BACKGROUND: Medication adherence (MA) is essential for achieving the benefits of guideline-directed medical therapy in heart failure, yet it is seldom assessed systematically in routine care. Understanding how patients experience and manage longterm medication use in everyday life is critical for designing effective, patient-centered MA support. METHODS: A qualitative study explored the experiences of patients with heart failure of factors influencing MA. Data were derived from 4 focus groups and 12 in-depth interviews with 27 participants (May 2022-November 2023) recruited from the Icelandic Heart Failure Registry and a cardiac rehabilitation program. Data were analyzed using inductive thematic analysis, supported by field notes and multidisciplinary review. RESULTS: Four interdependent themes emerged: (1) practical aspects of medication use, including daily routines, dose timing, MA aids, formulation challenges, and polypharmacy; (2) psychosocial influences, such as stress, mood, cognition, social support, and socioeconomic context; (3) interactions with the health care system and providers, including education, followup, access, costs, patient-provider relationships, and home support; and (4) disease-and medication-related factors, including symptoms, physical limitations, diuretic burden, and side effects. MA was most consistent when regimens aligned with daily life and when tolerability, follow-up, psychosocial needs, and costs were addressed proactively. CONCLUSIONS: Patients with heart failure experience MA as a dynamic process of integrating treatment into daily life rather than a matter of motivation alone. Effective MA support requires regimen simplification, explicit diuretic planning, psychosocial and cost screening, and coordinated multidisciplinary follow-up, including pharmacist involvement. These findings provide patient-derived evidence to inform heart failure-specific MA assessment in routine clinical practice.

BACKGROUND AND AIMS:This observational study investigated whether patients with coronary heart disease (CHD) in Europe are achieving the standards set by prevention and rehabilitation guidelines. Variability was studied: (i) between countries; (ii) between geographical risk regions; and (iii) attendance at cardiac rehabilitation (CR) with outcomes. METHODS:Observational study between September 2024- February 2026 in 160 hospitals across 27 countries. Geographical risk regions were defined as high, moderate or low based on WHO cardiovascular mortality data. RESULTS:Among 8590 patients with CHD (23.7% female), 17.1% were current smokers, 32.0% were obese and 33.5% reported low physical activity. 59.8% were above blood pressure target (systolic ≥ 130 and/or diastolic ≥ 80 mmHg), 82.7% were above LDL-C target (≥ 1.4 mmol/l), 32.8% had known diabetes of whom 42.2% had HbA1c ≥ 7% and 30.6% had chronic kidney disease. Prevalences of these risk factors were all highest in countries from high risk regions. 29.1% of patients attended at least one CR session, with country variability ranging from 0% to 79%, and differing by risk region (55.9% low risk, 29.7% moderate risk and 10.2% high risk; p < 0.001). Attendance at CR programme was associated with significantly better lifestyles, risk factor control and use of cardioprotective drugs. CONCLUSIONS:Most European patients are not achieving targets set by prevention guidelines. There is marked variability in CR attendance, evidence of inverse care with lowest attendance in highest risk regions, despite better outcomes for CR. These results inform the challenges for implementation of the first ESC guideline on CR.

BACKGROUND:Patients benefit from antiplatelet therapy after coronary-artery bypass grafting (CABG) for an acute coronary syndrome. Whether the addition of ticagrelor to aspirin, as compared with aspirin alone, further reduces the risk of adverse cardiovascular outcomes is unclear. METHODS:In this open-label, registry-based, clinical trial conducted at 22 Nordic cardiothoracic surgery centers, we randomly assigned patients in a 1:1 ratio to receive either ticagrelor plus aspirin or aspirin alone for 1 year after CABG for an acute coronary syndrome. The primary outcome was a composite of death, myocardial infarction, stroke, or repeat revascularization, evaluated at 1 year. A key secondary outcome was net adverse clinical events, defined as a primary-outcome event or major bleeding. RESULTS:A total of 2201 patients were randomly assigned to receive ticagrelor plus aspirin (1104 patients) or aspirin alone (1097 patients). The mean age of the patients was 66 years, and 14.4% were women. A primary-outcome event occurred in 53 patients (4.8%) in the ticagrelor-plus-aspirin group and 50 (4.6%) in the aspirin-alone group (hazard ratio, 1.06; 95% confidence interval [CI], 0.72 to 1.56; P = 0.77). Net adverse clinical events occurred in 9.1% of patients in the ticagrelor-plus-aspirin group and 6.4% in the aspirin-alone group (hazard ratio, 1.45; 95% CI, 1.07 to 1.97). Major bleeding occurred in 4.9% of patients in the ticagrelor-plus-aspirin group and 2.0% in the aspirin-alone group (hazard ratio, 2.50; 95% CI, 1.52 to 4.11). CONCLUSIONS:Among patients who underwent CABG for an acute coronary syndrome, ticagrelor plus aspirin did not result in a lower incidence of death, myocardial infarction, stroke, or repeat coronary revascularization than aspirin alone at 1 year. (Funded by the Swedish Research Council and others; TACSI ClinicalTrials.gov number, NCT03560310; EudraCT number, 2017-001499-43; EU Clinical Trials number, 2023-508551-40-00.).

Introduction: Cardiac amyloidosis (CA) arises from the deposition of misfolded amyloid proteins in the heart's extracellular matrix, leading to significant cardiac disease. Recent data suggest that CA is under recognised and advances in treatment have increased focus on this condition with the intention of implementing treatment earlier to improve prognosis. There is limited knowledge regarding the prevalence of Transthyretin-CA (ATTR-CA) on a national level, particularly in Iceland. Therefore, this study represents the first nationwide effort to evaluate the baseline characteristics, diagnostics, and treatment of ATTR-CA in Iceland. Methods: A retrospective study of all patients diagnosed with ATTR-CA in Iceland from 6 May 2013 to 11 March 2024 were identified in the Icelandic Cardiac Amyloid Registry (ICE-CAR) created in 2023 by heart failure (HF) specialists at Landspitali University Hospital in Reykjavik, Iceland. Diagnosis was based on different combinations of transthoracic echocardiography (TTE), an elevated Perugini score on bone scintigraphy and heart biopsies, as well measurements of free light chains, M-component measurements in blood and urine. Patients were grouped according to the National Amyloidosis Centre (NAC) prognostic staging system for ATTR-CA. Results: In total, 65 patients with ATTR-CA were identified (males n=60, females n=5, median age 81.4 years [IQR 75.5-85.5 years]), all wild-type and no mutant variant. Diagnosis was made with myocardial biopsy in 7 cases. Upon diagnosis, 83% of the patients had an interventricular septum thickness of ≥15mm and 92% showed a posterior wall thickness of ≥12mm. Approximately 57% of patients belonged to New York Heart Association (NYHA) functional class I-II. The HF phenotypes according to left ventricular ejection fraction (LVEF) were distributed as follows: reduced (HFrEF) n=24 (37%), mildly reduced (HFmrEF) n=9 (14%), preserved (HFpEF) n=29 (44.5%), and unknown LVEF n=3 (4.5%). A total of 54 patients had reported NAC stage: Stage I 23 (35.4%), Stage II 20 (30.8%), Stage III 11 (16.9%). Around 32% received disease modifying treatment. Conclusion Despite the low NYHA class observed in the study population, our findings in Iceland's nationwide assessment of ATTR-CA indicate more advanced age and lower LVEF at diagnosis compared to other studies. This highlights the critical need for early detection and appropriate therapeutic interventions in managing ATTR-CA.

Objectives Temporal trends in the incidence of ST-elevation myocardial infarction (STEMI) have been declining in many countries, while the incidence of non-ST elevation myocardial infarction (NSTEMI) has reached a plateau or even increased. The reasons for these changing trends have yet to be explained. We analysed these trends and short-term mortality from acute coronary syndromes in a nationwide cohort study over 35 years in Iceland. Design Retrospective cohort study using a national MI registry. Setting Iceland. Participants All cases of myocardial infarction in individuals aged 25–74 years in Iceland 1981–2015. Methods Each case was classified as STEMI, NSTEMI or no ECG taken. ECG recordings were classified according to Minnesota criteria. Outcome measures Trends of STEMI and NSTEMI incidence and 1-day and 28-day mortality were obtained from the National Death Registry. Results A total of 10 348 cases were identified (mean age 61 years, 76.4% male). These were categorised as STEMI (32.7%), NSTEMI (45.8%) and no ECG taken (21.5%). We detected a significant 3.7% annual decline in the incidence of first MI. The age-adjusted incidence of STEMI showed an 83.2% decline, most pronounced after 1994, while for NSTEMI the decline was 66.5%, reaching a plateau from the year 1989 onwards. In Iceland, the uptake of highly sensitive biomarkers was initiated in 1997 (cardiac troponin T) and 2012 (high-sensitive troponin T), respectively. Conclusions The different temporal trends in the incidence of STEMI and NSTEMI cannot be explained only by the uptake of highly sensitive biomarkers in 1997 and 2012. The change in population-level risk factor exposure is likely to have influenced atherosclerotic plaque burden and thrombotic mechanisms. Finally, increasing uptake of cardioprotective pharmacological and interventional therapy may have resulted in a primary preventive effect on plaque rupture and thrombosis and thus on the rates of STEMI and NSTEMI disproportionally.

Adhering to medication regimens is key behavior to alleviate symptoms and slow disease progression in heart failure (HF). This study explores cardiac healthcare providers' perceptions and experiences of factors influencing medication adherence (MA) in HF patients, with findings contributing to developing a HF-specific MA assessment scale. Using a cross-sectional, mixed methods design, we conducted an online survey with both closed and open-ended questions distributed to cardiac healthcare providers, working at the National University Hospital in Iceland. The survey consisted of 103 questions divided into 18 themes. Analysis included descriptive statistics of the participants' responses to closed responses with simplified scoring. Free-text responses were grouped into thematic categories and then into subthemes. Of 104 healthcare providers invited, 73 (70%) participated. Key factors identified as most beneficial for supporting MA included supportive patient-provider relationships (97%), selecting suitable drug formulation (96%), healthcare support at home (95%), and multi-dose dispensing from pharmacies (93%). The youngest and oldest HF patients were believed to be at the highest risk of medication non-adherence, particularly among males. Other patients estimated at increased risk included those with alcohol and/or substance abuse (89%), those with limited knowledge of medication effects (89%), those perceiving medication as useless (88%), and those with cognitive impairment (86%). Most participants (73%) agreed that healthcare providers should assess and document MA in clinical care. These findings provide a comprehensive overview of factors that cardiac healthcare providers believe influence non-adherence in HF patients, contributing to the development of a HF-specific MA scale.

Abstract Introduction Amiodarone causes hypothyroidism in 12-25% of treated patients, depending on the classification of hypothyroidism. Amiodarone induced thyrotoxicosis is seen in 1.2%-12%. It is recommended to taper thyroid supplementation after discontinuing amiodarone. Purpose To investigate the prevalence of amiodarone induced thyroid dysfunction in Iceland and the effects of dosage and treatment duration. Design The study population comprised of all patients that were subscribed amiodarone in Iceland during the calendar year of 2014, a total of 1054 patients. Ten patients that never took amiodarone were excluded and there was missing data in 22. Hypothyroidism had been diagnosed in 91 patients before starting amiodarone and 59 took amiodarone for less than 90 days and were excluded from further analysis, leaving 871 patients. Follow up data was obtained from the national health care records both retrospectively and prospectively for first prescription of amiodarone and signs of thyroid related problems. Amiodarone induced hypothyroidism was defined as a raised TSH more than 90 days after starting treatment and further classified into subclinical (with normal T4) and overt (low T4). Amiodarone induced thyrotoxicosis was defined as low TSH with an elevated T4. Results Amiodarone induced hypothyroidism was seen in 22.2% of patients at a mean age of 74 years. 10.7% had overt AIH and 11.6% had subclinical hypothyroidism. Hypothyroidism occurred on average after 3.3 ±0.4 years of treatment. The incidence increased with treatment duration and peaked at 41.8% after 15 years of treatment. The risk did not change with dosage. Only 4.6% on thyroid supplementation therapy had stopped treatment after a mean follow-up of 4.5 years after discontinuing amiodarone. Amiodarone induced thyrotoxicosis was seen in 10.0% with a mean age of 65.6 years. The mean duration of treatment at diagnosis of thyrotoxicosis was 3.9 ±0.6 years. The cumulative risk of thyrotoxicosis was highest (9.9%) during years 3 to 5 but persisted with ongoing treatment and peaked at 17.6% after 13 years of treatment. Higher dosage of amiodarone increased the risk in a dose dependent manner. It was 5% with <200 mg, 11.8% with 200 mg and 14.1% with >200mg (p<0.01). Hospital admission due to thyrotoxicosis was required in 35.3% of patients, 8.8% had thyroidectomies, 2.0% died and 26.5% had hypothyroidism following thyrotoxicosis. 48% were treated with carbimazole, of them 2.0% suffered agranulocytosis, 4.1% had hepatitis and 4.1% had pancreatitis. Conclusion In this nationwide study we found that long term users of amiodarone are at a higher risk of amiodarone induced hypothyroidism or thyrotoxicosis than previously described. Thyroid supplementation treatment is rarely stopped despite the pro-arrhythmic risk of overtreating hypothyroid patients. The high incidence of thyroid related adverse effects is a reminder of the serious side effects of amiodarone treatment.Amiodarone induced hypothyroidismAmiodarone induced Thyrotoxicosis

Non-Cardiac Chest Pain (NCCP) is persistent chest pain in the absence of identifiable cardiac pathology. Some NCCP cases meet criteria for Persistent Physical Symptoms (PPS), where the symptoms are both persistent and distressing/disabling. This study aimed to identify patients that might need specialist treatment for PPS by examining cases of NCCP that meet PPS criteria. We analysed data from 285 chest pain patients that had received an NCCP diagnosis after attending an emergency cardiac department. We compared NCCP patients who did and did not meet the additional criteria for heart-related PPS and hypothesised that the groups would differ in terms of psychological variables and workability. We determined that NCCP patients who meet PPS criteria were more likely than other NCCP patients to be inactive or unable to work, reported more general anxiety and anxiety about their health, were more depressed, ruminated more, and, importantly, had a higher number of other PPS. A high proportion of NCCP patients meet PPS criteria, and they are similar to other PPS patients in terms of comorbidity and disability. This highlights the importance of focusing psychological interventions for this subgroup on the interplay between the range of physical and psychological symptoms present.

Objective. To evaluate the impact of sex on treatment and survival after acute myocardial infarction (AMI) in Iceland. Methods. A retrospective, nationwide cohort study of patients with STEMI (2008-2018) and NSTEMI (2013-2018) and obstructive coronary artery disease. Patient and procedural information were obtained from a registry and electronic health records. Survival was estimated with Kaplan-Meier method and Cox regression analysis used to identify risk factors for long-term mortality. Excess mortality from the AMI episode was estimated by comparing the survival with age- and sex-matched population in Iceland at 30-day interval. Results. A total of 1345 STEMI-patients (24% women) and 1249 NSTEMI-patients (24% women) were evaluated. Women with STEMI (mean age: 71 +/- 11 vs. 67 +/- 12) and NSTEMI (mean age: 69 +/- 13 vs. 62 +/- 12) were older and less likely to have previous cardiovascular disease. There was neither sex difference in the extent of coronary artery disease nor treatment. Although crude one-year post-STEMI survival was lower for women (88.7% vs. 93.4%, p = .006), female sex was not an independent risk factor after adjusting for age and co-morbidities after STEMI and was protective for NSTEMI (HR 0.67, 95% CI: 0.46-0.97). There was excess 30-day mortality in both STEMI and NSTEMI for women compared with sex-, age- and inclusion year-matched Icelandic population, but thereafter the mortality rate was similar. Conclusion. Women and men with AMI in Iceland receive comparable treatment including revascularization and long-term survival appears similar. Prognosis after NSTEMI is better in women, whereas higher early mortality after STEMI may be caused by delays in presentation and diagnosis.

Background and aims: Coronary artery calcium (CAC) and carotid plaque are markers of atherosclerosis and predict future coronary heart disease (CHD) events. The aim of this study was to investigate associations between CAC and carotid plaque in asymptomatic individuals, also in relation to predicted CHD-risk and incident events. A secondary aim was to compare predictive value between CAC, carotid plaque, and total carotid plaque area (TPA) as predictors for future CHD-events.Methods: The REFINE-Reykjavik study is prospective and population-based with CAC-scoring and carotid plaque ultrasound assessment, both presence and area. A total of 948 individuals without clinical CHD were included in the study. CAC scores were categorized into 0,1-100,101-300 and > 300, and carotid plaque into none, minimal and significant. Three models were applied adjusted for age, sex, and each of the Framingham risk score (FRS), local CHD risk score and established CHD risk factors.Results: Combined carotid plaque-and CAC-presence was highly prevalent, 69.5% for males and 41.7% for females (54.5% overall). TPA outperformed base models in CHD prediction, resulting in statistically significant area under the receiver operator characteristic curve (AUC) increase ranging from 0.02 to 0.05. Most CHD-events in females occurred in individuals classified as low-risk with respect to traditional risk factors but with a gradient in observed risk across carotid plaque categories.Conclusions: Carotid plaque was strongly associated with the presence and extent of CAC in asymptomatic individuals in a population-based cohort. Carotid plaque predicts incident CHD events over risk scores and may be useful for refined risk prediction in females.

BACKGROUND: The incidence of diabetes is growing, and diabetics have increased risk of atherosclerosis and diffuse coronary artery disease (CAD). Our aim was to assess the revascularization treatment of diabetics with CAD in Iceland from 2010-2020, changes in management and long-term survival of patients. METHODS: All patients in Iceland with diabetes and CAD on cardiac catheterization 2010-2020 were included in this retrospective, population-based study. We analyzed data from the SCAAR/SWEDEHEART database: patients' background information, findings of cardiac catheterization, planned treatment and results. The Kaplan-Meier method was used to estimate long-term survival and Cox-regression-analysis to adjust for predictor variables. RESULTS: Of 1905 cases (1485 patients), 1230 (65%) underwent PCI, 274 (14%) CABG and 401 (21%) had medical therapy only. The age distribution differed: The PCI group had the widest age bracket, the CABG group the narrowest, and the medical therapy group had the highest mean age. Most patients with STEMI or cardiogenic shock underwent PCI, while most patients with concomitant heart-valve disease underwent CABG. The proportion of patients undergoing CABG increased with more diffuse CAD. 41% of patients with left main-and three-vessel disease underwent CABG while only 2% of those with single-vessel disease. From 2010-2020 the proportion of patients that underwent PCI increased from 49% to 72%. There was no difference in survival between the PCI and CABG groups (p=1.00). CONCLUSION: Three quarters of patients with diabetes and obstructive CAD are now treated with PCI. The PCI and CABG groups had overall equal survival but the groups had different characteristics.

INTRODUCTION:Educational attainment is related to improved health and longevity. We investigated the relationship between educational attainment and cardiovascular risk factors, subclinical atherosclerosis, and incidence of coronary artery disease.MATERIAL AND METHODS:The Reykjavik REFINE study is a population-based study recruiting 6616 subjects, 25-69 years of age from the greater Reykjavik area in 2005-2011. Baseline measurements of cardiovascular risk factors were performed, and all participants had a carotid ultrasound examination to detect subclinical atherosclerotic lesions. Clinical follow-up of cardiovascular disease during a ten-year period was performed. Educational attainment was related to clinical outcome measures.RESULTS:The study population comprised of 3251 men and 3365 women. The proportion of the study population with primary school education only was 20.1%, 31.2% had vocational training, 12.3% had high school education and 36.4% were university graduates. Traditional cardiovascular risk factors were generally higher among subjects with primary school education only. Compared to subjects with university education, the odds ratio of having severe atherosclerotic plaque was 1.84 (95% CI 1.40-2.43) among those with primary school education only and 1.49 (95% CI 1.16-1.91) among subjects with vocational training. The subjects with high school or university education were less likely to develop significant cardiovascular disease during the 10-year follow-up period.CONCLUSION:Primary school and vocational training compared to university education are associated with risk factors of atherosclerotic disease, subclinical carotid plaque, and incidence of cardiovascular disease. The reason for this disparity remains to be clarified but socioeconomic inequality related to less educational attainment might be involved.

Introduction: Coronary artery bypass surgery (CABG) has been standard treatment for patients with left main coronary artery disease (LMCAD) but percutaneous coronary intervention (PCI) can be a good alternative. Our aim was to evaluate revascularization of LMCAD-patients in Iceland and treatment changes in recent years. We also assessed the impact of patient background factors on treatment choice and long-term survival. Methods: This retrospective, population-based registry-study analyzed data from the SCAAR-SWEDEHEART database. Patients with significant LMCAD on coronary angiography in Iceland 2010-2020, without previous history of CABG or contraindication for surgery were enrolled. The Kaplan-Meier method was used to study long-term survival and COX-regression analysis to adjust for predictor variables. Findings: Of 702 LMCAD patients, 195 were treated with PCI, 460 with CABG and 47 with medical therapy. The widest age-range was in the PCI group and the mean age was highest in the medical therapy group. Patients with LMCAD and concomitant three vessel disease or heart valve disese were mostly treated with CABG (76.1% and 84.4%). The majority of patients with LMCAD only were treated with PCI, as well as patients presenting with STEMI or in cardiogenic shock (67.1% and 70.0%). The proportion of patients treated with PCI increased from 19.8% in 2010-2015 to 42.7% in 2016-2020. There was no significant difference in survival between the PCI and CABG-groups (p=0.41). Conclusions: In patients with LMCAD the main factors determining treatment choice are age, anatomical complexity and acuteness. There has been a significant increase in LMCAD patients treated with PCI.

INTRODUCTION:The incidence of acute myocardial infarction (AMI) might not be decreasing as much among young adults as in the general population in recent years. The goal of our study was to explore incidence, risk factors and prognosis of AMI among young patients in Iceland. MATERIAL AND METHODS:This was a retrospective case control study. The data was obtained from the SCAAR-SWEDEHEART database, medical records from Landspitali University Hospital and the death register from the Directorate of Health. The epidemiology of women ≤55 years and men ≤50 years diagnosed with AMI (STEMI/NSTEMI) in Iceland in 2014-2020 was compared with older patients. RESULTS:Of all the cases (2852), 344 patients (12%) were young. No change was demonstrated in the incidence of AMI in the young patients during the study period. The proportion of STEMI was higher among young patients (52% vs. 35%, p<0.001). Smoking (50% vs. 26%, p<0.001) and obesity (BMI>30 kg/m2)(47% vs. 36%, p<0.01) were more prevalent in younger patiens compared to the older. Older patients were more likely to die in the year following the AMI, both from all-cause (7% vs. 3%, p<0.05) and cardiovascular mortality (7% vs. 3%, p<0.05). A difference in recurrent AMI between the young and older patients was not demonstrated (2% vs. 3%, p=0.3). CONCLUSION:During the research period, a change in the incidence of AMI among young patients, was not demonstrated. Younger patients with AMI have different risk factors than older patients, they have lower mortality rate but the same risk of recurrent AMI.

Background: Loss-of-function mutations in the LDL (low-density lipoprotein) receptor gene ( LDLR ) cause elevated levels of LDL cholesterol and premature cardiovascular disease. To date, a gain-of-function mutation in LDLR with a large effect on LDL cholesterol levels has not been described. Here, we searched for sequence variants in LDLR that have a large effect on LDL cholesterol levels. Methods: We analyzed whole-genome sequencing data from 43 202 Icelanders. Single-nucleotide polymorphisms and structural variants including deletions, insertions, and duplications were genotyped using whole-genome sequencing-based data. LDL cholesterol associations were carried out in a sample of >100 000 Icelanders with genetic information (imputed or whole-genome sequencing). Molecular analyses were performed using RNA sequencing and protein expression assays in Epstein-Barr virus-transformed lymphocytes. Results: We discovered a 2.5-kb deletion (del2.5) overlapping the 3′ untranslated region of LDLR in 7 heterozygous carriers from a single family. Mean level of LDL cholesterol was 74% lower in del2.5 carriers than in 101 851 noncarriers, a difference of 2.48 mmol/L (96 mg/dL; P =8.4×10 − 8 ). Del2.5 results in production of an alternative mRNA isoform with a truncated 3′ untranslated region. The truncation leads to a loss of target sites for microRNAs known to repress translation of LDLR . In Epstein-Barr virus-transformed lymphocytes derived from del2.5 carriers, expression of alternative mRNA isoform was 1.84-fold higher than the wild-type isoform ( P =0.0013), and there was 1.79-fold higher surface expression of the LDL receptor than in noncarriers ( P =0.0086). We did not find a highly penetrant detrimental impact of lifelong very low levels of LDL cholesterol due to del2.5 on health of the carriers. Conclusions: Del2.5 is the first reported gain-of-function mutation in LDLR causing a large reduction in LDL cholesterol. These data point to a role for alternative polyadenylation of LDLR mRNA as a potent regulator of LDL receptor expression in humans.

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.

Background Patients undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy and some require additional anticoagulation. We aimed to investigate the incidence of acute gastrointestinal bleeding (AGIB) among PCI patients receiving antiplatelet and anticoagulant therapy. Methods A population-based study that included all patients undergoing PCI during 2008-2016 in Iceland. Data from the Icelandic Medicines Registry were obtained on all outpatient prescriptions 1 year after first PCI. Patients receiving single or dual-antiplatelet therapy with or without anticoagulation cotherapy were analyzed. Rehospitalization for AGIB and endoscopic data were obtained within the 12-month follow-up period. Results A total of 5166 patients (male 75%) underwent PCI during the study period. The incidence of AGIB was 1% (54/5166) per year. The mean age among non-bleeders 65 (+/- 11) years was lower than among bleeders 69 (+/- 9) years (p = .002). The proportion of acute upper GIB (AUGIB) was 56%, whereas lower GIB occurred in 44%. Overall, 41% with AUGIB had PPIs compared to 39% of non-bleeders (NS). The incidence of AGIB among patients on single antiplatelet therapy combined with an anticoagulant was 2.5% compared to 0.9% among those on single antiplatelet treatment alone (p = .028). The number needed to harm (NNH) for treatment with single antiplatelet therapy and anticoagulant therapy compared to single antiplatelet therapy was 62 but no deaths related to AGIB. Conclusions The 1-year incidence of AGIB was low with no mortality. Bleeding risk was found to be higher among patients on single antiplatelet therapy combined with anticoagulant therapy compared to patients on single antiplatelet therapy alone.

BACKGROUND:Elevated copeptin, a marker for vasopressin release, has been associated with impaired prognosis in acute myocardial infarction (MI). The aim was to investigate whether this association extends beyond the acute phase and whether it is related to markers of stress (cortisol) and heart failure (NTproBNP).METHODS:Copeptin, cortisol and NTproBNP were measured in 926 participants (age: 76.0; male: 48.5%) in the ICELAND MI study whereof 246 had a previous MI (91 recognizable (RMI) and 155 previously unrecognizable (UMI) detected by cardiac magnetic resonance imaging). The primary endpoint was cardiovascular events (CVEs), and secondary endpoints were total mortality, heart failure and MI (median follow-up was 9.1 years). The relation between copeptin and prognosis was assessed with the Cox proportional hazard regression (unadjusted, adjusted for cortisol and NTproBNP, respectively, and a multiple model: copeptin, cortisol, NTproBNP, age, sex, serum creatinine, heart failure).RESULTS:Copeptin was higher in participants with MI (8.9 vs. 6.4 pmol/L; P < .01), with no difference between RMI vs. UMI. Increased copeptin correlated with evening cortisol (r = .11; P < .01) and NTproBNP (r = .07; P = .04). Copeptin was associated with CVE and total mortality after adjusting for cortisol and NTproBNP separately, and remained significantly associated with total mortality in the multiple model.CONCLUSIONS:Copeptin was higher in subjects with previous MI regardless whether previously recognized or not. Copeptin correlated weakly with cortisol and NTproBNP, and was independently associated with total mortality. This indicates that the prognostic implications of copeptin are not only mediated by heart failure or stress, supporting the assumption that copeptin is a marker of general vulnerability.