     

Air pollution and cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

Research to date demonstrates a relationship between exposure to ambient air pollutants and cardiovascular disease (CVD). Many studies have shown associations between short-term exposures to elevated levels of air pollutants and CVD events, and several cohort studies suggest effects of long-term exposure on cardiovascular mortality, coronary heart disease events, and stroke. The biologic mechanisms underlying this long-term exposure relationship are not entirely clear but are hypothesized to include systemic inflammation, autonomic nervous system imbalance, changes in vascular compliance, altered cardiac structure, and development of atherosclerosis. The Multi-Ethnic Study of Atherosclerosis provides an especially well-characterized population in which to investigate the relationship between air pollution and CVD and to explore these biologic pathways. This article reviews findings reported to date within this cohort and summarizes the aims and anticipated contributions of a major ancillary study, the Multi-Ethnic Study of Atherosclerosis and Air Pollution.     

骨保护素与动脉粥样硬化和血管钙化

骨保护素(OPG)作为肿瘤坏死因子受体超家族成员,不仅是骨代谢的一个重要调节因子,还是重要的血管调节因子,能够保护血管内皮细胞,抑制血管钙化和动脉粥样硬化。冠状动脉粥样硬化性心脏病(冠心病)及外周动脉硬化疾病血清OPG水平及动脉壁中OPG含量明显升高,OPG在动脉粥样硬化的发生发展中可能起着重要的调节作用。但其确切的机制尚不清楚,可能是一种自我防御代偿机制,以对抗促动脉粥样硬化、血管钙化及血管损伤的其它因子。     

The association between increased carotid intima–media thickness and SYNTAX Score in coronary artery disease: A single center study

BackgroundCarotid artery lesions frequently coexist with coronary arterial disease (CAD). The aim of this study was to investigate the relation between carotid intima-media thickness (CIMT) and the extent of CAD and whether CIMT could be predictive of severity of coronary atherosclerosis.MethodsCoronary angiography and carotid ultrasound evaluations of 100 consecutive patients with CAD who had undergone elective coronary angiography were reviewed. IMT was measured at both carotid arteries. CIMT and severity of CAD relationship based on SYNTAX score was assessed. The relation between CIMT and cardiovascular risk factors was determined.ResultsMean overall SYNTAX score was 15.76 + 4.82. Mean right CIMT was 0.86 ± 0.29 and mean left CIMT was 0.83 ± 0.24. There were no significant correlation between the SYNTAX score and CIMT (r: 10, P: 30). There was significant relationship between hypertension,diabetes and CIMT (P: 0.01).Conclusionwe found no relationship between CIMT and SYNTAX score in patients who underwent coronary angiography. Diabetes mellitus and hypertension are related to increased carotid intima-media thickness.     

Chronic hepatitis C virus infection and atherosclerosis: Clinical impact and mechanisms

Hepatitis C virus(HCV)infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases,which are associated with excess mortality.Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis,heart failure and stroke.In contrast,findings from studies addressing coronary artery disease and HCV have yielded conflicting results.Therefore,meta-analytic reviews and prospective studies are warranted.The pathogenic mechanisms connecting HCV infection,chronic liver disease,and atherogenesis are not completely understood.However,it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls,liver steatosis and fibrosis,enhanced and imbalanced secretion of inflammatory cytokines,oxidative stress,endotoxemia,mixed cryoglobulinemia,perturbed cellular and humoral immunity,hyperhomocysteinemia,hypo-adiponectinaemia,insulin resistance,type 2 diabetes and other components of the metabolic syndrome.Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection.Currently,it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality;moreover,interferon-based treatment appears to decrease the risk of ischemic stroke.     

Association of Lp-PLA2 with digital reactive hyperemia,coronary flow reserve,carotid atherosclerosis and arterial stiffness in coronary artery disease

Background

Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has a powerful inflammatory and atherogenic action in the vascular wall and is an independent marker of poor prognosis in coronary artery disease (CAD). We investigate the association of Lp-PLA2 with markers of vascular dysfunction and atherosclerosis with proven prognostic value in CAD.

Methods

In 111 patients with angiographically documented chronic CAD, we measured 1) carotid intima-media thickness (CIMT), 2) reactive hyperemia using fingertip peripheral arterial tonometry (RH-PAT), 3) coronary flow reserve (CFR), by Doppler echocardiography 4) pulse wave velocity (PWV) and 5) blood levels of Lp-PLA2.

Results

Patients with Lp-PLA2 concentration >234.5 ng/ml (50th percentile) had higher CIMT (1.44 ± 0.07 vs. 1.06 ± 0.06 mm), PWV (11.0 ± 2.36 vs. 9.7 ± 2.38 m/s) and lower RH-PAT(1.24 ± 0.25 vs. 1.51 ± 0.53) and CFR (2.39 ± 0.75 vs. 2.9 ± 0.86) compared to those with lower Lp-PLA (p < 0.05 for all comparisons). Lp-PLA2 was positively associated with CIMT (regression coefficient b: 0.30 per unit of Lp-PLA2, p = 0.02), PWV (b:0.201, p = 0.04) and inversely with RHI-PAT (b: −0.371, p < 0.001) and CFR (b:−0.32, p = 0.002). In multivariate analysis, Lp-PLA2 was an independent determinant of RHI-PAT, CFR, CIMT and PWV in a model including age, sex, smoking, diabetes, dyslipidemia and hypertension (p < 0.05 for all vascular markers). Lp-PLA2, RHI-PAT and CFR were independent predictors of cardiac events during a 3-year follow-up.

Conclusions

Elevated Lp-PLA2 concentration is related with endothelial dysfunction, carotid atherosclerosis, impaired coronary flow reserve and increased arterial stiffness and adverse outcome in CAD patients. These findings suggest that the prognostic role of Lp-PLA2 in chronic CAD may be explained by a generalized detrimental effect of this lipase on endothelial function and arterial wall properties.     

Incidental coronary calcifications on routine chest CT: Clinical implications

Coronary artery calcification (CAC) is a marker of atherosclerosis and an independent risk factor for cardiac-related mortality, with much of the 50% decline in mortality over the past 30 years being attributed to early detection of coronary disease and intervention of modifiable risk factors. With over 10 million computed tomography (CT) examinations of the chest performed in the United States yearly, CAC can be identified in a very large number of patients. In this review, we discuss the clinical evidence underlying the relationship between radiologic identification of CAC, atherosclerosis, and cardiac outcomes and the implications of its assessment on standard chest CT. We conclude that reporting of incidental coronary calcification found on non-gated chest CT would have a great impact on both management and mortality and thus, in the appropriate setting, should be noted in the impression of the radiologic report when identified.     

Coronaryarterycalcificationinchronickidneydisease:Anupdate

Arterial calcification is a well-recognized complication of advanced atherosclerosis.Chronic kidney disease(CKD) is characterized by significantly more pronounced,dis-seminated and fast-progressing calcification of the vascular system,including the coronary arteries.New computed tomography-based imaging techniques al-low for the noninvasive assessment and monitoring of calcification in different vascular sites.Coronary artery calcification(CAC) develops early in the course of CKD and is tightly associated with mineral and bone disor-ders,which include but are not limited to secondary hyperparathyroidism.In this review,recent data on the pathogenesis of CAC development and progression are discussed,with a special emphasis on fibroblast growth factor 23 and its co-receptor,klotho.The prevalence,progression and prognostic significance of CAC are reviewed separately for patients with end-stage renal disease treated with dialysis,kidney transplant recipi-ents and patients with earlier stages of CKD.In the last section,therapeutic considerations are discussed,with special attention paid to the importance of treatment that addresses mineral and bone disorders of CKD.     

EPIDEMIOLOGICAL RISK FACTORS OF CORONARY HEART DISEASE ARE NOT CAUSAL IN ATHEROSCLEROSIS

Logic dictates that for scientific progress in atherogenesis “cause” must be the sole prequisite without which the disease cannot occur. Nor can it be assumed that statistical associations (risk factors) with coronary heart disease (CHD) are causal for atherosclerosis and extrapolations from correlations with CHD incidence to atherosclerosis are invalid. Any factor considered to play a role in atherogenesis requires pathological and experimental evidence consistent with the logic of Koch's specificity of cause and effect. Current epidemiological misuse and manipulation of cause and risk factors are contrary to the basic precepts of scientific logic and the fundamental need for precision in word usage. The term “risk factor”, because of the current deeply entrenched false concept of causality has retarded medical progress and should be abandoned. Its adherents, guilty of a disservice to the tenets of their discipline, have also sullied the scientific integrity of medicine as a whole.     

Serum sclerostin level and its relation to subclinical atherosclerosis in subjects with type 2 diabetes

BackgroundSclerostin, a Wnt-signalling inhibitor, is an established negative regulator of bone formation. However, data regarding its potential importance in vascular disease are less clear. Common carotid artery media thickness (CIMT) assessment and plaque identification using ultrasound imaging are well-recognized tools for identifying and monitoring atherosclerosis. The aim of the present study is to examine the relationship between serum sclerostin and subclinical atherosclerosis (as evidenced by CIMT).MethodsThis cross-sectional study included 50 subjects with T2DM and 20 subjects as a control group. Multivariable linear regression models were used to assess the association of sclerostin with subclinical atherosclerosis.ResultsSerum sclerostin levels in T2DM patients were significantly higher compared to the control group (167.16 ± 63.60 versus 85.98 ± 23.74 pg/ml, P < 0.0001). A concentration of ≥162.5 pg/ml showed a sensitivity of 90% and a specificity of 86.67% to detect an increased risk of subclinical atherosclerosis. Univariate analysis revealed a significant positive correlation between serum sclerostin and CIMT (r = 0.635, P < 0.001). Sclerostin concentrations remained independently associated with CIMT (β = 63.188 [6.919–119.456], P = 0.017) after adjusting for age and gender.ConclusionOur data suggest a positive correlation between serum sclerostin level and subclinical atherosclerosis in subjects with type 2 diabetes mellitus.     

Longitudinal Changes in Vascular Risk Markers and Mortality Rates among a Latino Population with Hypertension

Vascular markers such as pulse-wave velocity and carotid intima-media thickness (CIMT) might improve the prediction of incident cardiovascular disease beyond traditional risk factors. These vascular markers have not been well characterized in minority populations and might be more useful than inflammatory biomarkers. We conducted a prospective, longitudinal cohort study among hypertensive patients in an urban safety-net hospital. We evaluated inflammatory biomarkers, arterial pulse-wave velocity, and carotid intima-media thickness at baseline, 1 year, and 2 years. The primary outcome variable was CIMT. Generalized linear mixed-effects models were used to evaluate associations between CIMT and predictive variables accounting for the correlation of multiple measurements within subjects over time. For our secondary outcome, we used administrative and National Death Index data to determine all-cause death, and univariate relationships were evaluated.Among 175 subjects, 117 were Latino (67%) and 117 were female (67%). Pulse-wave velocity and CIMT regressed over time (both P <0.001) and were highly correlated (P <0.001). Only pulse-wave velocity (P=0.002) and total cholesterol (P=0.03) were associated with CIMT in time-varying covariate analysis. At a median follow-up period of 80 months, 17 of 175 subjects had died (10%). Higher baseline CIMT and pulse-wave velocity were associated with increased mortality rates (both P <0.01). No serum inflammatory marker was significantly correlated with longitudinal changes in CIMT or death. In conclusion, both arterial stiffness and preclinical carotid atherosclerosis were associated with increased mortality rates and might be useful risk-stratification markers among this minority population.     

Autoantibodies against oxidized low density lipoproteins in patients with stable angina, unstable angina or peripheral vascular disease; pathophysiological implications.

BACKGROUND: Antibody antioxidized low density lipoproteins (oxLDL) might play a role both in atherogenesis and in the pathogenesis of acute coronary syndromes. METHODS AND RESULTS: Antibody titres to oxLDL and levels of C-reactive protein were compared in unstable angina, stable angina or peripheral artery disease. Antibody titres to LDL oxidated by CuSO(4)for 2, 4 and 18 h (Cu-oxLDL-Ab(2-4-18)) or by peroxidase (HRP-oxLDL-Ab) were assessed by ELISA. Cu-oxLDL-Ab(2-4-18)were consistently higher in peripheral artery disease than in unstable angina (P<0.001, P<0.001, P=0.01, respectively) or in stable angina (P<0.001, P=0.01, P=ns) but similar in unstable and stable angina. Accordingly, HRP-oxLDL-Ab were higher in peripheral artery disease than in unstable angina (P<0.001) or stable angina (P=0.04) but similar in unstable and stable angina. The number of arterial stenoses was higher in peripheral artery disease than unstable and stable angina (P<0.01). Cu-oxLDL-Ab and HRP-oxLDL-Ab correlated with the severity of atherosclerosis (P<0.01, R=0.4;P=0.02, R=0.3 respectively). Conversely, C-reactive protein levels were higher in unstable than in stable angina (P<0.001) or in peripheral artery disease (P<0.03) but similar in stable angina and peripheral artery disease and did not correlate with the severity of atherosclerosis. CONCLUSION: The autoimmune response to oxLDL is likely to play an important role in atherogenesis but not in precipitating acute coronary syndromes.     

Residence close to high traffic and prevalence of coronary heart disease.

AIMS: Long-term exposure to urban air pollution may accelerate atherogenesis and increase cardiopulmonary mortality. We aim to examine the relationship between the long-term residential exposure to traffic and prevalence of coronary heart disease (CHD). METHODS AND RESULTS: We used baseline data from the German Heinz Nixdorf RECALL study, a population-based, prospective cohort study. For 3399 participants from two cities, we assessed the long-term personal traffic exposure and background air pollution, comparing residents living within 150 m of major roads with those living further away. The principal outcome variable was clinically manifest CHD. We evaluated the association with multivariable logistic regression, controlling for background air pollution and individual level risk factors. Of 3399 participants, 242 (7.1%) had CHD. The crude odds ratio (OR) for prevalence of CHD at high traffic exposure was significantly elevated (1.62, 95%CI 1.12-2.34) and rose to 1.85 (95%CI 1.21-2.84) after adjusting for cardiovascular risk factors and background air pollution. Subgroup analysis showed stronger effects for men (OR 2.33, 95%CI 1.44-3.78), participants younger than 60 years (OR 2.67, 95%CI 1.24-5.74) and never-smokers (OR 2.72, 95%CI 1.40-5.29). CONCLUSION: This study provides epidemiological evidence that the long-term exposure to traffic-related emissions may be an important risk factor for CHD.     

主动脉瓣钙化与冠心病的相关性研究

目的 探讨珠海地区汉族人群主动脉瓣钙化（AVC）与冠心病的相关性.方法 回顾性研究心内科住院患者1140例.所有患者均同期行超声心动图和冠状动脉造影检查,分析AVC与冠心病的相关性.结果 冠心病组中检出AVC的比率明显高于非冠心病组（32.3％比13.8％,P＜0.01）.冠心病组AVC患者冠脉受累严重程度高于无AVC患者.多因素分析显示,AVC、年龄、性别、高脂血症和糖尿病为全组冠心病的独立预测因子（P＜0.05）.结论 AVC与冠心病之间存在显著的相关性,对预测冠心病有一定参考价值.     

Autoantibodies to modified LDLs and other phospholipid-protein complexes as markers of cardiovascular diseases

Recent studies have suggested that antiphospholipid antibodies contribute to the development of atherothrombosis by enhancing atherogenesis and/or by interfering with blood coagulation. The antigenic targets of antiphospholipid antibodies are cardiolipin, oxidized LDL, beta2-glycoprotein I, or prothrombin. Oxidized LDL and beta2-glycoprotein I are found in the atherosclerotic plaque and antibodies to these proteins enhance in vitro the accumulation of modified LDL into macrophages. Autoantibodies binding to modified LDL, cardiolipin and prothrombin have been associated with atherosclerosis and its thrombotic complications in sero-epidemiological studies. These autoantibodies can be used as markers of atherosclerosis but their possible pathogenic role in the athero- and thrombogenesis needs further studies.     

Coronary artery calcification correlates with the presence and severity of valve calcification

Aim

To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both.

Methods

This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score.

Results

AVC was more prevalent than MAC (64% vs. 2.5%, p < 0.001), with 34% having both. Absence of CAC was noted in 12.7% of the study population. AVC + CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC + MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score > 400, and only in 16% had CAC = 0. The same pattern was more evident in individuals with AVC + MAC, where 70% had CAC score > 400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r = 0.28, p = 0.0001), MAC (r = 0.36, p = 0.0001) and with combined AVC + MAC (r = 0.5, p = 0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC.

Conclusion

The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification.     

Air particulate matter and cardiovascular disease: the epidemiological,biomedical and clinical evidence

Air pollution is now becoming an independent risk factor for cardiovascular morbidity and mortality. Numerous epidemiological, biomedical and clinical studies indicate that ambient particulate matter (PM) in air pollution is strongly associated with increased cardiovascular disease such as myocardial infarction (MI), cardiac arrhythmias, ischemic stroke, vascular dysfunction, hypertension and atherosclerosis. The molecular mechanisms for PM-caused cardiovascular disease include directly toxicity to cardiovascular system or indirectly injury by inducing systemic inflammation and oxidative stress in peripheral circulation. Here, we review the linking between PM exposure and the occurrence of cardiovascular disease and discussed the possible underlying mechanisms for the observed PM induced increases in cardiovascular morbidity and mortality.     

Current Understanding of Atherogenesis

Scientific understanding of atherogenesis is constantly developing. From Virchow's observations 160 years ago we now recognize the endothelial response to injury as inflammatory, involved in all stages of atherosclerosis. Endothelial activation may cause reversible injury or dysfunction, or lead to irreparable damage. Indeed, early atherosclerosis is reversible. The introduction of genome-wide association testing has furthered the identification of potentially important genetic variants that help explain the heritability of coronary artery disease as well as spontaneous cases of severe coronary artery disease in patients with otherwise minimal risk factors. However, the mechanisms by which many of the newer variants exert their influence remain unknown.     

Adverse effects of outdoor pollution in the elderly

With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure to ambient air pollution. Few studies have assessed long-term mortality in the elderly. It is still unclear what are the pollutants most damaging to the health of the elderly. It seems that elderly subjects are more vulnerable to particulate matter (PM) than to other pollutants, with particular effect on daily cardio-respiratory mortality and acute hospital admissions. Not many studies have targeted elderly people specifically, as well as specific respiratory morbidity. Most data have shown higher risks in the elderly compared to the rest of the population. Future epidemiological cohort studies need to keep investigating the health effects of air pollutants (mainly cardiopulmonary diseases) on the elderly.     

Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis

The current epidemic of obesity with the associated increasing incidence of insulin resistance, diabetes mellitus and atherosclerosis affecting a large proportion of the North American and Western populations, has generated a strong interest in the potential role of visceral adipose tissue in the development of atherosclerosis and its complications. The intra-abdominal and epicardial space are two compartments that contain visceral adipose tissue with a similar embryological origin. These visceral fats are highly inflamed in obese patients, patients with the metabolic syndrome and in those with established coronary artery disease; additionally they are capable of secreting large quantities of pro-inflammatory cytokines and free fatty acids. There is accumulating evidence to support a direct involvement of these regional adipose tissue deposits in the development of atherosclerosis and its complicating events, as will be reviewed in this article.