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.

Validity of Type D personality in Iceland: association with disease severity and risk markers in cardiac patients.

Type D personality has been associated with poor prognosis in cardiac patients. This study investigated the validity of the Type D construct in Iceland and its association with disease severity and health-related risk markers in cardiac patients. A sample of 1,452 cardiac patients completed the Type D scale (DS14), and a subgroup of 161 patients completed measurements for the five-factor model of personality, emotional control, anxiety, depression, stress and lifestyle factors. The Icelandic DS14 had good psychometric properties and its construct validity was confirmed. Prevalence of Type D was 26-29%, and assessment of Type D personality was not confounded by severity of underlying coronary artery disease. Regarding risk markers, Type D patients reported more psychopharmacological medication use and smoking, but frequency of previous mental problems was similar across groups. Type D is a valid personality construct in Iceland, and is associated with health-related risk markers, but not cardiac disease severity.

Decreasing case fatality in myocardial infarction is explained by improved medical treatment.

OBJECTIVE: Treatment of ST-elevation myocardial infarction (STEMI) has changed significantly over the past two decades. We investigated the effect of these changes on one-year mortality. METHODS AND RESULTS: All hospital admissions for STEMI in Reykjavik, Iceland, during the calendar years of 1986, 1996 and 2006 were studied. One-year mortality was related to changes in the use of reperfusion strategies and medication at hospital discharge. One-year mortality decreased from 26.3% in 1986 and 19.7% in 1996 to 12.9% in 2006 (P= 0.001). Cox proportional hazard analysis showed that aspirin (HR 0.29), the use of reperfusion therapy (HR 0.51) and beta-blockers at hospital discharge (HR 0.53) were the strongest factors to explain the mortality reduction while the use of diuretics (HR 1.42) and age (HR 1.06) were related to increased one-year mortality. CONCLUSIONS: The reduction in one-year mortality after myocardial infarction during the last two decades is explained by improved medical management with aspirin, beta-blockers and aggressive reperfusion therapy. Diuretic therapy, reflecting congestive heart failure, and increased age have negative effects on survival.

Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE trial). A multicenter, prospective, randomized, controlled clinical registry trial based on the Swedish angiography and angioplasty registry (SCAAR) platform. Study design and rationale.

BACKGROUND: In ST-elevation myocardial infarction (STEMI), distal embolization of thrombus material often precludes restoration of normal coronary artery flow. Small-scaled studies have demonstrated that intracoronary thrombus aspiration improves flow and myocardial perfusion, but only one larger randomized single-center study has suggested a survival benefit. Thrombus aspiration is widely used in clinical practice and is recommended by international guidelines despite limited evidence. METHODS/DESIGN: The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia is a multicenter, prospective, randomized, controlled, clinical open-label trial based on the Swedish angiography and angioplasty registry (SCAAR) platform with blinded evaluation of end points. A total of 5,000 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) will randomly be assigned either to conventional PCI or to thrombus aspiration followed by PCI. SCAAR will be used as the platform for randomization, allowing a broad population of all-comers in the registry network to be enrolled. All follow-up will also be done in SCAAR and other national registries. The primary end point is time to all-cause death at 30 days. DISCUSSION: The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial is the largest trial to date to evaluate the effect of thrombus aspiration on death following PCI in patients with STEMI. We propose the term randomized clinical registry trial to describe the novel entity of using an online national registry as platform for case records, randomization, and follow-up.

Association of Genetically Predicted Lipid Levels With the Extent of Coronary Atherosclerosis in Icelandic Adults.

Importance: Genetic studies have evaluated the influence of blood lipid levels on the risk of coronary artery disease (CAD), but less is known about how they are associated with the extent of coronary atherosclerosis. Objective: To estimate the contributions of genetically predicted blood lipid levels on the extent of coronary atherosclerosis. Design, Setting, and Participants: This genetic study included Icelandic adults who had undergone coronary angiography or assessment of coronary artery calcium using cardiac computed tomography. The study incorporates data collected from January 1987 to December 2017 in Iceland in the Swedish Coronary Angiography and Angioplasty Registry and 2 registries of individuals who had undergone percutaneous coronary interventions and coronary artery bypass grafting. For each participant, genetic scores were calculated for levels of non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, based on reported effect sizes of 345 independent, lipid-associated variants. The genetic scores' predictive ability for lipid levels was assessed in more than 87 000 Icelandic adults. A mendelian randomization approach was used to estimate the contribution of each lipid trait. Exposures: Genetic scores for levels of non-HDL-C, LDL-C, HDL-C, and triglycerides. Main Outcomes and Measures: The extent of angiographic CAD and coronary artery calcium quantity. Results: A total of 12 460 adults (mean [SD] age, 65.1 [10.7] years; 8383 men [67.3%]) underwent coronary angiography, and 4837 had coronary artery calcium assessed by computed tomography. A genetically predicted increase in non-HDL-C levels by 1 SD (38 mg/dL [to convert to millimoles per liter, multiply by 0.0259]) was associated with greater odds of obstructive CAD (odds ratio [OR], 1.83 [95% CI, 1.63-2.07]; P = 2.8 × 10-23). Among patients with obstructive CAD, there were significant associations with multivessel disease (OR, 1.26 [95% CI, 1.11-1.44]; P = 4.1 × 10-4) and 3-vessel disease (OR, 1.47 [95% CI, 1.26-1.72]; P = 9.2 × 10-7). There were also significant associations with the presence of coronary artery calcium (OR, 2.04 [95% CI, 1.70-2.44]; P = 5.3 × 10-15) and loge-transformed coronary artery calcium (effect, 0.70 [95% CI, 0.53-0.87]; P = 1.0 × 10-15). Genetically predicted levels of non-HDL-C remained associated with obstructive CAD and coronary artery calcium extent even after accounting for the association with LDL-C. Genetically predicted levels of HDL-C and triglycerides were associated individually with the extent of coronary atherosclerosis, but not after accounting for the association with non-HDL cholesterol. Conclusions and Relevance: In this study, genetically predicted levels of non-HDL-C were associated with the extent of coronary atherosclerosis as estimated by 2 different methods. The association was stronger than for genetically predicted levels of LDL-C. These findings further support the notion that non-HDL-C may be a better marker of the overall burden of atherogenic lipoproteins than LDL-C.

Clinical evaluation and stress test have limited value in the diagnosis of in-stent restenosis.

OBJECTIVES: In-stent restenosis (ISR) is the main limitation of percutaneous coronary interventions (PCI), occurring in approximately 25% of cases. Although frequently asymptomatic, many PCI patients present with recurrent symptoms of chest pain at follow-up raising a clinical suspicion of ISR. The diagnosis of ISR can be challenging in these patients and difficult to rule out without repeat coronary angiography. DESIGN: We prospectively investigated the diagnostic accuracy of clinical evaluation and exercise stress testing to detect ISR as compared to coronary angiography, in a consecutive, unselected cohort of PCI patients. RESULTS: We studied 91 patients with a total of 143 stents. Clinical evaluation predicted ISR to be likely in 19% of cases and the exercise test was positive in 29%. The binary restenosis rate was 21%. Clinical evaluation had a positive predictive value of 29% and accuracy of 71%, while exercise stress testing had a positive predictive value of 19% and accuracy of 65%. CONCLUSION: In conclusion, we found the diagnostic accuracy of clinical evaluation to be low and not significantly improved by exercise stress testing when evaluating PCI patients for ISR.

[Acute coronary syndromes in Landspítali 2003-2012].

BACKGROUND: Marked changes in the epidemiology of acute coronary syndromes (ACS) have been observed over the last few decades in the Western Hemisphere. Incidence rates of ACS in Iceland 2003-2012 are presented. METHODS: All patients with unstable angina (UA), non ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarc-tion (STEMI) admitted to Landspitali were included in the study. Data were obtained from hospital records and changes during the period were examined. RESULTS: The total number of ACS cases was 7,502. STEMI incidence was reduced from 98/100,000 inhabitants in 2003 to 63 in 2012, a reduction of nearly 36%. Age standardized incidence rates of STEMI declined annually by 5.5% in men and 5.3% in women (p <0.05). Incidence of NSTEMI increased from 54 /100,000 inhabitants in 2003 to 93 in 2012. UA patients were 56/100,000 inhabitants in 2003, 115 in 2008 and 50 in 2012. No significant annual change in age-standardized incidence rates of NSTEMI and UA was observed. About 35% of patients with NSTEMI and 30% with STEMI and UA were female. The mean age of NSTEMI patients was 72 years, five years higher than patients with STEMI and UA. About 30% of -pat-ients were living outside of the capital region. CONCLUSIONS: 2003-2012 there was a significant 5% annual -decrease in the number of STEMI cases and a tendency to -increasing incidence of NSTEMI which by the end of the research period was the most common of the syndromes. An unusual development in the incidence of UA was observed. Possible effect of psychological stress in the society should be considered.

Assessing the Nationwide Impact of a Registry-Based Randomized Clinical Trial on Cardiovascular Practice.

BACKGROUND: Registry-based randomized clinical trials have emerged as useful tools to provide evidence on the comparative efficacy and safety of different therapeutic strategies. However, it remains unknown whether the results of registry-based randomized clinical trials have a sizable impact on daily clinical practice. We sought, therefore, to describe the temporal trends in thrombus aspiration (TA) use in Sweden before, during, and after dissemination of the TASTE trial (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) results. METHODS AND RESULTS: From January 1, 2006, to December 31, 2017, we included all consecutive patients with ST-segment-elevation myocardial infarction undergoing percutaneous revascularization in Sweden. All patients were registered in the Swedish Coronary Angiography and Angioplasty Registry. A total of 55 809 ST-segment-elevation myocardial infarction patients were included. TA use in Sweden substantially decreased after dissemination of TASTE results (from 39.8% to 11.8% during and after TASTE, respectively). Substantial variability in TA use across treating centers was observed before TASTE (TA use ranging from 0% to 70%), but after TASTE both the interhospital variability and the frequency of TA use were markedly reduced. A constant shift in medical practice was seen about 4 months after dissemination of the TASTE trial results. Time trends for all-cause mortality and definite stent thrombosis at 30 days were not associated with variations in TA use ( P values >0.05 using the Granger test). CONCLUSIONS: In Sweden, the results of the TASTE trial were impactful in daily clinical practice and led to a relevant decrease in TA use in ST-segment-elevation myocardial infarction patients undergoing percutaneous revascularization.

Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular diseases that has no established therapy. The attribute of Lp(a) that affects cardiovascular risk is not established. Low levels of Lp(a) have been associated with type 2 diabetes (T2D). OBJECTIVES: This study investigated whether cardiovascular risk is conferred by Lp(a) molar concentration or apolipoprotein(a) [apo(a)] size, and whether the relationship between Lp(a) and T2D risk is causal. METHODS: This was a case-control study of 143,087 Icelanders with genetic information, including 17,715 with coronary artery disease (CAD) and 8,734 with T2D. This study used measured and genetically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a) size), and a splice variant in LPA associated with small apo(a) but low Lp(a) molar concentration to disentangle the relationship between Lp(a) and cardiovascular risk. Loss-of-function homozygotes and other subjects genetically predicted to have low Lp(a) levels were evaluated to assess the relationship between Lp(a) and T2D. RESULTS: Lp(a) molar concentration was associated dose-dependently with CAD risk, peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size. Homozygous carriers of loss-of-function mutations had little or no Lp(a) and increased the risk of T2D. CONCLUSIONS: Molar concentration is the attribute of Lp(a) that affects risk of cardiovascular diseases. Low Lp(a) concentration (bottom 10%) increases T2D risk. Pharmacologic reduction of Lp(a) concentration in the 20% of individuals with the greatest concentration down to the population median is predicted to decrease CAD risk without increasing T2D risk.

[MINOCA in Iceland. Acute coronary syndrome in patients with normal or nonobstructive coronary arteries].

INTRODUCTION: The classical pathophysiological process underlying acute coronary syndromes has been considered to be plaque rup-ture followed by platelet activation and aggregation and subsequent thrombus formation leading to myocardial ischemia and infarction. A substantial number of patients with acute coronary syndromes appear to have normal or near normal (<50% stenosis) coronary arteries on angiography. Recently, this clinical entity has been coined MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries). The purpose of this paper is to describe the proportion of MINOCA among ACS patients in Iceland. MATERIAL AND METHODS: We performed a retrospective analysis of all admissions for acute coronary syndromes at Landspitali University Hospital, the single coronary catheterization facility in Iceland, during a five year period between 2012 and 2016. All patients admitted for STEMI or NSTEMI that turned out to have normal or near normal coronary arteries were consecutively included in the study. For each patient the diagnosis was re-evaluated according to further assessments using a diagnostic algorithm specially constructed for this study. RESULTS: During the five year study period 1708 patients were studied with coronary angiography during first hospitalization for STEMI or NSTEMI. Among these, 225 (13.2%) had normal or non-obstructive coronary arteries with less than 50% luminal narrowing. The final diagnosis of these patients were plaque erosion / rupture in 72 indi-viduals (32%), myocarditis in 33 (14.7%), takotsubo cardiomyopathy in 28 (12.4%), type II myocardial infarction in 30 (13.3%), vasospastic angina in 31 (13.8%) and other or undetermined cause in 31 (13.8%) patients. CONCLUSION: The proportion of MINOCA in Iceland is 13.2% of patients admitted for acute coronary syndromes. Plaque erosion / rupture was considered a likely cause in one third of patients with other causes beeing evenly distributed with approximately half that frequency. Identification of the underlying cause of MINOCA would become more accurate with a consistent use of cardiac magnetic resonance imaging in these patients as it provided a definitive diagnosis in all of those -studied.

[Acute myocardial infarction among Icelanders forty years old and younger 2005-2009. Comparison with a study carried out 1980-1984].

INTRODUCTION: While acute myocardial infarction  (AMI) mostly is a disease of the elderly it also affects younger individuals, often with serious consequenses. In 1980-1984 a study was carried out on the incidence, risk factors, infarct location and distribution of atherosclerosis among Icelanders forty years and younger with AMI. Here we present the results of a similar study carried out for the five year period 2005-2009. MATERIALS AND METHODS: Medical and autopsy records of all individuals, forty years and younger, diagnosed with AMI (I21 in ICD-10) at Landspitali, National University Hospital 2005-2009, or suffering sudden cardiac death in Iceland during the same period were reviewed. Blood tests, electrocardiograms, echocardiograms, coronary angiograms and autopsy results were reviewed with respect to AMI-criteria. Statistical comparisons of ratios and means were carried out using Chi-square test and T-test, respectively. RESULTS: 38 individuals 40 years and younger, 32 males and 6 females, fulfilled the diagnostic criteria of AMI. Calculated incidence for the population at risk was 10/100.000/year (14/100.000/year in 1980-1984) and the mean age ±S.D. was 36.7±3.9. Three (7.9%) died suddenly before reaching hospital but of the 35 hospitalised patients 30 day mortality was zero, compared to nine (23.7%) pre-hospital deaths and two (6.9%) hospital deaths in 1980-1984. Thus, combined pre-hospital and in-hospital (30 day) mortality was 28.9% and 7.9% in the previous and recent time periods, respectively (p=0.02). In 2005-2009, 77.1% had a smoking history and 31.4% were hypertensive compared to 97% and 6.9% in 1980-85 (p=0.026 and p=0.015, respectively). Body mass index (BMI) was higher in the later period, 28.6±4,8 kg/m2 compared to 26.1±3.6 (mean±S.D.; p=0.04) but s-cholesterol was lower, 5.1±1.4 mmol/L compared to 6.3±1.16 ( mean±S.D.; p<0.01). In both studies single coronary artery disease was the most common angiographic pattern and the left anterior descending artery most often involved. CONCLUSION: Our results show that in two surveys 25 years apart AMI patients 40 years and younger are most often men. Smoking and family history were the most prominent risk factors during both periods but hypertension and high BMI were more common in 2005-2009 than in 1980-1984. Prognosis, as indicated by combined pre-hospital and in-hospital (30 day) mortality has improved. Key words: Myocardial infarction, forty and younger, incidence, risk factors, mortality, time trend Correspondence: Gudmundur Thorgeirsson gudmth@landspitali.is.