Large-Scale Screening for Monogenic and Clinically Defined Familial Hypercholesterolemia in Iceland.

Objective: Familial hypercholesterolemia (FH) is traditionally defined as a monogenic disease characterized by severely elevated LDL-C (low-density lipoprotein cholesterol) levels. In practice, FH is commonly a clinical diagnosis without confirmation of a causative mutation. In this study, we sought to characterize and compare monogenic and clinically defined FH in a large sample of Icelanders. Approach and Results: We whole-genome sequenced 49 962 Icelanders and imputed the identified variants into an overall sample of 166 281 chip-genotyped Icelanders. We identified 20 FH mutations in LDLR, APOB, and PCSK9 with combined prevalence of 1 in 836. Monogenic FH was associated with severely elevated LDL-C levels and increased risk of premature coronary disease, aortic valve stenosis, and high burden of coronary atherosclerosis. We used a modified version of the Dutch Lipid Clinic Network criteria to screen for the clinical FH phenotype among living adult participants (N=79 058). Clinical FH was found in 2.2% of participants, of whom only 5.2% had monogenic FH. Mutation-negative clinical FH has a strong polygenic basis. Both individuals with monogenic FH and individuals with mutation-negative clinical FH were markedly undertreated with cholesterol-lowering medications and only a minority attained an LDL-C target of <2.6 mmol/L (<100 mg/dL; 11.0% and 24.9%, respectively) or <1.8 mmol/L (<70 mg/dL; 0.0% and 5.2%, respectively), as recommended for primary prevention by European Society of Cardiology/European Atherosclerosis Society cholesterol guidelines. Conclusions: Clinically defined FH is a relatively common phenotype that is explained by monogenic FH in only a minority of cases. Both monogenic and clinical FH confer high cardiovascular risk but are markedly undertreated.

Multimorbidity and Readmissions in Older People with Acute Coronary Syndromes.

AIMS: This study aimed to examine the multimorbidity as well as the 30-day and 1-year readmission rates in a large, unselected cohort of elderly patients with acute coronary syndrome (ACS). METHODS AND RESULTS: All patients ≥70 years hospitalized due to ACS during January 1, 2006, to December 31, 2013, and registered in the SWEDEHEART registry were included. In-hospital multimorbidity and disease burden were determined. Outcomes included 30-day and 1-year all-cause mortality, any readmission, and readmissions due to ACS, heart failure, ischaemic stroke or transient ischaemic attack (TIA), and bleeding events. Out of 80,176 patients, 25.6% had ST-elevation myocardial infarction (STEMI) and 74.4% non-ST-segment elevation ACS (NSTE-ACS). The mean age was 79.8 (±6.4 standard deviation) and 43.4% were women. Multimorbidity, or two chronic diseases, was present in 67.7%, thereof in 53.0% of STEMI patients and 72.7% of NSTE-ACS patients. In-hospital mortality was 7.0%. Of the 74,577 patients who survived to discharge, 24.6% were readmitted within 30 days and 59.5% were readmitted during the following year. Multimorbid patients had a higher risk of readmissions than those without multimorbidity. Multimorbid STEMI patients were admitted the following year in 56.2% of cases compared to 44.5% of STEMI patients without multimorbidity, adjusted odds ratio (OR) 1.35 (95% confidence interval: 1.26-1.45). Multimorbid patients with NSTE-ACS were readmitted in 63.4% of cases the following year compared with 49.1% of those without multimorbidity, adjusted OR 1.42 (1.35-1.50). More than half of the readmissions were due to cardiovascular causes (ACS, stroke, TIA, or heart failure) or bleeding events. CONCLUSIONS: Older people with ACS have a high multimorbidity burden and a high readmission rate both within 30 days and 1 year. Half of the readmissions were due to a cardiovascular event or a bleeding event. The presence of multimorbidity increases the risk of readmissions for patients with ACS. As hospital admissions are costly for the health care system and can include risks, especially for older patients, there may be opportunities in better risk stratifying this group at discharge for subsequent decrease in readmission rates.

Outcomes after STEMI in old multimorbid patients with complex health needs and the effect of invasive management.

BACKGROUND: The aim of this study was to assess one-year outcomes of invasive and non-invasive strategies in ST-elevation myocardial infarction (STEMI) among multimorbid older people with complex health needs. METHODS: We included patients, registered between 2006 and 2013 in the SWEDEHEART registry, who were 70 years old or older with STEMI, had multimorbidity and complex health needs and were discharged alive. The one-year outcomes of patients who underwent invasive strategy (examined with coronary angiography ≤14 days) were compared to those who did not. The primary event was a composite of all-cause death, admission due to new acute coronary syndrome, stroke or transient ischemic attack. RESULTS: We identified patients, and 1089 were managed invasively and 570 non-invasively. The mean age was 79 years and 83 years in the 2 groups, respectively. After multivariable adjustment for baseline differences between the groups, including propensity scores, the primary event occurred in 31% of patients in the invasive group and 55% in the non-invasive group, adjusted hazard ratio (95% confidence intervals): 0.67 (0.54-0.83). One-year mortality was 18% in the invasive group and 45% in the non-invasive group, adjusted hazard ratio 0.51 (0.39-0.65). CONCLUSIONS: Multimorbid older people with complex health needs and STEMI had high rates of new ischemic events and death. In this cohort of older, high risk STEMI patients, an invasive strategy was associated with lower event rates. Randomized studies are needed to clarify whether these high risk patients who might benefit from invasive care are being managed too conservatively.

Outcomes 1 year after thrombus aspiration for myocardial infarction.

BACKGROUND: Routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) has not been proved to reduce short-term mortality. We evaluated clinical outcomes at 1 year after thrombus aspiration. METHODS: We randomly assigned 7244 patients with STEMI to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone, in a registry-based, randomized clinical trial. The primary end point of all-cause mortality at 30 days has been reported previously. Death from any cause at 1 year was a prespecified secondary end point of the trial. RESULTS: No patients were lost to follow-up. Death from any cause occurred in 5.3% of the patients (191 of 3621 patients) in the thrombus-aspiration group, as compared with 5.6% (202 of 3623) in the PCI-only group (hazard ratio, 0.94; 95% confidence interval [CI], 0.78 to 1.15; P=0.57). Rehospitalization for myocardial infarction at 1 year occurred in 2.7% and 2.7% of the patients, respectively (hazard ratio, 0.97; 95% CI, 0.73 to 1.28; P=0.81), and stent thrombosis in 0.7% and 0.9%, respectively (hazard ratio, 0.84; 95% CI, 0.50 to 1.40; P=0.51). The composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis occurred in 8.0% and 8.5% of the patients, respectively (hazard ratio, 0.94; 95% CI, 0.80 to 1.11; P=0.48). The results were consistent across all the major subgroups, including grade of thrombus burden and coronary flow before PCI. CONCLUSIONS: Routine thrombus aspiration before PCI in patients with STEMI did not reduce the rate of death from any cause or the composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis at 1 year. (Funded by the Swedish Research Council and others; TASTE ClinicalTrials.gov number, NCT01093404.).

Gender differences in coronary angiography, subsequent interventions, and outcomes among patients with acute coronary syndromes.

BACKGROUND: The objective was to investigate whether gender disparities are found in referrals of patients with acute coronary syndromes to percutaneous coronary interventions (PCIs) or coronary artery bypass grafting (CABG) and, furthermore, to study gender differences in complications and mortality. METHODS: All consecutive coronary angiographies (CAs) and PCIs performed in Sweden and Iceland are prospectively registered in the Swedish Coronary Angiography and Angioplasty Registry. For the present analysis, data of patients with acute coronary syndromes, enrolled in 2007-2011, were used to analyze gender differences in revascularization, in-hospital complications, and 30-day mortality. RESULTS: A total of 106,881 CAs were performed during the study period. In patients with significant coronary artery disease, the adjusted odds ratio (OR) for women to undergo PCI compared with men was 0.95 (95% CI 0.92-0.99) and 0.81 (0.76-0.87) for referrals to CABG. In patients with 1-vessel disease, women were less likely to undergo PCI than men, but women with 2- or 3-vessel or left main stem disease were more likely to undergo PCI. All in-hospital complications after CA followed by PCI were more frequent among women (adjusted OR 1.58 [1.47-1.70]). There was no gender difference in adjusted 30-day mortality after PCI (1.02 [0.92-1.12]) and after CABG (0.97 [0.72-1.31]). CONCLUSIONS: After CA showing 1-vessel disease, women as compared with men were less likely to undergo PCI. In the group with 2- or 3-vessel disease or left main stem stenosis, women were more likely to undergo PCI but less likely to undergo CABG. However, there was no gender difference in 30-day mortality.

Thrombus aspiration during ST-segment elevation myocardial infarction.

BACKGROUND: The clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. METHODS: We conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days. RESULTS: No patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI. CONCLUSIONS: Routine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.).

Common sequence variants associated with coronary artery disease correlate with the extent of coronary atherosclerosis.

OBJECTIVE: Single-nucleotide polymorphisms predisposing to coronary artery disease (CAD) have been shown to predict cardiovascular risk in healthy individuals when combined into a genetic risk score (GRS). We examined whether the cumulative burden of known genetic risk variants associated with risk of CAD influences the development and progression of coronary atherosclerosis. APPROACH AND RESULTS: We investigated the combined effects of all known CAD variants in a cross-sectional study of 8622 Icelandic patients with angiographically significant CAD (≥ 50% diameter stenosis). We constructed a GRS based on 50 CAD variants and tested for association with the number of diseased coronary arteries on angiography. In models adjusted for traditional cardiovascular risk factors, the GRS associated significantly with CAD extent (difference per SD increase in GRS, 0.076; P=7.3 × 10(-17)). When compared with the bottom GRS quintile, patients in the top GRS quintile were roughly 1.67× more likely to have multivessel disease (odds ratio, 1.67; 95% confidence interval, 1.45-1.94). The GRS significantly improved prediction of multivessel disease over traditional cardiovascular risk factors (χ(2) likelihood ratio 48.1; P<0.0001) and modestly improved discrimination, as estimated by the C-statistic (without GRS versus with GRS, 64.0% versus 64.8%) and the integrated discrimination improvement (0.52%). Furthermore, the GRS associated with an earlier age at diagnosis of angiographic CAD. These findings were replicated in an independent sample from the Emory Biobank study (n=1853). CONCLUSIONS: When combined into a single GRS, known genetic risk variants for CAD contribute significantly to the extent of coronary atherosclerosis in patients with significant angiographic disease.

Impact of thrombus aspiration during ST-Elevation Myocardial Infarction: a six month composite endpoint and risk of stroke analyses of the TASTE trial.

BACKGROUND: Routine thrombus aspiration during primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) did not reduce the primary composite endpoint in the "A Randomised Trial of Routine Aspiration ThrOmbecTomy With PCI Versus PCI ALone in Patients With STEMI Undergoing Primary PCI" (TOTAL) trial. We aimed to analyse a similar endpoint in "The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia" (TASTE) trial up to 180 days. METHODS: In TASTE, 7244 patients with STEMI were randomised to thrombus aspiration followed by PCI or to PCI alone. We analysed the quadruple composite endpoint of cardiovascular death, cardiogenic shock, rehospitalisation for myocardial infarction, or new hospitalisation for heart failure. Furthermore, an extended net-benefit composite endpoint including stent thrombosis, target vessel revascularization or stroke within 180 days was analysed. RESULTS: The primary quadruple composite endpoint occurred in 8.7 % (316 of 3621) in the thrombus aspiration group compared to 9.3 % (338 of 3623) in the PCI alone group (hazard ratio (HR), 0.93; 95 % confidence interval (CI); 0.80 - 1.09, P = 0.36) and the extended net-benefit composite endpoint in 12.0 % (436) vs. 13.2 % (479) (HR, 0.90; 95 % CI; 0.79 - 1.03, P = 0.12). Stroke within 30 days occurred in 0.7 % (27) vs. 0.7 % (24) (HR, 0.89; 95 % CI; 0.51-1.54, P = 0.68). CONCLUSIONS: A large and an extended composite endpoint analysis from the TASTE trial did not demonstrate any clinical benefit of routine thrombus aspiration during PCI in patients with STEMI. There was no evidence of an increased risk of stroke with thrombus aspiration.

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries.

AIMS: Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. METHODS AND RESULTS: A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. CONCLUSION: Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encouraged.

Type D personality is associated with impaired psychological status and unhealthy lifestyle in Icelandic cardiac patients: a cross-sectional study.

BACKGROUND: Type D (distressed) personality has been associated with adverse cardiac prognosis and poor emotional well-being in cardiac patients, but it is still unclear what mechanisms link Type D personality with poor clinical outcomes in cardiac patients. In the present cohort of Icelandic cardiac patients, we examined potential pathways that may explain this relationship. The objectives were to examine 1) the association between Type D personality and impaired psychological status, and to explore whether this association is independent of disease severity; and 2) the association between Type D personality and an unhealthy lifestyle. METHODS: A sample of 268 Icelandic coronary angiography patients (74% males (N = 199); mean age 62.9 years (SD 10.5), range 28-85 years) completed the Type D Scale (DS14), Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS) at hospitalization. Health-related behaviors were assessed 4 months following angiography. Clinical data were collected from medical files. RESULTS: Type D personality was associated with an increased risk of anxiety (OR 2.97, 95% CI:1.55-5.69), depression (OR 4.01, 95% CI:1.42-11.29), and stress (OR 5.99, 95% CI:3.08-11.63), independent of demographic variables and disease severity. Furthermore, fish consumption was lower among Type Ds, as 21% of Type Ds versus 5% of non-Type Ds consumed fish < 1 a week (p < 0.001). Type D patients were also more likely to smoke at follow-up (22% versus 10%, p = 0.024) and to use antidepressants (17% versus 9%, p = 0.049) and sleeping pills (49% versus 33%, p = 0.019) compared to non-Type Ds. Type D personality was not associated with other health-related behaviors, aside from trends towards less fruit and vegetable consumption, and more weight gain. CONCLUSION: Type D personality was associated with psychological distress and an unhealthy lifestyle in Icelandic cardiac patients. Future studies should further investigate the association between Type D personality and health-related behaviors.