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Coronary artery calcium score and risk of cardiovascular events without established coronary artery disease: a systemic review and meta-analysis.
Abuzaid, A, Saad, M, Addoumieh, A, Ha, LD, Elbadawi, A, Mahmoud, AN, Elgendy, A, Abdelaziz, HK, Barakat, AF, Mentias, A, et al
Coronary artery disease. 2021;(4):317-328
Abstract
BACKGROUND Coronary artery calcium (CAC) is an indicator of atherosclerosis, and the CAC score is a useful noninvasive assessment of coronary artery disease. OBJECTIVE To compare the risk of cardiovascular outcomes in patients with CAC > 0 versus CAC = 0 in asymptomatic and symptomatic population in patients without an established diagnosis of coronary artery disease. METHODS A systematic search of electronic databases was conducted until January 2018 for any cohort study reporting cardiovascular events in patients with CAC > 0 compared with absence of CAC. RESULTS Forty-five studies were included with 192 080 asymptomatic 32 477 symptomatic patients. At mean follow-up of 11 years, CAC > 0 was associated with an increased risk of major adverse cardiovascular and cerebrovascular events (MACE) compared to a CAC = 0 in asymptomatic arm [pooled risk ratio (RR) 4.05, 95% confidence interval (CI) 2.91-5.63, P < 0.00001, I2 = 80%] and symptomatic arm (pooled RR 6.06, 95% CI 4.23-8.68, P < 0.00001, I2 = 69%). CAC > 0 was also associated with increased risk of all-cause mortality in symptomatic population (pooled RR 7.94, 95% CI 2.61-24.17, P < 0.00001, I2 = 85%) and in asymptomatic population CAC > 0 was associated with higher all-cause mortality (pooled RR 3.23, 95% CI 2.12-4.93, P < 0.00001, I2 = 94%). In symptomatic population, revascularization in CAC > 0 was higher (pooled RR 15, 95% CI 6.66-33.80, P < 0.00001, I2 = 72) compared with CAC = 0. Additionally, CAC > 0 was associated with more revascularization in asymptomatic population (pooled RR 5.34, 95% CI 2.06-13.85, P = 0.0006, I2 = 93). In subgroup analysis of asymptomatic population by gender, CAC > 0 was associated with higher MACE (RR 6.39, 95% CI 3.39-12.84, P < 0.00001). CONCLUSION Absence of CAC is associated with low risk of cardiovascular events compared with any CAC > 0 in both asymptomatic and symptomatic population without coronary artery disease.
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Prognostic value of coronary artery calcium score in symptomatic individuals: A meta-analysis of 34,000 subjects.
Lo-Kioeng-Shioe, MS, Rijlaarsdam-Hermsen, D, van Domburg, RT, Hadamitzky, M, Lima, JAC, Hoeks, SE, Deckers, JW
International journal of cardiology. 2020;:56-62
Abstract
BACKGROUND Coronary artery calcium (CAC) scanning has evolved into an important subclinical prediction method for cardiovascular diseases in asymptomatic subjects. However, the prognostic implication of CAC scanning in symptomatic individuals is less clear. OBJECTIVES To assess the prognostic utility of CAC in predicting risk of major adverse cardiac events (MACE) in stable patients with suspected CAD. METHODS We did a systematic electronic literature search for studies presenting original data in CAC score, and reporting cardiovascular events in stable, symptomatic patients as primary outcome. Primary outcome of the meta-analysis was the occurrence of MACE, a composite of late coronary revascularization, hospitalization for unstable angina or heart failure, nonfatal myocardial infarction, and cardiac death or all-cause mortality. Using random effects models, we pooled relative risk ratios of CAC for MACE, and adjusted hazard ratios (HR) of the associations between different CAC strata (CAC 0-100,100-400, and ≥ 400, versus CAC = 0) and incident MACE. RESULTS We included 19 observational studies (n = 34,041). In total, 1601 events were analyzed, of which 158 in patients with CAC = 0. The pooled relative risk ratio was 5.71 (95%-CI: 3.98;8.19) for subjects with CAC > 0. The pooled estimate of adjusted HRs demonstrated increasing, positive associations, with the strongest association for CAC > 400 (HR: 4.88; 95%-CI: 2.44;9.27). CONCLUSIONS This meta-analysis demonstrated that increased levels of CAC are strongly and independently associated with increased risk for MACE in stable, symptomatic patients with suspected CAD, showing increasing risk with greater CAC scores. Application of CAC scanning as a prediction method could be useful for a considerable number of such patients.
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The Relationship of Coronary Artery Calcium and Clinical Coronary Artery Disease with Cognitive Function: A Systematic Review and Meta-Analysis.
Xia, C, Vonder, M, Sidorenkov, G, Oudkerk, M, de Groot, JC, van der Harst, P, de Bock, GH, De Deyn, PP, Vliegenthart, R
Journal of atherosclerosis and thrombosis. 2020;(9):934-958
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Abstract
AIM: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. METHODS A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). RESULTS Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6-12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17-1.48) with substantial heterogeneity (I2=87.0%, p<0.001). Pooled HR of CAD for incident MCI/dementia over 3.2-25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24-1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. CONCLUSIONS Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.
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Comparison of regadenoson and nitroprusside to adenosine for measurement of fractional flow reserve: A systematic review and meta-analysis.
Lee, JZ, Singh, N, Nyotowidjojo, I, Howe, C, Low, SW, Nguyen, T, Pinto, D, Kumar, G, Lee, KS
Cardiovascular revascularization medicine : including molecular interventions. 2018;(2):168-174
Abstract
BACKGROUND FFR is useful in defining the physiological significance of intermediate coronary stenosis and requires induction of maximal hyperemia and measurement of pressure proximal and distal to the stenosis. Hyperemia normally is induced by either IV or IC adenosine, a medication associated with short-term side effects. IV regadenoson and IC nitroprusside have been suggested as viable alternatives. This meta-analysis aims to identify all studies comparing use of intravenous (IV) regadenoson or intracoronary (IC) nitroprusside with IV adenosine to determine differences related to the agent utilized for assessment of fractional flow reserve (FFR). METHODS We searched PubMed, EMBASE, Web of Science, SCOPUS, ClinicalTrials.gov and the Cochrane Library databases for studies comparing IV regadenoson or IC nitroprusside to IV adenosine for FFR assessment. The main outcome was difference in mean FFR measurement. The main secondary outcomes were composite side-effect profile and reclassification of lesions. RESULTS Seven studies were included in the analysis, with a total of 375 patients. Compared to IV adenosine, there was no difference in the mean FFR derived from IV regadenoson (p=1.0) or IC nitroprusside (p=0.48). IV regadenoson was associated with 53% lower risk of pooled side effects compared to IV adenosine (p=0.05). IC nitroprusside was associated with 97% lower risk of pooled side effects compared to IV adenosine (p<0.001). CONCLUSIONS IV regadenoson and IC nitroprusside produce similar pressure-derived FFR measurements compared to IV adenosine and have a favorable side effect profile. Both can be considered as alternative agents to IV adenosine for FFR measurement. Further clinical validation is warranted.
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The Identification of Calcified Coronary Plaque Is Associated With Initiation and Continuation of Pharmacological and Lifestyle Preventive Therapies: A Systematic Review and Meta-Analysis.
Gupta, A, Lau, E, Varshney, R, Hulten, EA, Cheezum, M, Bittencourt, MS, Blaha, MJ, Wong, ND, Blumenthal, RS, Budoff, MJ, et al
JACC. Cardiovascular imaging. 2017;(8):833-842
Abstract
OBJECTIVES The aim of this study was to assess the odds of initiation or continuation of pharmacological and lifestyle preventive therapies in patients with nonzero versus zero coronary artery calcium (CAC) score detected on cardiac computed tomography. BACKGROUND Detection of calcified coronary plaque could serve as a motivational tool for physicians and patients to intensify preventive therapies. METHODS We searched PubMed, EMBASE (Excerpta Medica database), Web of Science, Cochrane CENTRAL (Cochrane central register of controlled trials), ClinicalTrials.gov, and the International Clinical Trials Registry Platform for studies evaluating the association of CAC scores with downstream pharmacological or lifestyle interventions for prevention of cardiovascular disease. Pooled odds ratios (ORs) of downstream interventions were obtained using the DerSimonian and Laird random effects model. RESULTS After a review of 6,256 citations and 54 full-text papers, 6 studies (11,256 participants, mean follow-up time: 1.6 to 6.0 years) were included. Pooled estimates of the odds of aspirin initiation (OR: 2.6; 95% confidence interval [CI]: 1.8 to 3.8), lipid-lowering medication initiation (OR: 2.9; 95% CI: 1.9 to 4.4), blood pressure-lowering medication initiation (OR: 1.9; 95% CI: 1.6 to 2.3), lipid-lowering medication continuation (OR: 2.3; 95% CI: 1.6 to 3.3), increase in exercise (OR: 1.8; 95% CI: 1.4 to 2.4), and dietary change (OR: 1.9; 95% CI: 1.5 to 2.5) were higher in individuals with nonzero CAC versus zero CAC scores, but not for aspirin or blood pressure-lowering medication continuation. When assessed within individual studies, these findings remained significant after adjustment for baseline patient characteristics and cardiovascular risk factors. CONCLUSIONS This systematic review and meta-analysis suggests that nonzero CAC score, identifying calcified coronary plaque, significantly increases the likelihood of initiation or continuation of pharmacological and lifestyle therapies for the prevention of cardiovascular disease.
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Prognostic value of segment involvement score compared to other measures of coronary atherosclerosis by computed tomography: A systematic review and meta-analysis.
Ayoub, C, Erthal, F, Abdelsalam, MA, Murad, MH, Wang, Z, Erwin, PJ, Hillis, GS, Kritharides, L, Chow, BJW
Journal of cardiovascular computed tomography. 2017;(4):258-267
Abstract
BACKGROUND The segment involvement score (SIS) is a semiquantitative measure of the extent of atherosclerosis burden by coronary computed tomography angiography (CTA). We sought to evaluate by meta-analysis the prognostic value of SIS, and to compare it with other CTA measures of coronary artery disease (CAD). METHODS Electronic databases from 1946 to January 2016 were searched. Studies reporting SIS, or an equivalent measure by coronary CTA, and clinical outcomes were included. Maximally adjusted hazard ratios (HR), predominantly for clinical variables, were extracted for SIS, obstructive CAD, Agatston coronary artery calcium score, and plaque composition. These were pooled using DerSimonian-Laird random effects models. RESULTS Eleven nonrandomized studies with good methodological quality enrolling 9777 subjects (mean age 61 ± 11 years, 57% male, mean follow up 3.3 years) who had 472 (4.8%) MACE (cardiac or all cause death, non-fatal myocardial infarction or late revascularization), were included. SIS (per segment increase) had pooled HR of 1.25 (95% CI: 1.16,1.35; I2 = 71.4%, p < 0.001) for MACE. HR for MACE was 1.37 (95% CI: 1.32,1.42; I2 = 95.6%, p < 0.001) for number of segments with stenosis (per segment increase), 3.39 (95% CI: 1.65,6.99; I2 = 87.8%, p = 0.001) for obstructive CAD (binary variable) and 1.00 (95% CI: 1.00,1.01; I2 = 75.0%, p = 0.490) for Agatston score (per unit increase). HRs by plaque composition (calcified, non-calcified and mixed; per segment change) were 1.24 (95% CI: 1.10,1.39; I2 = 81.6%, p = 0.001), 1.20 (95% CI: 0.97,1.48; I2 = 92.9%, p = 0.093) and 1.27 (95% CI: 1.03,1.58; I2 = 89.8%, p = 0.029), respectively. CONCLUSION Despite heterogeneity in endpoints, extent of CAD as quantified by SIS on coronary CTA is a strong, independent predictor of cardiovascular events.
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Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk Women: A Meta-analysis.
Kavousi, M, Desai, CS, Ayers, C, Blumenthal, RS, Budoff, MJ, Mahabadi, AA, Ikram, MA, van der Lugt, A, Hofman, A, Erbel, R, et al
JAMA. 2016;(20):2126-2134
Abstract
IMPORTANCE The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear. OBJECTIVE To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women. DESIGN, SETTING, AND PARTICIPANTS Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies. EXPOSURES CAC score by computed tomography. MAIN OUTCOMES AND MEASURES Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated. RESULTS Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC >0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 [95% CI, 2.02-3.83]; multivariable-adjusted hazard ratio, 2.04 [95% CI, 1.44-2.90]). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction. CONCLUSIONS AND RELEVANCE Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy.
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Prognostic Value of Coronary Artery Calcium Score in Acute Chest Pain Patients Without Known Coronary Artery Disease: Systematic Review and Meta-analysis.
Chaikriangkrai, K, Palamaner Subash Shantha, G, Jhun, HY, Ungprasert, P, Sigurdsson, G, Nabi, F, Mahmarian, JJ, Chang, SM
Annals of emergency medicine. 2016;(6):659-670
Abstract
STUDY OBJECTIVE Coronary artery calcium score (CACS) is a well-established test for risk stratifying asymptomatic patients. Recent studies also indicate that CACS may accurately risk stratify stable patients presenting to the emergency department (ED) with acute chest pain; however, many were underpowered. The purpose of this systematic review and meta-analysis is to evaluate the prognostic value and accuracy of a zero (normal) CACS for identifying patients at acceptable low risk for future cardiovascular events who might be safely discharged home from the ED. METHODS We searched multiple databases for longitudinal studies of CACS in symptomatic patients without known coronary artery disease that reported major adverse cardiovascular events (MACEs), including death and myocardial infarction. Pooled risk ratios, sensitivity, specificity, and likelihood ratios were analyzed. RESULTS Eight studies evaluated 3,556 patients, with a median follow-up of 10.5 months. Pooled prevalence of zero CACS was 60%. Patients with CACS=0 had a significantly lower risk of cardiovascular events compared with those with CACS greater than 0 (MACEs: relative risk 0.06, 95% confidence interval 0.04 to 0.11, I2=0%; death/myocardial infarction: relative risk 0.19; 95% confidence interval 0.08 to 0.47, I2=0%). The pooled event rates for CACS=0 (MACEs 0.8%/year; death/myocardial infarction 0.5%/year) were significantly lower than for CACS greater than 0 (MACEs 14.6%/year; death/myocardial infarction 3.5%/year). Analysis of summary testing parameters showed a sensitivity of 96%, specificity of 60%, positive likelihood ratio of 2.36, and negative likelihood ratio of 0.07. CONCLUSION Acute chest pain patients without history of coronary artery disease, ischemic ECG changes, or increased cardiac enzyme levels commonly have a CACS of zero, with a very low subsequent risk of MACEs or death or myocardial infarction. This meta-analysis proffers the potential role of initial CACS testing for avoiding unnecessary hospitalization and further cardiac testing in acute chest pain patients with a CACS of zero.
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Meta-analysis comparing the effects of rosuvastatin versus atorvastatin on regression of coronary atherosclerotic plaques.
Qian, C, Wei, B, Ding, J, Wu, H, Cai, X, Li, B, Wang, Y
The American journal of cardiology. 2015;(10):1521-6
Abstract
Rosuvastatin and atorvastatin both are high-intensity statins. However, which statin is more effective for the reversion of coronary atherosclerotic plaques remains inconclusive. We, therefore, conducted a meta-analysis to provide further evidence for proper statin selection. Pubmed, The Cochrane Library, Embase, Chinese BioMedicine, and China National Knowledge Infrastructure databases were systematically searched for eligible publications. We also manually reviewed the references from all relevant literature for more trials. Only studies that met our predefined inclusion criteria up to March 31, 2015, were enrolled. Five randomized controlled trials, 4 published in English and 1 in Chinese, were finally included in our study with a total of 1,556 participants, of whom 772 were in the rosuvastatin group and 784 in the atorvastatin group. The dose ratios of rosuvastatin versus atorvastatin were 1:2 in all included trials. Pooling across the studies demonstrated that compared with atorvastatin, rosuvastatin administration further reduced the total atheroma volume (weighted mean difference [WMD] -1.61 mm(3), 95% confidence interval [CI] -2.70 to -0.52; p = 0.004) and percent atheroma volume (WMD -0.34%, 95% CI -0.64 to -0.03; p = 0.03) and improved the lumen volume more significantly (WMD 2.10 mm(3), 95% CI 0.04 to 4.17; p = 0.046). The comparative regression of plaques was not different across subgroups. In conclusion, rosuvastatin is superior to atorvastatin in the reversion of coronary atherosclerotic plaques.
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New Conclusions Regarding Comparison of Sevelamer and Calcium-Based Phosphate Binders in Coronary-Artery Calcification for Dialysis Patients: A Meta-Analysis of Randomized Controlled Trials.
Wang, C, Liu, X, Zhou, Y, Li, S, Chen, Y, Wang, Y, Lou, T
PloS one. 2015;(7):e0133938
Abstract
BACKGROUND Sevelamer hydrochloride is used widely, but its impact upon cardiovascular calcification, cardiovascular mortality, all-cause mortality and hospitalization is not known. OUTCOMES Primary outcome was cardiovascular calcification (coronary artery calcification scores (CACS) and aortic calcification scores (ACS)). Secondary outcomes were serum characteristics, hospitalization, cardiovascular mortality and all-cause mortality. Risk ratio (RR), mean differences and standard mean difference with 95% confidence intervals (CIs) were pooled using random- or fixed-effects models. RESULTS We identified 31 studies (on 23 randomized controlled trials with 4395 participants). An analysis pooling showed a significant decrease in serum levels of phosphate with calcium-based phosphate binders (CBPBs) by 0.17 mg/dL [mean difference (MD), 95% CI, 0.03, 0.31] than sevelamer. A significant difference in the change of CACS by -102.66 [MD: 95% CI, -159.51, -45.80] and ACS by -1008.73 [MD, 95% CI, -1664.75, -352.72] between sevelamer and CBPBs was observed. Prevalence of hypercalcemia (serum levels of calcium >10.2-10.5 mg/dL and >11.0 mg/dL) was significantly smaller for sevelamer (RR = 0.44, 95% CI, 0.33, 0.58; RR = 0.24, 95% CI, 0.14, 0.40). No significant difference was found in hospitalization, all-cause mortality or cardiovascular mortality. CONCLUSIONS This meta-analysis suggests that sevelamer benefits dialysis patients in terms of CACS, ACS and hypercalcemia.