Alternatively, it is plausible that environmental factors such as air particulate matter and heavy metal exposure levels or other unknown factors may have changed and may be contributing to atherosclerotic events in individuals without SMuRFs.26, 27, 28 A major goal of these analyses was to investigate the outcomes of SMuRF\less STEMI patients compared with their counterparts whose myocardial infarctions were more easily explained by traditional risk factors. as well as outcomes. The primary outcome was in\hospital mortality, and the secondary outcome was major adverse cardiovascular events (death, myocardial infarction, or heart failure, during the index admission). Multivariate regression models were used to identify predictors of major adverse cardiovascular events. Of STEMI patients without a prior history of cardiovascular disease 19% also had no history of SMuRFs. This proportion increased from 14% to 23% during the study period (Value /th /thead SMuRFs 0 SMuRFs1.27 (0.72, 2.26)0.4070 SMuRFSRefKillip class22.8 (1.58, 4.97)0.01338.42 (2.71, 26.18)42.59 (0.57, 11.8)1RefCardiac arrest on admissionYes0.35 (0.13, 0.94)0.019NoRefIndex ST deviationYes0.79 (0.27, 2.31)0.696NoRefPositive cardiac biomarkersYes0.21 (0.07, 0.61)0.095NoRefPrehospital aspirinYes1.25 (0.77, 2.05)0.388NoRefHospital transferYes0.82 (0.53, 1.28)0.371NoRefAge group, y 500.29 (0.17, 0.51)0.01050 to 590.22 (0.12, 0.42)60 to 690.41 (0.23, 0.74)70+RefHeart rate group, bpm 650.54 (0.31, 0.94)0.09465 to 740.37 (0.17, 0.83)75 to 890.68 (0.38, 1.22)90+RefSystolic blood pressure group, mm?Hg 1201.18 (0.68, 2.05)0.798120 to 1341.12 (0.56, 2.23)135 to 1540.89 (0.5, 1.59)155+RefSerum creatinine at admission, mmol/L 700.59 (0.35, 1)0.03370 to 840.54 (0.37, 0.78)85 to 990.42 (0.25, 0.69)100+Ref Open in a separate window MACE 7-Epi-docetaxel indicates major adverse cardiovascular events (death/myocardial infarction/heart failure/shock); SMuRFs, standard modifiable cardiovascular risk factors. Discussion This large, multicenter study highlights the importance of the often\overlooked subgroup of STEMI patients with atherosclerosis not predicted by SMuRFs. We validate our previous published findings, from a single\center study, that the proportion of SMuRF\less STEMI patients is not insubstantial and has been significantly increasing in recent years. The relevance of this underappreciated group of STEMI patients is further highlighted by the observed higher in\hospital mortality in this group. The substantial proportion with no SMuRFs at the time of their index event is consistent with previously published studies at 18% overall12, 15, 16, 17 and represents a significant burden of CVD at a national and global scale, with an estimated 7.3?million acute myocardial infarctions per year worldwide.5. The STEMIs in the SMuRF\less group were not explained by obesity, family history of premature coronary artery disease, or age (with body mass index being less in the SMuRF\less group than the explained STEMI group, similar rates of relevant family history, and similar ages). It is interesting to observe that the proportion of SMuRF\less STEMI patients was a third higher in men than women. The YOUNG\MI registry similarly found that 17% of ACS patients aged less than 50?years old presenting with a type 1 acute myocardial infarction had no SMuRFs and in addition found that fewer than 50% of patients in their cohort would have met the criteria for primary prevention statin therapy according to current American guidelines.17 Although it is essential that we continue at a community and primary healthcare level to identify and address the burden of known risk factors for atherosclerosis, parallel efforts should continue toward unraveling the biological mechanisms underlying disease in SMuRF\less individuals. New technologies and data science advances in omics and multiomics approaches will allow novel discovery approaches to be adopted in accurately phenotyped cohorts with the potential to identify as yet unknown biological networks and processes.18 Polygenic risk scores have been developed that can stratify an individual’s risk largely independent of the individual’s SMuRFs and can improve risk prediction over traditional risk factorCderived scores.19 Future cohort studies such as GRACE and CONCORDANCE registries would benefit from building biobanks into their study design to enable validation of these scores as well as identification of new biomarkers. The ultimate marker of risk for myocardial infarction is a noninvasive measure of early atherosclerotic disease itself, integrating not just the attacking risk factors but also the host response.18 Currently, in clinical practice, cardiac computed tomographyboth coronary calcium score and coronary angiographyare all that we have available. Research tools measuring early vascular dysfunction or disease include carotid intimal medial thickness and brachial artery reactivity.20, 21 But there is an absence of circulating blood markers of atherosclerosis activity, with the nonspecific inflammatory marker high\sensitive C\reactive protein being the closest clinically available measure that we have. Application of noninvasive imaging of subclinical vascular disease supports the importance of the problem. One recent study demonstrated evidence of atherosclerosis in 50% of adults without SMuRFs.21 Another study showed that in asymptomatic adults with no SMuRFs, 32% had evidence of coronary artery calcification, and 12% had moderate or severe coronary artery calcification, defined as a coronary artery calcium score greater than 100 Agatston units.22 Currently, international guidelines do not recommend screening with coronary artery calcium or computed tomographic coronary angiography in patients deemed at low risk based on traditional risk factor scores.23, 24, 25 Data highlighting the burden of disease in the SMuRF\less population and the dramatic difference earlier detection and targeted prevention would make suggest the need for.This study uses 2 sequential large, multicenter registries to examine the proportion and outcomes of SMuRF\less ST\segmentCelevation myocardial infarction (STEMI) patients. Methods and Results We identified 3081 STEMI patients without a prior history of cardiovascular disease in the Australian GRACE (Global Registry of Acute Coronary Events) and CONCORDANCE (Cooperative National Registry of Acute Coronary Syndrome Care) registries, encompassing 42 hospitals, between 1999 and 2017. as well as outcomes. The primary outcome was in\hospital mortality, and the secondary outcome was major adverse cardiovascular events (death, myocardial infarction, or heart failure, during the index admission). Multivariate regression models were used to identify predictors of major adverse cardiovascular events. Of STEMI patients without a prior history of cardiovascular disease 19% also had no history 7-Epi-docetaxel of SMuRFs. This proportion increased from 14% to 23% during the study period (Value /th /thead SMuRFs 0 SMuRFs1.27 (0.72, 2.26)0.4070 SMuRFSRefKillip class22.8 (1.58, 4.97)0.01338.42 (2.71, 26.18)42.59 (0.57, 11.8)1RefCardiac arrest on admissionYes0.35 (0.13, 0.94)0.019NoRefIndex ST deviationYes0.79 (0.27, 2.31)0.696NoRefPositive cardiac biomarkersYes0.21 (0.07, 0.61)0.095NoRefPrehospital aspirinYes1.25 (0.77, 2.05)0.388NoRefHospital transferYes0.82 (0.53, 1.28)0.371NoRefAge group, y 500.29 (0.17, 0.51)0.01050 to 590.22 (0.12, 0.42)60 to 690.41 (0.23, 0.74)70+RefHeart rate group, bpm 650.54 (0.31, 0.94)0.09465 to 740.37 (0.17, 0.83)75 to 890.68 (0.38, 1.22)90+RefSystolic blood pressure group, mm?Hg 1201.18 (0.68, 2.05)0.798120 to 1341.12 (0.56, 2.23)135 to 1540.89 (0.5, 1.59)155+RefSerum creatinine at admission, mmol/L 700.59 (0.35, 1)0.03370 to 840.54 (0.37, 0.78)85 to 990.42 (0.25, 0.69)100+Ref Open in a separate window MACE indicates major adverse cardiovascular events (death/myocardial infarction/heart failure/shock); SMuRFs, standard modifiable cardiovascular risk factors. Discussion This large, multicenter study highlights the importance of the often\overlooked subgroup of STEMI patients with atherosclerosis not predicted by SMuRFs. We validate our previous published findings, from a single\center study, that the proportion of SMuRF\less STEMI patients is not insubstantial and has been significantly increasing in recent years. The relevance of this underappreciated group of STEMI patients is further highlighted by the observed higher in\hospital mortality in this group. The substantial proportion with no SMuRFs at the time of their index event is consistent with previously published studies at 18% overall12, 15, 16, 17 and represents a significant burden of CVD at a national and global scale, with an estimated 7.3?million acute myocardial infarctions per year worldwide.5. The STEMIs in the SMuRF\less group were not explained by obesity, family history of premature coronary artery disease, or age (with body mass index being less in the SMuRF\less group than the explained STEMI group, similar rates of relevant family history, and similar ages). It is interesting to observe that the proportion of SMuRF\less STEMI individuals was a third higher in males than ladies. The Adolescent\MI registry similarly found that 17% of 7-Epi-docetaxel ACS individuals aged less than 50?years old presenting with a type 1 acute myocardial infarction had no SMuRFs and in addition found that fewer than 50% of individuals in their cohort would have met the criteria for Lactate dehydrogenase antibody primary prevention statin therapy according to current American recommendations.17 Although it is essential that we continue at a community and main healthcare level to identify and address the burden of known risk factors for atherosclerosis, parallel attempts should continue toward unraveling the biological mechanisms underlying disease in SMuRF\less individuals. New systems and data technology improvements in omics and multiomics methods will allow novel discovery approaches to become used in accurately phenotyped cohorts with the potential to identify as yet unfamiliar biological networks and processes.18 Polygenic risk scores have been developed that can stratify an individual’s risk largely independent of the individual’s SMuRFs and 7-Epi-docetaxel may improve risk prediction over traditional risk factorCderived scores.19 Long term cohort studies such as GRACE and CONCORDANCE registries would benefit from building biobanks into their study design to enable validation of these scores as well as identification of new biomarkers. The ultimate marker of risk for myocardial infarction is definitely a noninvasive measure of early atherosclerotic disease itself, integrating not just the attacking risk factors but also the sponsor response.18 Currently, in clinical practice, cardiac computed tomographyboth coronary calcium score and coronary angiographyare all that we have available. Study tools measuring early vascular dysfunction.
