Risk Of Early Myocardial Infarction Research Articles

Sex Differences in 10-Year Outcomes After Percutaneous Coronary Intervention With Drug-Eluting Stents: Insights From the DECADE Cooperation.

Although some studies have investigated sex-related outcomes up to 5 years after percutaneous coronary intervention (PCI), analyses at longer follow-up (ie, to 10 years) in large cohorts treated exclusively with drug-eluting stent (DES) platforms are lacking. Therefore, this study aimed to define whether sex-related differences in long-term outcomes after PCI persist both in the DES era and at longer-term follow-up. Individual data of patients treated with DES in 5 randomized controlled trials with 10-year follow-up were pooled. Patients were divided into 2 groups by sex. The analysis of individual participant data was performed using a 1-stage approach by entering a clustering effect by parent study in all univariable and multivariable models focusing on sex. The main outcomes of interest for this analysis included cardiovascular death, myocardial infarction, repeat revascularization, and definite stent thrombosis to 10 years after PCI. Survival was analyzed by the Kaplan-Meier method to estimate the time to first event, and differences between the 2 groups were tested with the log-rank test. Hazard ratios (HRs) and 95% CIs were calculated with a Cox proportional hazards model. Conventional multivariable analyses with adjustment for relevant variables were performed. Among 9700 patients undergoing PCI with DES implantation included in the present analysis, 2296 were women and 7404 were men. Through to 10 years, cardiovascular death occurred in 407 of the 2296 female patients and 1012 of the 7404 male patients (adjusted HR [HRadj], 0.94 [95% CI, 0.80-1.11]). Female sex was associated with a lower risk of repeat revascularization of the target lesion (HRadj, 0.80 [95% CI, 0.74-0.87]), target vessel (HRadj, 0.81 [95% CI, 0.76-0.87]), and nontarget vessels (HRadj, 0.69 [95% CI, 0.62-0.77]). Compared with male patients, female patients displayed an increased risk of myocardial infarction in the first 30 days after PCI with DES (HRadj, 1.65 [95% CI, 1.24-2.19]) but a comparable risk of myocardial infarction thereafter. The risk of definite stent thrombosis was not significantly different between female and male patients (HRadj, 1.14 [95% CI, 0.89-1.47]). Through to 10-year follow-up after PCI with DES, female patients are at increased risk of early myocardial infarction, receive fewer repeat revascularizations, and have no difference in cardiovascular mortality compared with male patients.

Revascularization strategies in patients with multivessel coronary artery disease: a Bayesian network meta-analysis.

Summary Treatment modalities for multivessel disease have rapidly evolved, yet the preferred strategy remains controversial. This meta-analysis compared outcomes after on-pump (ONCAB), off-pump coronary artery bypass grafting (OPCAB), percutaneous coronary intervention (PCI) or hybrid coronary revascularization. A comprehensive search for observational studies and randomized controlled trials published by August 2020 was performed. A Bayesian network meta-analysis was conducted for early (<30 days) and late (>12 months) outcomes. A total of 119 studies were included (n = 700 458 patients). The main analysis was confined to 31 randomized controlled trials (n = 24 932 patients). PCI was associated with lower early mortality [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.31–0.79] and stroke (OR 0.22, 95% CI 0.06–0.60) rates compared with ONCAB, whereas a reduced risk of early myocardial infarction was observed with OPCAB compared with ONCAB (OR 0.53, 95% CI 0.32–0.83). Late target vessel revascularization and major adverse cardiac and cerebrovascular events were both increased with PCI compared with ONCAB, OPCAB and hybrid coronary revascularization (by 127–203% and 59–64%, respectively), and late major adverse cardiac events were increased in PCI compared with ONCAB and OPCAB (by 64% and 59%). However, PCI was associated with a significantly lower risk of late stroke compared with ONCAB (OR 0.70, 95% CI 0.52–0.89). Sensitivity analyses (i) including observational studies and (ii) limiting to studies with recent cohorts confirmed the findings of the main analysis. Surgical approaches for revascularization remain superior to PCI in patients with multivessel disease. Hybrid coronary revascularization might be viable for some patients, although more evidence from randomized controlled trials is warranted.

Hypercholesterolemia as a factor in the risk stratification of patients with hypertension depending on the ITGA2 gene polymorphism

Abstract Mutation C807 in the ITGA2 gene is associated with the risk of early myocardial infarction, ischemic stroke, embolism, thrombosis after angioplasty and stenting of coronary arteries. Aim To study the relationship between ITGA2 gene polymorphism and increased risk of CAD in patients with hypertension and hypercholesterolemia Materials and methods 72 patients were included. Study involved patients with ACS, which developed on the background of hypertension, 32 patients also had coronary angiography and stenting. We used analysis of spontaneous and induced platelet aggregation, polymorphism of C807T of the ITGA2 gene was determined by polymerase chain reaction. Results At 82.5% of patients with ACS genotype ITGA 2 C/T was prevalent – 40.3%, T/T – 31.9%. Aggregation capability research in the studied groups has shown that patients of all groups had their degree of spontaneous aggregation significantly exceeding limits of control. Wherein, the highest indices were recorded in the T/T genotype group, which exceeded reference values by 3,02 times. AA-induced aggregation in the group of patients with T/T genotype exceeded indexes of the C/C group by 17.3%, while C/T group's rates-by 16.5% (p&amp;lt;0.05 in both cases). Studying the degree of collagen-induced aggregation, it was noted that the highest rates were recorded in T/T genotype group – 1.68 times higher than control group. Conclusion It is found that T allele of ITGA2 carrier is typical for 72.1% of patients with acute coronary syndrome and combined with spontaneous acceleration of platelet aggregation and increases sensitivity of platelets to ADP and collagen. Results allow us to consider the carrier of the T-allele as a marker of predisposition to thrombophilia. Funding Acknowledgement Type of funding sources: None.

Coronary lesion complexity in patients with heterozygous familial hypercholesterolemia hospitalized for acute myocardial infarction: data from the RICO survey

BackgroundAlthough patients with familial heterozygous hypercholesterolemia (FH) have a high risk of early myocardial infarction (MI), the coronary artery disease (CAD) burden in FH patients with acute MI remains to be investigated.MethodsThe data for all consecutive patients hospitalized in 2012–2019 for an acute MI and who underwent coronary angiography were collected from a multicenter database (RICO database). FH (n = 120) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). We compared the angiographic features of MI patients with and without FH (score 0–2) (n = 234) after matching for age, sex, and diabetes (1:2).ResultsAlthough LDL-cholesterol was high (208 [174–239] mg/dl), less than half of FH patients had chronic statin treatment. When compared with non-FH patients, FH increased the extent of CAD (as assessed by SYNTAX score; P = 0.005), and was associated with more frequent multivessel disease (P = 0.004), multiple complex lesions (P = 0.022) and significant stenosis location on left circumflex and right coronary arteries. Moreover, FH patients had more multiple lesions, with an increased rate of bifurcation lesions or calcifications (P = 0.021 and P = 0.036, respectively). In multivariate analysis, LDL-cholesterol levels (OR 1.948; 95% CI 1.090–3.480, P = 0.024) remained an independent estimator of anatomical complexity of coronary lesions, in addition to age (OR 1.035; 95% CI 1.014–1.057, P = 0.001).ConclusionsFH patients with acute MI had more severe CAD, characterized by complex anatomical features that are mainly dependent on the LDL-cholesterol burden. Our findings reinforce the need for more aggressive preventive strategies in these high-risk patients, and for intensive lipid-lowering therapy as secondary prevention.

Coronary lesion complexity in patients with familial hypercholesterolemia hospitalized for an acute myocardial infarction: data from the French RICO Survey

Abstract Background Although patients with familial heterozygous hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI), coronary artery disease (CAD) burden of FH patients with acute MI remains to be investigated. Methods All consecutive patients hospitalized for an acute MI in a multicenter database (RICO) from 2012–2017 who underwent coronary angiography were considered. FH (n=86) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥6). The angiographic features of FH patients were compared with patients without FH (score 0–2) (n=166), after matching for age, sex and diabetes (1:2). Results When compared with patients without FH, patients with FH had higher prevalence of personal and familial history of CAD (17 vs 5%, and 74 vs 5%, p=0.002 and p&amp;lt;0.001, respectively), and hypertension (54 vs 36%, p=0.006). Chronic statin treatment was used in only 45% of FH patients. At coronary angiography, FH had increased extent of CAD (SYNTAX score 11 (4–21) vs 8 (3–16), p=0.049) and multivessel disease (58% vs 43%, p=0.021). Significant stenosis was more frequent in left and right marginal coronary arteries. FH patients showed a trend toward more complex lesions, with less thrombus (28 vs 39%, p=0.076), but a 2 times higher rate of bifurcation lesions and calcifications (23 vs 12% and 20 vs 10%, p=0.021 and p=0.036). Conclusions This study addressing the coronary lesions features of FH patients with acute MI shows that FH patients had more severe CAD burden, and were characterized by complex anatomy features. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): ARS Bourgogne Franche Comté, CHU Dijon Bourgogne

Coronary lesion complexity in patients with familial hypercholesterolemia hospitalized for an acute myocardial infarction: Data from the French RICO Survey

Although patients with familial heterozygous hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI), coronary artery disease (CAD) burden of FH patients with acute MI remains to be investigated. All consecutive patients hospitalized for an acute MI in a multicenter database (RICO) from 2012–2017 who underwent coronary angiography were considered. FH ( n = 86) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). The angiographic features of FH patients were compared with patients without FH (score 0-2) ( n = 166), after matching for age, sex and diabetes (1:2). When compared with patients without FH, patients with FH had higher prevalence of personal and familial history of CAD (17 vs. 5%, and 74 vs. 5%, P = 0.002 and P < 0.001, respectively), and hypertension (54 vs. 36%, P = 0.006). Chronic statin treatment was used in only 45% of FH patients. At coronary angiography, FH had increased extent of CAD (SYNTAX score 11(4–21) vs. 8(3–16), P = 0.049) and multivessel disease (58% vs. 43%, P = 0.021). Significant stenosis was more frequent in left and right marginal coronary arteries. FH patients showed a trend toward more complex lesions, with less thrombus (28 vs. 39%, P = 0.076), but a 2 times higher rate of bifurcation lesions and calcifications (23 vs. 12% and 20 vs. 10%, P = 0.021 and P = 0.036). This study addressing the coronary lesions features of FH patients with acute MI shows that FH patients had more severe CAD burden, and were characterized by complex anatomy features.

2214Prevalence and severity of coronary disease in patients with familial hypercholesterolemia hospitalized for an acute myocardial infarction: data from the RICO survey

Abstract Aim Individuals with heterozygous familial hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH remains not well described. From a large database of a regional registry of acute MI, we aimed to address prevalence of FH and severity of CAD. Methods Consecutive patients hospitalized with MI in a multicentre database from 2001–2017 were considered. An algorithm, adapted from Dutch Lipid Clinic Network criteria, was built upon 4 variables (LDL-cholesterol (LDL-C) and lipid lowering agents, premature and family history of CAD) to identify FH probabilities. Results Among the 11624 patients included in the survey, 249 (2.1%) had probable/definite FH (score ≥6), and 2405 (20.7%) had possible FH (score 3–5). When compared with patients without FH (score 0–2), FH patients (score ≥6) were 20y younger (51 (46–57) vs 71 (61–80) y, p&lt;0.001), with a lower rate of hypertension (47 vs 59%, p&lt;0.001), diabetes (17 vs 25%, p&lt;0.001) and prior stroke (4 vs 8%, p=0.016), but a higher prevalence of smokers (56 vs 23%, p&lt;0.001), personal (20 vs 15%, p=0.02) or familial history of CAD (78 vs 18%, p&lt;0.001). Chronic statin treatment was only used in 48% of FH patients and ezetimibe in 8%. After adjustment for age, sex and diabetes, FH patients were characterized by increased extent of CAD (syntax score 11 (4–19) vs 7 (1–13), p&lt;0.001) and multivessel disease (55 vs 40%, p&lt;0.001). Conclusion In this large real world population of acute MI, a high prevalence of FH was found. FH patients were characterized by their young age associated with the severity of CAD burden and limited use of preventive lipid lowering therapy. Acknowledgement/Funding University Hospital Center Dijon Bourgogne, Agence Régionale de Santé Bourgogne Franche Comté, France

Prevalence, risk factor burden, and severity of coronary artery disease in patients with heterozygous familial hypercholesterolemia hospitalized for an acute myocardial infarction: Data from the French RICO survey

Individuals with heterozygous familial hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH remains not well described, especially for French patients. The objective of this study was to assess the prevalence of FH and severity of CAD from a large database of a French regional registry of acute MI. All consecutive patients hospitalized for an acute MI in a multicenter database from 2001 to 2017 were considered. FH was diagnosed using an algorithm adapted from the Dutch Lipid Clinic Network criteria. The prevalence and clinical features of FH and the severity of CAD were assessed. Among the 11,624 patients included in the study, the proportion of "probable/definite", "possible", and "unlikely" FH in patients with MI was 2.1% (n=249), 20.7% (n=2405), and 77.2% (n=8970), respectively. When compared with patients with "unlikely" FH, patients with "probable/definite" FH were 20years younger (51 vs 71, P<.001), with a lower rate of diabetes (17% vs 25%, P=.007) and a higher prevalence of personal and familial history of CAD. Chronic statin treatment was only used in 48% of FH patients and ezetimibe in 8%. After adjustment for age, sex, and diabetes, patients with FH were characterized by increased extent of CAD (SYNTAX score 11 vs 7, P<.001) and multivessel disease (55% vs 40%, P<.001). In this large cohort of French individuals, FH was common in patients with MI, associated with markedly early age of MI and severity of CAD burden and limited use of preventive lipid-lowering therapy.

Prevalence, characteristics and management of patients with familial hypercholesterolemia and acute myocardial infarction: Data from the RICO survey

Familial hypercholesterolemia (FH) is at very high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH in acute MI remains unclear. From a large database of a regional registry of acute MI, we aimed to address FH prevalence and CAD characteristics. Consecutive patients with AMI in the multicentre database (RICO survey) from 2001–2017 were considered. An algorithm, adapted from Dutch lipid clinic network criteria, was built upon 4 variables [LDL-cholesterol (C) level and chronic lipid lowering agents, premature and family history of CAD] to identify FH probabilities. Among the 11,624 patients included in the RICO survey, 249(2.1%) had probable/definite FH (score ≥ 6), and 2405(20.7%) had possible FH (score 3–5). When compared with patients without FH (score 0–2), FH patients (score ≥ 6) were ≈ 20y younger [51(46–57) vs. 71(61–80)y, P < 0.001], with a lower rate of hypertension (47 vs. 59%, P < 0.001), diabetes (17 vs. 25%, P < 0.001) and prior stroke (4 vs. 8%, P < 0.001), but a higher prevalence of smokers (56 vs. 23%, P < 0.001), personal (20 vs. 15%, P < 0.001) or familial history of CAD (78 vs. 18%, P < 0.001). Moreover, median LDL-C was ≈ twice higher [2.07(1.75–2.41) vs. 1.12(0.88–1.36) g/L]. Chronic statin was only used in less than half FH patients (48%). Among patients who underwent coronary angiography, FH patients were characterized by increased extent of CAD [syntax score 11(5–19) vs. 10(5–18), P < 0.001], and multivessel disease (55 vs. 54%, P < 0.001). Rate of revascularisation was higher (percutaneous coronary intervention: 76 vs. 70%, P < 0.001 and coronary artery bypass graft: 7 vs. 6%, P < 0.001). In this large real world population of acute MI, a high prevalence of FH was found. Moreover, FH patients were characterized by their young age associated with the severity of CAD burden and limited use of preventive lipid lowering therapy, suggesting the opportunity for prevention strategies.

Myelodysplastic Syndromes (MDS) Are an Independent Risk Factor for an Earlier Onset of Myocardial Infarction and Increased Mortality from Cardiovascular Disease (CVD)

Background:MDS originates from somatic mutations leading to clonally restricted hematopoiesis causing cytopenias and cellular dysplasia. Clonal expansion of these mutations in the absence of MDS criteria is known as clonal hematopoiesis of indeterminate potential (CHIP) and is considered a MDS precursor. CHIP is associated with increased risk of CVD, especially early onset myocardial infarction (MI) (Jaiswal S et al, NEJM, 2017). CVD events increase with clone size and a potential causal relationship involves accelerated atherosclerosis from an altered cell-mediated inflammatory response in the atherosclerotic plaque. It is suggested that MDS patients carry an increased risk of CVD mortality (Brunner AM et al, Bld Advances, 2017); it is unclear however if the increased risk of CVD persists even after developing MDS or is limited to CHIP. The influence of demographic factors & comorbidities on CVD among MDS patients is also unknown. The SEER Medicare tumor registry was queried to help answer these questions.Methods:Individuals 65 years or older from the SEER Medicare database with incident diagnosis of MDS between Jan. 1, 2004 and Dec. 31, 2014 (n=13,193) were identified. Demographic data and Charlson comorbidity index (CCI) 1 year prior to MDS diagnosis were analyzed. A control set of 5% randomly sampled non-cancer Medicare beneficiaries was paired to cases by propensity score matching (PSM) accounting for age, gender, race and urban/rural residence. The MDS diagnosis date served as the pseudodiagnosis date for non-cancer paired subjects. New onset MI or ischemic strokes (CVA) were identified with ICD9 and HCPCS codes in Medicare claims from date of diagnosis to death or study end. Incident cases were those with claims occurring after, and absent 1 year before, the MDS diagnosis date. Cumulative incidence functions were used to assess the risk of new events. Cox proportional hazards models, extended for time dependent covariates and coefficients, were used to evaluate clinical variables associated with new onset CVD and death.Results:MDS patients were predominantly male (55.2%) and non-hispanic whites (82.1%) from metropolitan areas (82.5%). Median age at diagnosis was 82 years (66 - 112) and median CCI score was 0 (0 - 13). The 5-year cumulative incidence of MI was 12.5% for MDS patients vs. 7% for controls (p<0.0001; Fig. 1). A diagnosis of MDS increases the risk of new onset MI by 1.4 (95% CI, 1.2 - 1.5). Other factors that significantly influenced the hazard ratio of MI were male sex (HR 1.3, 95% CI, 1.1 - 1.4), older age at diagnosis (HR 1.04 for each year over 65, 95% CI 1.03 - 1.05) and higher CCI (HR 1.2 for each point over 0, 95% CI 1.2 - 1.3). The effect of having MDS persisted after accounting for these factors in a multivariate Cox model and was more pronounced in patients with lower CCI (50% increase in 5-year MI rate in subgroup with CCI ≤1, Fig. 2). There was no difference in cumulative incidence of CVA between groups and MDS did not impact the risk of CVA. In multivariate analysis adjusted for age, gender and CCI, MDS was an independent risk factor for mortality in patients with new onset MI (HR 2.5, 95% CI, 1.1 - 3) and new onset CVA (HR 1.7, 95% CI, 1.5 - 1.9). Similarly, both MI (HR 2.8, 95% CI, 2.6 - 3.1) and CVA (HR 1.6, 95%CI 1.4 - 1.7) were independent risk factors for mortality in MDS patients (Fig. 3).Conclusion:Cumulative incidence of MI was higher in Medicare beneficiaries with MDS compared to non-cancer controls. The association of MI and MDS was even stronger in patients with a lower CCI score, particularly in patients with score ≤ 1. Thus, a diagnosis of MDS confers an independent risk for early MI in relatively healthy patients with little or no prior cardiovascular comorbidities. Furthermore, survival after a new CVD event was significantly reduced in subjects with MDS compared to controls. Evaluation and modification of cardiovascular risk factors is essential in patients with MDS and should be instituted early as it directly impacts their survival. Although we used validated methods, study limitations include relying on administrative claims from Medicare beneficiaries, absence of genetic or lifestyle information and unmeasured confounding factors not accounted for by PSM. While the risk of CVA was not impacted by a diagnosis of MDS, thrombocytopenia, anemia and transfusion dependence likely influenced the risk of these ischemic events and will be further explored as cofactors. [Display omitted] DisclosuresJanakiram:Seatle Genetics: Membership on an entity's Board of Directors or advisory committees.

Identification of familial hypercholesterolemia in patients with myocardial infarction: A Chinese cohort study

Familial hypercholesterolemia (FH) is marked by an elevated plasma cholesterol and risk of premature cardiovascular disease. An increased burden of FH is being realized. To provide data on FH in Chinese patients with myocardial infarction (MI) and its potential contribution to early MI. A total of 1843 consecutive patients undergoing coronary angiography with their first MI were recruited. The clinical FH was diagnosed using the Dutch Lipid Clinic Network criteria. The prevalence and clinical features of FH and the relationship of FH to risk of early MI were investigated. Of the 1843 patients, 48.2% were detected as premature MI (pMI, the onset age ≤55 years for men, ≤60 years for women). The prevalence of definite/probable FH reached 3.9% (7.1% in pMI and 0.9% in non-pMI). Furthermore, we found that the risk of pMI was significantly elevated in both definite/probable FH (vs. unlikely FH, odds ratio, 5.05 [1.10-23.23]) and possible FH (vs unlikely FH, odds ratio, 2.65 [1.22-5.77]), independently from classical risk factors and medications. Additionally, patients with definite/probable FH occurred 10years younger than those with unlikely FH in the onset age of MI (48.63±1.20 vs 58.35±0.30years, P<.001). When considered in subgroup of pMI or non-pMI, an early onset of MI was also observed in definite/probable FH (pMI, 45.83±0.89 vs 47.87±0.34years; non-pMI, 60.75±1.96 vs 65.07±0.22years; both P<.05). The prevalence of FH among Chinese patients with MI appeared common, particularly among those with pMI. The phenotypic FH might significantly promote the early onset of MI.

Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk

We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family.

0133 : Identifying familial hypercholesterolemia from registries of patients with acute myocardial infarction: an algorithm-based approach

Familial hypercholesterolemia (FH) is at very high risk of early myocardial infarction (MI). The prevalence of FH, which is estimated to be at least 1:500 in the general population, remains unclear in patients with acute MI. From databases of 3 French regional and nationwide registries of acute MI (RICO and FAST-MI 2005 and 2010, respectively), we aimed to determine FH prevalence by developing a specific algorithm. Consecutive patients with AMI ≤48 hours of onset included 1) in FAST-MI : during a one-month period in 223 institutions at the end of 2005 and 213 institutions at the end of 2010, and 2) in RICO :from January 2001 – December 2013 (≈ 13 y), were considered in the 3 databases. The algorithm was adapted from Dutch lipid clinic network criteria and was build upon 4 variables (i.e. LDL level and previous use of lipid lowering medications, premature and family history) to identify FH probability. The LDL level was adjusted on each type of lipid lowering medications and the probability of FH was defined taking into account missing data rate. Among the 7484 patients included in the RICO registry, 29.1% had premature vascular disease, 29.7% had familial history, 19.9% were under lipid lowering medications and 9.7% had LDL ≥5 mmol/L. FH prevalence was calculated as unlikely (72.6%), possible (24.6%) and probable /definite (2.8%). From the 1957 patients from FAST-MI 2005 with all data available, 29.7% had premature CV disease, 23% had a family history, 26.6% were on LLDs, and 5.4% had LDL ≥5 mmol/l. FH prevalence was calculated as unlikely (77.9%), possible (19.4%) and probable /definite (2.7%). In the 2223 patients from FASTMI 2010, 32.2% had premature CV disease, 24.9% had a family history, 28.1% were on LLDs, and 5.0% had LDL ≥5 mmol/l. FH prevalence was calculated as unlikely (75.7%), possible (21.5%) and probable /definite (2.7%). Our 4-variable algorithm yielded concordant results to determine FH probability in 3 different cohorts of AMI patients. In this large population reflecting routine clinical practice in acute MI, a high prevalence of FH was found, suggesting the opportunity for prevention strategies. The author hereby declares no conflict of interest

0132: Identifying familial hypercholesterolemia from registries of patients with acute myocardial infarction: an algorithm-based approach

Familial hypercholesterolemia (FH) is at very high risk of early myocardial infarction (MI). The prevalence of FH, which is estimated to be at least 1:500 in the general population, remains unclear in patients with acute MI. From databases of 2 French regional and nationwide registries of acute MI (RICO and FAST-MI, respectively), we aimed to determine FH prevalence by developing a specific algorithm. Consecutive patients with AMI ≤48 hours of onset included 1) in FAST-MI: during a one-month period in 213 institutions at the end of 2005 and 2) in RICO: from January 2001 December 2013 (≈13y), were considered in the 2 databases. The algorithm was adapted from Dutch lipid clinic network criteria and was build upon 4 variables (i.e. LDL level and previous use of lipid lowering medications, premature and family history) to identify FH probability. The LDL level was adjusted on each type of lipid lowering medications and the probability of FH was defined taking into account missing data rate. Among the 7484 patients included in the RICO registry, 29.1% had premature vascular disease, 29.7% had familial history, 19.9% were under lipid lowering medications and 9.7% had LDL ≥5mmol/L. FH prevalence was calculated as unlikely (72.6%), possible (24.6%) and probable /definite (2.8%). Our 4-variables algorithm is relevant to determine FH probability in databases from MI registries. In this large population reflecting routine clinical practice in acute MI, a high prevalence of FH was found, suggesting the opportunity for prevention strategies.

Triglyceride-rich lipoproteins and coronary artery disease risk: new insights from human genetics.

Despite ample success in reducing coronary artery disease (CAD) risk through reduction of low-density lipoprotein cholesterol (LDL-C), there remains substantial residual risk.1–4 Recent prospective studies have demonstrated that elevated triglycerides (TGs) are independent predictors of CAD risk.5–9 Furthermore, TGs are strongly associated with incident CAD events in patients with low LDL-C levels treated with statin.10 Thus, triglyceride-rich lipoproteins (TRLs) offer a potentially orthogonal risk factor to LDL-C for lowering CAD risk, but only if TRLs are causally associated with atherosclerotic disease.11 Human genetics has the potential to reveal the causal relationships of biomarkers found to be associated with disease outcomes.12–15 For example, genetic variants associated with plasma LDL-C levels are consistently associated with CAD risk in the right direction,15–18 consistent with a causal relationship. Importantly, similar studies have causally implicated the key TG-regulating enzyme lipoprotein lipase (LPL) in CAD risk. A common gain-of-function LPL variant, S447X, confers an antiatherogenic lipid profile characterized by low levels of TGs, and in several studies, it has been associated with lower incidence of vascular disease or myocardial infarction (MI).19–25 Conversely, several loss-of-function (LOF) LPL variants associated with elevated TG levels have been reported to be associated with increased CAD risk.21,26 Furthermore, multiple genome-wide association studies in the last 5 years have identified common noncoding variants at the LPL gene locus associated with both TG and CAD risk in the same direction.27–29 Beyond LPL itself, common variants that influence TG levels are significantly associated with CAD risk even after adjusting for their effects on other lipid traits.30 Do et al30 surveyed 185 single-nucleotide polymorphisms (SNPs) that were genome-wide significantly associated with ≥1 plasma lipid trait and identified a subset of …

VAMP-8 gene variant is associated with increased risk of early myocardial infarction

IntroductionSingle nucleotide polymorphism in the 3’ untranslated region of the vesicle-associated membrane protein gene (VAMP-8) has been associated with increased risk of early-onset myocardial infarction (MI). In this study the risk of early onset MI conferred by VAMP-8 gene polymorphism was investigated in a group of 171 male subjects.Material and methodsMale patients with a history of MI who underwent coronary angiography were enrolled and divided into early (incident < 55 years of age) and late (incident ≥ 55 years of age) MI onset groups. Apart from the RFLP-PCR based analysis of the VAMP-8 variant, history of hypertension, lipid abnormalities, smoking and body mass index were recorded. In statistical analyses odds ratios and relative risk were used as a measure of genotype-MI association while logistic regression was implemented for evaluation of MI risk factor strength.ResultsVAMP-8 A allele frequency proved to be significantly higher in the early-onset MI group and conferred higher relative risk of early MI in the investigated cohort, when calculated for the individual A allele (p = 0.029). In logistic regression analyses no association between risk genotypes and traditional risk factors was observed.ConclusionsIn this study VAMP-8 A variant was identified as a risk allele for early MI in male subjects.

Strong association of the APOA5-1131T>C gene variant and early-onset acute myocardial infarction

BackgroundEpidemiological studies support the role for a strong genetic component in the occurrence of early-onset myocardial infarction (MI), although the specific genetic variants responsible for familial clustering remain largely unknown. MethodsThe Italian study of early-onset MI is a nationwide case-control study involving 1864 case patients <45 years old who were hospitalized for a first MI, and age/sex/place of origin-matched controls (n=1864). We investigated the association between early-onset MI, lipid levels and 20 single nucleotide polymorphisms (SNPs) in the candidate genes ADIPOQ, APOA5, ALOX5AP, CYBA, IL6, LPL, PECAM1, PLA2G2A and PLA2G7, chosen because of previously reported associations with Coronary Heart Disease (CHD) or with CHD risk factors. ResultsOf all the SNPs investigated, APOA5-1131T>C [(rs662799), minor allele frequency 0.084 (95% confidence interval (CI) 0.07–0.09)] alone showed a statistically significant association with risk of early-onset MI (p=6.7×10−5), after Bonferroni correction, with a per C allele odds ratio of 1.44 (95% CI 1.23–1.69). In controls, APOA5-1131T>C was significantly associated with raised plasma triglyceride levels (p=0.001), compared with non-carriers, the per C allele increase being 11.4% (95% CI 4–19%), equivalent to 0.15mmol/L (95% CI 0.11–0.20mmol/L). In cases, the association with early MI risk remained statistically significant after adjustment for triglycerides (p=0.006). ConclusionsThe APOA5-1131C allele, associated with higher fasting triglyceride levels, strongly affects the risk for early-onset MI, even after adjusting for triglycerides. This raises the possibility that APOA5-1131T>C may affect the risk of early MI over and above effects mediated by triglycerides.

Matrix metalloproteinase 1 promoter polymorphisms and risk of myocardial infarction: a case–control study in a Spanish population

Inherited and acquired risk factors contribute to the development of the atherosclerotic lesion and its most common clinical manifestation, myocardial infarction (MI). Multiple studies have suggested a role for matrix metalloproteinases (MMPs) in atherosclerosis, and several functional polymorphisms in the MMP-1 gene have been linked to the risk of MI. The aim of this study was to evaluate the association between MMP-1 promoter polymorphisms and early MI in a Spanish cohort. We carried out a case-control study with 261 unrelated patients who had suffered an MI before 55 years of age and 194 healthy controls, all male and smokers. The genotypes for the three MMP-1 promoter polymorphisms -1607 1G/2G, -519 A/G, and -340 T/C were determined through PCR-restriction fragment length polymorphism. Allelic, genotypic, and haplotypic frequencies were statistically compared between groups. Frequencies of the three polymorphisms did not differ between patients and controls. The -1607 1G/2G and -519 A/G variants were in linkage disequilibrium. Analysis of the haplotype frequencies showed significant associations of the 2G(-1607)-G(-519)-T(-340) (odds ratio = 2.40; 95% confidence interval = 1.27-4.55; P<0.006) and 1G(-1607)-G(-519)-T(-340) (odds ratio = 0.68; 95% confidence interval = 0.50-0.94; P<0.05) haplotypes with the risk of early MI. MMP-1 promoter polymorphisms are associated with the risk of early MI in a Spanish population of smoking males.

Simple versus complex stenting strategy for coronary artery bifurcation lesions in the drug-eluting stent era: a meta-analysis of randomised trials

Background:Coronary bifurcation lesions remain a challenge for interventional cardiologists and the optimal stenting strategy has not been established in the current drug-eluting stent (DES) era. This study compared two strategies...

Coronary bifurcation lesions: To stent one branch or both? A meta-analysis of patients treated with drug eluting stents

Background In the treatment of coronary bifurcation lesions (CBL), with drug eluting stents (DES), we sought to compare angiographic and clinical outcomes of a simple strategy of stenting main vessel only with balloon dilatation of the side branch with a complex strategy of stenting both branches. Methods We performed a meta-analysis of six studies, randomized (three) or prospective observational (three), including 963 patients, that directly compared the simple strategy to the complex strategy, in the treatment of CBL with DES. Results Final minimal lumen diameter (MLD) of the side branch was significantly smaller in the simple strategy group [WMD − 0.50 mm, 95% CI (− 0.76, − 0.24), p < 0.00001]. The risk of main vessel restenosis [RR 0.66, 95% CI (0.38–1.17), p = 0.16], side branch restenosis [RR 0.62, 95% CI (0.24–1.56), p = 0.31], follow up death [RR 0.60, 95% CI (0.19–1.86), p = 0.38], follow up myocardial infarction [RR 0.71, 95% CI (0.46–1.10), p = 0.13], or target vessel revascularization [RR 0.90, 95% CI (0.56–1.46), p = 0.67] was similar between the two strategies. The simple strategy showed a trend to a lower risk of early myocardial infarction [RR 0.65, 95% CI (0.41–1.05), p = 0.08]. Conclusion In the treatment of unselected CBL with DES, the complex strategy does not penalize angiographic and clinical outcomes compared to the simple strategy. Further randomized studies are needed to assess the benefit of simple or complex strategy in the treatment of specific subsets of bifurcated lesions.