Standard Cardiovascular Risk Factors Research Articles

In-Hospital Mortality and Treatment in Patients With Acute Coronary Syndrome With and Without Standard Modifiable Cardiovascular Risk Factors: Findings From the CCC-ACS Project.

Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline-directed medical therapy for these patients. In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in-hospital all-cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF-less). SMuRF-less patients had higher in-hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19-1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in-hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07-1.70]). Guideline-directed optimal medical therapy (receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58-1.67]) in SMuRF-less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66-0.98]). Sensitivity analyses were consistent with these results. SMuRF-less patients were associated with an increased risk of in-hospital mortality. Guideline-directed medical therapy was less effective in SMuRF-less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF-less patients. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.

Prognostic significance of triglyceride-glucose index in acute coronary syndrome patients without standard modifiable cardiovascular risk factors

BackgroundA significant percentage of patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) are being identified. Nonetheless, the prognostic influence of the TyG index on adverse events in this type of patient remains unexplored. The aim of this study was to assess the prognostic value of the TyG index among ACS patients without SMuRFs for predicting adverse outcomes.MethodsThis study involved 1140 consecutive patients who were diagnosed with ACS without SMuRFs at Beijing Anzhen Hospital between May 2018 and December 2020 and underwent coronary angiography. Each patient was followed up for a period of 35 to 66 months after discharge. The objective of this study was to examine major adverse cardiac and cerebrovascular events (MACCE), which included all-cause mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, as well as ischemia-driven revascularization.ResultsDuring the median follow-up period of 48.3 months, 220 (19.3%) MACCE events occurred. The average age of the participants was 59.55 ± 10.98 years, and the average TyG index was 8.67 ± 0.53. In the fully adjusted model, when considering the TyG index as either a continuous/categorical variable, significant associations with adverse outcomes were observed. Specifically, for each 1 standard deviation increase in the TyG index within the highest TyG index group, there was a hazard ratio (HR) of 1.245 (95% confidence interval CI 1.030, 1.504) for MACCE and 1.303 (95% CI 1.026, 1.653) for ischemia-driven revascularization (both P < 0.05), when the TyG index was analyzed as a continuous variable. Similarly, when the TyG index was examined as a categorical variable, the HR (95% CI) for MACCE in the highest TyG index group was 1.693 (95% CI 1.051, 2.727) (P < 0.05) in the fully adjusted model, while the HR (95% CI) for ischemia-driven revascularization was 1.855 (95% CI 0.998, 3.449) (P = 0.051). Additionally, the TyG index was found to be associated with a poor prognosis among the subgroup.ConclusionThe TyG index is correlated with poor prognosis in patients with ACS without SMuRFs, suggesting that it may be an independent predictive factor of adverse events among these individuals.

Improving clinical outcomes for patients with coronary artery disease despite no standard modifiable cardiovascular risk factors (SMuRF): not out of the woods yet.

Improving clinical outcomes for patients with coronary artery disease despite no standard modifiable cardiovascular risk factors (SMuRF): not out of the woods yet.

No standard modifiable cardiovascular risk factors in acute myocardial infarction: prevalence, pathophysiology, and prognosis.

Standard modifiable cardiovascular risk factors (SMuRFs), such as hypertension, diabetes, dyslipidemia, and current smoking, are associated with the development of atherosclerotic cardiovascular diseases including acute myocardial infarction (MI). Thus, therapeutic approaches against SMuRFs are important as primary and secondary prevention of cardiovascular diseases. In patients with acute MI, however, the prognosis is counterintuitively poor when SMuRFs are lacking. The growing evidence has explored the prevalence, pathophysiology, and prognosis of SMuRF-less patients in acute MI and suggested the potential underlying mechanisms. This review article summarizes the clinical evidence and relevance of the lack of SMuRFs in acute MI.

Cardiovascular Risk in Cancer Patients Treated with Immune Checkpoint Inhibitors: Challenges and Future Directions.

Cardiovascular disease is the leading cause of non-cancer related mortality and morbidity among people living with or cured from cancer. Immune checkpoint inhibitors (ICIs) are systemic anti-cancer therapies that have revolutionised the treatment of numerous cancers, even achieving durable long-term responses among patients with metastatic disease. However, the pro-inflammatory effects of ICIs have been postulated to increase the risk of atherosclerotic cardiovascular disease (ASCVD) in cancer survivorship. Standard modifiable cardiovascular risk factors can further contribute to ASCVD risk during cancer survivorship but are not routinely screened and are often untreated in patients with cancer. With the expanding use of ICIs leading to improved cancer survivorship, cardiovascular risk identification and prevention will be paramount in the care of patients with cancer. This review highlights the practical challenges associated with ASCVD prevention among the growing number of patients treated with ICIs for cancer, including balancing competing mortality risks from cancer and ASCVD, the lack of ICI-specific cardiovascular risk stratification tools, potential interactions between cardiovascular and oncological therapies, and barriers to implementation of cardiovascular screening and prevention within existing healthcare systems.

Aortic Valve Stenosis Causes Accumulation of Extracellular Hemoglobin and Systemic Endothelial Dysfunction.

Whether aortic valve stenosis (AS) can adversely affect systemic endothelial function independently of standard modifiable cardiovascular risk factors is unknown. We therefore investigated endothelial and cardiac function in an experimental model of AS mice devoid of standard modifiable cardiovascular risk factors and human cohorts with AS scheduled for transcatheter aortic valve replacement. Endothelial function was determined by flow-mediated dilation using ultrasound. Extracellular hemoglobin (eHb) concentrations and nitric oxide (NO) consumption were determined in blood plasma of mice and humans by ELISA and chemiluminescence. This was complemented by measurements of aortic blood flow using 4-dimensional flow acquisition by magnetic resonance imaging and computational fluid dynamics simulations. The effects of plasma and red blood cell (RBC) suspensions on vascular function were determined in transfer experiments in a murine vasorelaxation bioassay system. In mice, the induction of AS caused systemic endothelial dysfunction. In the presence of normal systolic left ventricular function and mild hypertrophy, the increase in the transvalvular gradient was associated with elevated eryptosis, increased eHb, and increased plasma NO consumption; eHb sequestration by haptoglobin restored endothelial function. Because the aortic valve orifice area in patients with AS decreased, postvalvular mechanical stress in the central ascending aorta increased. This was associated with elevated eHb, circulating RBC-derived microvesicles, eryptotic cells, lower haptoglobin levels without clinically relevant anemia, and consecutive endothelial dysfunction. Transfer experiments demonstrated that reduction of eHb by treatment with haptoglobin or elimination of fluid dynamic stress by transcatheter aortic valve replacement restored endothelial function. In patients with AS and subclinical RBC fragmentation, the remaining circulating RBCs before and after transcatheter aortic valve replacement exhibited intact membrane function, deformability, and resistance to osmotic and hypoxic stress. AS increases postvalvular swirling blood flow in the central ascending aorta, triggering RBC fragmentation with the accumulation of hemoglobin in the plasma. This increases NO consumption in blood, thereby limiting vascular NO bioavailability. Thus, AS itself promotes systemic endothelial dysfunction independent of other established risk factors. Transcatheter aortic valve replacement is capable of limiting NO scavenging and rescuing endothelial function by realigning postvalvular blood flow to near physiological patterns. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05603520 and NCT01805739.

Arterial structure and function in children with inflammatory bowel disease.

People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic low-grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk. We performed a case-control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima-media thickness. High-sensitivity C-reactive protein and fasting lipids were measured. We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z-score, blood pressure, and low-density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis. We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes.

Impact of Cancer, Inflammation, and No Standard Risk Factors in Patients With Myocardial Infarction

BackgroundThe lack of standard modifiable cardiovascular risk factors (SMuRFs), including hypertension, diabetes, dyslipidemia, and smoking, is reportedly associated with poor outcomes in acute myocardial infarction (AMI). Among patients with no SMuRFs, cancer and chronic systemic inflammatory diseases (CSIDs) may be major etiologies of AMI. ObjectivesThe purpose of this study was to evaluate clinical characteristics and outcomes of patients with cancer, CSIDs, and no SMuRFs in AMI. MethodsThis multicenter registry included 2,480 patients with AMI undergoing percutaneous coronary intervention. Patients were divided into 4 groups: active cancer, CSIDs, no SMuRFs, and those remaining. The coprimary endpoint was major adverse cardiovascular events (MACE) and major bleeding events, during hospitalization and after discharge. ResultsOf 2,480 patients, 104 (4.2%), 94 (3.8%), and 120 (4.8%) were grouped as cancer, CSIDs, and no SMuRFs, respectively. During the hospitalization, MACE rates were highest in the no SMuRFs group, followed by the cancer, CSIDs, and SMuRFs groups (22.5% vs 15.4% vs 12.8% vs 10.2%; P < 0.001), whereas bleeding risks were highest in the cancer group, followed by the no SMuRFs, CSIDs, and SMuRFs groups (15.4% vs 10.8% vs 7.5% vs 4.9%; P < 0.001). After discharge, the rates of MACE (33.3% vs 22.7% vs 11.3% vs 9.2%; P < 0.001) and bleeding events (8.6% vs 6.7% vs 3.8% vs 2.9%; P = 0.01) were higher in the cancer group than in the CSIDs, no SMuRFs, and SMuRFs groups. ConclusionsPatients with active cancer, CSIDs, and no SMuRFs differently had worse outcomes after AMI in ischemic and bleeding endpoints during hospitalization and/or after discharge, compared with those with SMuRFs.

Chronic coronary syndromes without standard modifiable cardiovascular risk factors and outcomes: the CLARIFY registry.

It has been reported that patients without standard modifiable cardiovascular (CV) risk factors (SMuRFs-diabetes, dyslipidaemia, hypertension, and smoking) presenting with first myocardial infarction (MI), especially women, have a higher in-hospital mortality than patients with risk factors, and possibly a lower long-term risk provided they survive the post-infarct period. This study aims to explore the long-term outcomes of SMuRF-less patients with stable coronary artery disease (CAD). CLARIFY is an observational cohort of 32 703 outpatients with stable CAD enrolled between 2009 and 2010 in 45 countries. The baseline characteristics and clinical outcomes of patients with and without SMuRFs were compared. The primary outcome was a composite of 5-year CV death or non-fatal MI. Secondary outcomes were 5-year all-cause mortality and major adverse cardiovascular events (MACE-CV death, non-fatal MI, or non-fatal stroke). Among 22 132 patients with complete risk factor and outcome information, 977 (4.4%) were SMuRF-less. Age, sex, and time since CAD diagnosis were similar across groups. SMuRF-less patients had a lower 5-year rate of CV death or non-fatal MI (5.43% [95% CI 4.08-7.19] vs. 7.68% [95% CI 7.30-8.08], P = 0.012), all-cause mortality, and MACE. Similar results were found after adjustments. Clinical event rates increased steadily with the number of SMuRFs. The benefit of SMuRF-less status was particularly pronounced in women. SMuRF-less patients with stable CAD have a substantial but significantly lower 5-year rate of CV death or non-fatal MI than patients with risk factors. The risk of CV outcomes increases steadily with the number of risk factors.

Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.

Pattern of atherosclerotic plaque and type of MI in the patients of cardiovascular disease with and without standard modifiable cardiovascular risk factors (SMuRF)

Pattern of atherosclerotic plaque and type of MI in the patients of cardiovascular disease with and without standard modifiable cardiovascular risk factors (SMuRF)

Myocardial dysfunction in patients with rheumatoid arthritis in the speckle-tracking echocardiography and its relationship with the clinical characteristics of the disease

patients with RA have an approximately 50% increased risk of cardiovascular events and cardiovascular death. Cardiovascular diseases lead to a decrease in life expectancy, and the determination of the mechanisms of myocardial damage in patients with RA is of great importance for the development of methods for the early prevention of heart failure. The aim of our study was to study myocardial dysfunction using speckle tracking echocardiography (STE) in patients with RA and to find out possible correlations with the course of the disease and risk factors for cardiovascular diseases. Materials and methods. 29 RA patients were examined (5 in remission, 17.2%). Rheumatoid factor (RF), the level of antibodies to cyclic citrullinated peptides (a-CRP), quantitative C-reactive protein (CRP) was determined in the blood of all patients, and echocardiography and speckle-tracking echocardiography were performed to determine indicators of longitudinal deformation of the left ventricle. Disease activity was determined using the DAS28 index (CRP) and other functional and laboratory indicators. The results. The study of STE indicators is much better than "classical" echocardiography, revealing latent preclinical heart lesions. We established a significant decrease in Global Longitudinal Strain in the basal anterior and basal antero-septal segments (-17.24±3.01% and 15.94±9.37%, respectively) and preservation of local strain in the apical and middle segments (respectively -26.95+4.95% and -21.69+3.05%). In general, 41.2% of patients with RA had lesions of the basal segments. When analyzing the correlation between disease activity and deformation in STE, an inverse relationship between the DAS28 index and apical deformation (API Strain) was established (r=-0.50, р=0.06). The highest correlations were found between STE and functional status of disease: HAQ-DI score (r=-0.51, p=0.05) and VAS activity (r=-0.64, p=0.01). Conclusions. Functional activity according to the HAQ-DI score and VAS had a significantly greater relationship with preclinical manifestations of heart damage (detected by STE) than standard cardio-vascular risk factors. It is necessary to continue the search for other important factors that can lead to the formation of heart lesions and are related to both the activity of the disease and the functional status of patients. It is expedient to conduct comparative studies of STE in RA and coronary artery disease to clarify the differences in the processes of formation of myocardial damage.

Impact of the number of modifiable risk factors on clinical outcomes after percutaneous coronary intervention: An analysis from the e-Ultimaster registry

AimsA substantial proportion of the patients undergoing percutaneous coronary intervention (PCI) have none of the of standard modifiable cardiovascular risk factors (SMuRFs): hypertension, diabetes, hypercholesterolaemia and smoking. The aim of this analysis was to compare clinical outcomes after PCI according to the number of SMuRFs. MethodsPatients with an indication for a PCI were stratified based upon the number of SMuRFs: 0, 1, 2 or 3–4. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction or clinically driven target lesion revascularization at 1-year. Inverse weighted propensity score (IWPS) adjustment was performed to adjust for differences in baseline characteristics. ResultsThe prevalence of SMuRFs was: 0 SMuRF 16.4 %; 1 SMuRF 27.8 %; 2 SMuRFs 34.7 % and 3–4 SMuRFs 21.1 %. Patients without SMuRFs were younger, more likely to be male and had less complex coronary artery disease. The incidence of TLF increased with the number of SMuRFs: 2.65 %, 2.75 %, 3.23 %, and 4.24 %, Ptrend < 0.001. The relative risk (RR) for a TLF was 60 % higher (95 % confidence interval 1.32–1.93, p < 0.01) for patients with 3–4 SMuRFs compared to patients without SMuRFs. The trend remained (Ptrend < 0.01) after IWPS with TLF rates of 2.88 %, 2.64 %, 2.88 % and 3.65 %. The RR for a TLF was 27 % higher (95 % CI 1.05–1.53, p < 0.01). ConclusionThe incidence of clinical events at 1-year increased with the number of SMuRFs. While patients without SMuRFs have a relatively favourable risk profile, more research is needed to optimize therapeutic management in the majority of patients.

Mortality of patients presented with acute ST-segment elevation myocardial infarction according to the status of standard modifiable cardiovascular risk factors

BackgroundStandard modifiable cardiovascular risk factors (SMuRFs) remain well-established elements of assessing cardiovascular risk scores. However, there is growing evidence that patients presented without known SMuRFs at admission demonstrate worse post-myocardial outcomes. The aim of the study was to assess the influence of the SMuRF status on short- and long-term mortality rates in patients with first-time ST-segment elevation myocardial infarction (STEMI). MethodsThis observational, cross-sectional study covered 182,726 patients admitted between 2003–2020 to the CathLabs, according to data from the Polish Registry of Acute Coronary Syndrome. Both baseline characteristics and mortality (in-hospital, 30-day, and 12-month) were examined and stratified by SMuRF status. The predictors of mortality were assessed at selected time points by multivariable analysis. ResultsThe majority of STEMI patients had at least one SMuRF (88.7%), however, mortality rates of SMuRF-less individuals were greater at selected time points of the follow-up (p < 0.001), and persisted at a higher level during each year of the follow-up period compared to the SMuRF group and general population. Furthermore, the SMuRFs status constituted an independent predictor of mortality at the 30-day (OR: 1.345; 95% CI: 1.142–1.585, p < 0.001) and 12-month (OR: 1.174; 95% CI: 1.054–1.308, p < 0.001) follow-ups. ConclusionsSMuRF-less individuals presented with STEMI are at an increased risk of all-cause mortality compared to those with at least one SMuRF. Consequently, further investigations regarding the recognition and treatment of risk factors, irrespective of SMuRF status, are indicated.

In-hospital and 1-year outcomes of patients without modifiable risk factors presenting with acute coronary syndrome undergoing PCI: a Sex-stratified analysis.

A considerable proportion of patients admitted with acute coronary syndrome (ACS) have no standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking). The outcomes of this population following percutaneous coronary intervention (PCI) are debated. Further, sex differences within this population have yet to be established. This retrospective cohort study included 7,847 patients with ACS who underwent PCI. The study outcomes were in-hospital mortality, all-cause mortality, and major adverse cardio-cerebrovascular events (MACCE). The association between the absence of SMuRFs (SMuRF-less status) and outcomes among all the patients and each sex was assessed using logistic and Cox proportional hazard regressions. Approximately 11% of the study population had none of the SMuRFs. During 12.13 [11.99-12.36] months of follow-up, in-hospital mortality (adjusted-odds ratio (OR):1.51, 95%confidence interval (CI): 0.91-2.65, P:0.108), all-cause mortality [adjusted-hazard ratio (HR): 1.01, 95%CI: 0.88-1.46, P: 0.731], and MACCE (adjusted-HR: 0.93, 95%CI:0.81-1.12, P: 0.412) did not differ between patients with and without SMuRFs. Sex-stratified analyses recapitulated similar outcomes between SMuRF+ and SMuRF-less men. In contrast, SMuRF-less women had significantly higher in-hospital (adjusted-OR: 3.28, 95%CI: 1.92-6.21, P < 0.001) and all-cause mortality (adjusted-HR:1.41, 95%CI: 1.02-3.21, P: 0.008) than SMuRF+ women. Almost one in 10 patients with ACS who underwent PCI had no SMuRFs. The absence of SMuRFs did not confer any benefit in terms of in-hospital mortality, one-year mortality, and MACCE. Even worse, SMuRF-less women paradoxically had an excessive risk of in-hospital and one-year mortality.

Characteristics, Treatment, and In-Hospital Outcomes of Older Patients With STEMI Without Standard Modifiable Risk Factors

BackgroundStrategies targeting standard modifiable cardiovascular risk factors (SMuRFs), including hypertension, diabetes, hypercholesterolemia, and smoking, have been well established to prevent coronary heart disease. However, few studies have evaluated the management and outcomes of older patients without SMuRFs after myocardial infarction. ObjectivesThe authors sought to evaluate the profile of patients with ST-segment elevation myocardial infarction (STEMI) aged ≥75 years without SMuRFs. MethodsThis study is based on the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project. Patients aged ≥75 years with a first presentation of STEMI were enrolled in this study between November 2014 and December 2019. Modified Poisson regression was used to evaluate the association between SMuRF-less and in-hospital outcomes. ResultsAmong 10,775 patients with STEMI aged ≥75 years, 1,633 (15.16%) had no SMuRFs. Compared with those with SMuRF, SMuRF-less patients received less evidence-based treatment. In-hospital mortality was similar among patients with and without SMuRFs (5.44% vs 5.14%; P = 0.630). However, after adjustment for patient characteristics and treatment, being SMuRF-less was significantly associated with a reduced risk of mortality (RR: 0.80; 95% CI: 0.65-0.99; P = 0.043). SMuRF-less patients also had a significantly reduced risk of in-hospital death when only adjusting for in-hospital treatment (RR: 0.78; 95% CI: 0.63–0.98; P = 0.030), regardless of patient characteristics. ConclusionsApproximately 1 in 7 STEMI patients in China ≥75 years old had no SMuRFs. The similar mortality in patients with and without SMuRF can be partially explained by the inadequate in-hospital treatment of SMuRF-less patients. The quality of care for older patients without SMuRF should be improved. (CCC Project–Acture Coronary Syndrome; NCT02306616)

Differences in left anterior descending coronary artery disease in participants without standard modifiable cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract Background/Introduction The development of coronary artery disease (CAD) and myocardial infarction (MI) in the absence of standard modifiable cardiovascular risk factors (SMuRFs) has been highlighted as an unmet clinical need, accounting for between 10-27% of ST elevation MI and associated with higher 30-day mortality. One potential contributor to the early mortality is the higher observed rates of LAD territory culprit lesions in SMuRFless patients compared to those with at least one SMuRF. Purpose To characterise the differential proportion of LAD disease in an asymptomatic population with no prior cardiovascular disease (CVD) history, comparing individuals with CAD despite no SMuRFs to those with at least one SMuRF in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods A MESA sub-cohort with a baseline coronary artery calcium score (CACS) &amp;gt;0 Agatston units (AU) was prepared. SMuRF status was assigned by self-report, treatment, or biomarkers for hypertension, hypercholesterolaemia, diabetes, and smoking. Proportion of disease in the left main, LAD, circumflex, and right coronary arteries were calculated by the vessel CACS divided by the total CACS. Standard descriptive statistics were used to characterise baseline differences. Group comparisons were completed with Wilcoxon rank sum for continuous measures and Chi-square for categorical. Results A CAC positive cohort of 3,417 participants was prepared from participants with SMuRF and CT imaging data, 14.3% of whom were considered SMuRFless. Total CACS was lower in SMuRFless participants compared to those with ≥1 SMuRF (58 AU vs. 102 AU, p&amp;lt;0.0001). However, proportion of calcium burden in the LAD was significantly higher in SMuRFless participants with CAD (74.2% vs. 56.8%, p&amp;lt;0.0001). When considering clinically significant CACS strata, proportion of LAD calcium burden was not significantly different between SMuRFless vs. ≥1 SMuRF participants with a total CACS of 1-99 AU (93.7% vs. 80.0%). However, statistically significant differences in LAD calcium proportion were observed between SMuRFless vs. ≥1 SMuRF participants with a total CACS 100-400 AU (69.5% vs. 57.8%) and CACS&amp;gt;400AU (45.2% vs. 40.5%). This difference remained significant during multivariate modelling, including consideration of absolute CACS. Conclusion Of patients with evidence of CAD (CACS&amp;gt;0) in the MESA cohort, SMuRFless status was associated with a higher proportion of LAD disease compared to participants with ≥1 SMuRF. This adds to previous observations in STEMI cohorts suggesting a heightened susceptibility to atherosclerosis development in the LAD territory against a lower traditional risk burden, and highlights the need for consideration of distinct biology and clinical significance in future studies.Fig. 1Fig. 2

In-hospital and 1-year outcomes of patients without modifiable risk factors presenting with acute coronary syndrome undergoing PCI: a sex-stratified analysis

Abstract Background The standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking) are known to play a major role in the pathogenesis of coronary heart disease (CHD). Despite endeavors aiming at primary and secondary prevention of these risk factors, CHD has remained a leading cause of mortality and morbidity worldwide. A considerable proportion of patients admitted with acute coronary syndrome (ACS) have no SMuRFs, the outcomes of whom following percutaneous coronary intervention (PCI) are debated. Further, sex differences within this population have yet to be established. Purpose The present study aimed to evaluate the association between SMuRF-less status and post-PCI outcomes among patients with ACS. Further, we sought to determine possible sex differences in the post-PCI outcomes related to the SMuRF-less status. Methods This retrospective cohort study included 7847 patients with ACS who underwent PCI. The study outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACCE). The association between the absence of SMuRFs (SMuRF-less status) and outcomes among all the patients and each sex was assessed using logistic and Cox proportional hazard regressions. A separate landmark analysis with the landmark (cutoff) set at 30 days after the index procedure was performed as well. Models were adjusted for age, sex, body mass index, chronic obstructive pulmonary disease, cerebrovascular accident, previous myocardial infarction, estimated glomerular filtration rate, ejection fraction, and left main disease. Results Approximately 11% of the study population had none of the SMuRFs. The SMuRF-less and SMuRF+ groups aged 63.10 ±8.91 (85.1% males) and 62.53 ± 10.91 years (74.9% males), respectively. During 12.13 [11.99-12.36] months of follow-up, the followings were respective event numbers in the SMuRF-less and SMuRF+ groups: all-cause mortality: 35 (4.1%) and 273 (3.9%); MACCE: 99 (11.6%) and 898 (12.8%). All-cause mortality (adjusted-hazard ratio (HR): 1.01, 95%CI: 0.88-1.46, P: 0.731), and MACCE (adjusted-HR: 0.93, 95%CI:0.81-1.12, P: 0.412) did not differ between patients with and without SMuRFs (Figure 1). Sex-stratified analyses recapitulated similar outcomes between SMuRF+ and SMuRF-less men. In contrast, SMuRF-less women had significantly higher all-cause mortality (adjusted-HR:1.41, 95%CI: 1.02-3.21, P: 0.008) than SMuRF+ women (Figure 1). Notably, following landmark analyses, this significant association among women disappeared (adjusted-HR: 0.99, 95%CI: 0.41-2.59, P:0.991), implying that its significance stemmed, to some extent, from higher 30-day mortality (Figure 1,2). Conclusions Almost one in 10 patients with ACS who underwent PCI had no SMuRFs. The absence of SMuRFs did not confer any benefit in terms of in-hospital mortality, one-year mortality, and MACCE. Even worse, SMuRF-less women paradoxically had an excessive risk of one-year mortality.

Standard modifiable risk factors and mortality in patients with ST-segment elevation myocardial infarction: findings from the FRENCHIE cohort

Abstract Background Improvements in the treatment of the 4 main standard modifiable cardiovascular (CV) risk factors (SMuRFs), hypertension (HTN), diabetes, hypercholesterolemia, and smoking, have led to better survival in patients with acute myocardial infarction (AMI). Recent large observational studies have reported that an increasing and sizable proportion of AMI patients have no SMuRF, and these SMURFless patients have (counterintuitively) worse outcomes than patients with at least one SMuRF. Purpose Using a French nationwide MI registry, we aimed to describe the proportion, characteristics and in-hospital mortality of ST-segment elevation MI (STEMI) patients according to the burden of SMuRFs. Methods The French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing MI cohort, which collects data from all patients hospitalized for AMI &amp;lt; 48 h of symptom onset in 21 french centres. For the present analysis, patients with STEMI and without prior coronary artery disease (CAD) admitted in 2019 and 2020 were studied. SMuRFless patients were compared to patients with 1 SMuRF or ≥2 SMuRFs. Results Among 4692 STEMI patients, 986(21%) were SMuRFless, 2001(43%) had 1 SMuRF, and 1705(36%) had ≥2 SMuRFs . Among patients with SMuRFs, smoking (51.8%) and HTN (51.1%) were the most frequent SMuRF and HTN+hypercholesterolemia (10.3%) and HTN+smoking (8.3%) the most frequent SMuRFs associations. When compared with patients with 1 or ≥ 2 SMuRFs, SMuRFless patients were characterized by older age (64.1 vs 60.2 and 62.8 y, respectively), but lower rate of female sex (21.7 vs 22.2 and 26.2%, respectively), LVEF&amp;lt;40% (24.5 vs 26.7 and 26.2%), and lower admission CRP (14.8±38.3 vs 15.3±38.7 and 17.3±40.1 mg/L, respectively). There was a slight increase in BMI with increasing SMURFs (0 SMURF : 26±3.9 ; 1 SMuRF : 26.3±4.5 ; ≥2 SMuRFs : 28.0±5 kg/m²). As expected, SMuRFless patients were less frequently under chronic CV medications (7.9 vs 23.5 and 57.7%, respectively). However, acute STEMI medications were similar across the 3 groups. Crude in-hospital mortality showed a trend toward an increase with the number of SMuRFs (p = 0.123). By multivariate logistic regression analysis, the number of SMURFs was associated with increasing in-hospital mortality (Figure). In stratified analyses, the odds were similar for both sexes. Conclusion In French patients with an inaugural STEMI, one in 5 patient was SMURFless. The burden of risk factors was independently correlated to worse in-hospital survival. These observations emphasize the importance of standard RF on acute MI outcomes.SMuRF and in-hospital death(forest plot)

Uric Acid Levels, Number of Standard Modifiable Cardiovascular Risk Factors, and Prognosis in Patients With Coronary Artery Disease: A Large Cohort Study in Asia.

Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0-1 versus 2-3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow-up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high-UA-level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197-1.804]) and medium-UA-level group (adjusted HR, 1.478 [95% CI, 1.012-2.160]), compared with the low-UA-level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence-based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.