Low-density lipoprotein cholesterol response to statins according to comorbidities and co-medications: A population-based study.

BACKGROUND: The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients. METHODS: This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (P-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations. RESULTS: Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance. CONCLUSION: Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin.

Vascular health years after a hypertensive disorder of pregnancy: The EPOCH study.

BACKGROUND: Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum. METHODS: Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound. RESULTS: Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses, cases (N = 68) were more likely than controls (N = 71) to have hypertension (18% vs 4%, P = .034), higher calculated ASCVD risk (0.6 vs 0.4, P = .02), higher blood pressures (systolic: 118.5 vs 111.6 mm Hg, P = .0004; diastolic: 75.2 vs 69.8 mm Hg, P = .0004), and higher augmentation index values (7.7 vs 2.3, P = .03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs 0.5, P = .29) or reactive hyperemia index (2.1 vs 2.1, P = .93), nor in pulse wave amplitude (416 vs 326, P = .11), carotid elastic modulus (445 vs 426, P = .36), or carotid beta stiffness (2.8 vs 2.8, P = .86). CONCLUSION: Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis.

Prevalence of frequent premature ventricular contractions and nonsustained ventricular tachycardia in older women screened for atrial fibrillation in the Women's Health Initiative.

BACKGROUND: Frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) have been associated with cardiovascular disease and mortality. Their prevalence, especially in ambulatory populations, is understudied and limited by few female participants and the use of short-duration (24- to 48-hour) monitoring. OBJECTIVE: The objective of this study was to report the prevalence of frequent PVCs and NSVT in a community-based population of women likely to undergo electrocardiogram (ECG) screening by sequential patch monitoring. METHODS: Participants from the Women's Health Initiative Strong and Healthy (WHISH) trial with no history of atrial fibrillation (AF) but 5-year predicted risk of incident AF ≥5% by CHARGE-AF score were randomly selected to undergo screening with 7-day ECG patch monitors at baseline, 6 months, and 12 months. Recordings were reviewed for PVCs and NSVT (>5 beats); data were analyzed with multivariate regression models. RESULTS: There were 1067 participants who underwent ECG screening at baseline, 866 at 6 months, and 777 at 12 months. Frequent PVCs were found on at least 1 patch from 4.3% of participants, and 1 or more episodes of NSVT were found in 12 (1.1%) women. PVC frequency directly correlated with CHARGE-AF score and NSVT on any patch. Detection of frequent PVCs increased with sequential monitoring. CONCLUSION: In postmenopausal women at high risk for AF, frequent PVCs were relatively common (4.3%) and correlated with higher CHARGE-AF score. As strategies for AF screening continue to evolve, particularly in those individuals at high risk of AF, the prevalence of incidental ventricular arrhythmias is an important benchmark to guide clinical decision-making.

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. METHODS: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

Derivation and validation of a novel functional FFRCT score incorporating the burden of coronary stenosis severity and flow impairment to predict clinical events.

BACKGROUND: A score combining the burden of stenosis severity on coronary computed tomography angiography (CCTA) and flow impairment by fractional flow reserve derived from computed tomography (FFRCT) may be a better predictor of clinical events than either parameter alone. METHODS: The Functional FFRCT Score (FFS) combines CCTA and FFRCT parameters in an allocated point-based system. The feasibility of the FFS was assessed in cohort of 72 stable chest pain patients with matched CCTA and FFRCT datasets. Validation was performed using 2 cohorts: (a) 4468 patients from the ADVANCE Registry to define its association with revascularization and major adverse cardiovascular events (MACE); (b) 212 patients from the FORECAST trial to determine predictors of MACE. RESULTS: The median calculation time for the FFS was 10 (interquartile range 6-17) seconds, with strong intra-operator and inter-operator agreement (Cohen's Kappa 0.89 (±0.37, p â€‹< â€‹0.001) and 0.83 (±0.04, p â€‹< â€‹0.001, respectively). The FFS correlated strongly with both the CT-SYNTAX and the Functional CT-SYNTAX scores (rS â€‹= â€‹0.808 for both, p â€‹< â€‹0.001). In the ADVANCE cohort the FFS had good discriminatory abilities for revascularization with an area under the curve of 0.82, 95 â€‹% confidence interval (CI) 0.81-0.84, p â€‹< â€‹0.001. Patients in the highest FFS tertile had significantly higher rates of revascularization (61 â€‹% vs 5 â€‹%, p â€‹< â€‹0.001) and MACE (1.9 â€‹% vs 0.5 â€‹%, p â€‹= â€‹0.001) compared with the lowest FFS tertile. In the FORECAST cohort the FFS was an independent predictor of MACE at 9-month follow-up (hazard ratio 1.04, 95 â€‹% CI 1.01-1.08, p â€‹< â€‹0.01). CONCLUSION: The FFS is a quick-to-calculate and reproducible score, associated with revascularization and MACE in two distinct populations of stable symptomatic patients.

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. METHODS: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Myocardial microstructure assessed by T1 mapping after on-pump and off-pump coronary artery bypass grafting.

Background: The correlation between the release of cardiac biomarkers after revascularization, in the absence of late gadolinium enhancement (LGE) or myocardial edema, and the development of myocardial tissue damage remains unclear. This study sought to identify whether the release of biomarkers is associated with cardiac damage by assessing myocardial microstructure on T1 mapping after on-pump (ONCAB) and off-pump coronary artery bypass grafting (OPCAB). Methods: Seventy-six patients with stable multivessel coronary artery disease (CAD) and preserved systolic ventricular function were included. T1 mapping, high-sensitive cardiac troponin I (cTnI), creatine kinase myocardial band (CK-MB) mass, and ventricular dimensions and function were measured before and after procedures. Results: Of the 76 patients, 44 underwent OPCAB, and 32 ONCAB; 52 were men (68.4%), and the mean age was 63±8.5 years. In both OPCAB and ONCAB the native T1 values were similar before and after surgeries. An increase in extracellular volume (ECV) values after the procedures was observed, due to the decrease in hematocrit levels during the second cardiac resonance. However, the lambda partition coefficient showed no significant difference after the surgeries. The median peak release of cTnI and CK-MB were higher after ONCAB than after OPCAB [3.55 (2.12-4.9) vs. 2.19 (0.69-3.4) ng/mL, P=0.009 and 28.7 (18.2-55.4) vs. 14.3 (9.3-29.2) ng/mL, P=0.009, respectively]. Left ventricular ejection fraction (LVEF) was similar in both groups before and after surgery. Conclusions: In the absence of documented myocardial infarction, T1 mapping did not identify structural tissue damage after surgical revascularization with or without cardiopulmonary bypass (CPB), despite the excessive release of cardiac biomarkers.

Association Between Age and Low-Density Lipoprotein Cholesterol Response to Statins : A Danish Nationwide Cohort Study.

BACKGROUND: There is large patient-to-patient variability in the low-density lipoprotein cholesterol (LDL-C) response to statin treatment. The reduction in LDL-C may depend on the age of the patient treated-particularly in older adults, who have been substantially underrepresented in randomized controlled trials. OBJECTIVE: To investigate the association between age and the LDL-C reduction by statins. DESIGN: Nationwide, register-based cohort study. SETTING: Denmark, 2008 to 2018. PARTICIPANTS: 82 958 simvastatin or atorvastatin initiators with LDL-C measurements before and during statin use. MEASUREMENTS: Statin response, defined as percentage reduction in prestatin LDL-C level, and percentage reduction differences (PRDs) according to age and simvastatin or atorvastatin dose based on a longitudinal model for LDL-C. RESULTS: Among 82 958 statin initiators, 10 388 (13%) were aged 75 years or older. With low- to moderate-intensity statins, initiators aged 75 years or older had greater mean LDL-C percentage reductions than initiators younger than 50 years-for example, 39.0% versus 33.8% for simvastatin, 20 mg, and 44.2% versus 40.2% for atorvastatin, 20 mg. The adjusted PRD for initiators aged 75 years compared with initiators aged 50 years was 2.62 percentage points. This association was consistent for primary prevention (2.54 percentage points) and secondary prevention (2.32 percentage points) but smaller for initiators of high-intensity statins (atorvastatin, 40 mg: 1.36 percentage points; atorvastatin, 80 mg: -0.58 percentage point). LIMITATION: Use of administrative data, observational pre-post comparison with a moderately high proportion of missing data, lack of information on body mass index, and the mainly White study population may limit generalizability. CONCLUSION: Low- to moderate-intensity statins were associated with a greater reduction in LDL-C levels in older persons than younger persons and may be more appealing as initial treatment in older adults who are at increased risk for adverse events. PRIMARY FUNDING SOURCE: The Independent Research Fund Denmark, Brødrene Hartmanns Fond, and Fonden til Lægevidenskabens Fremme.

Evaluation of the association between circulating IL-1ß and other inflammatory cytokines and incident atrial fibrillation in a cohort of postmenopausal women.

BACKGROUND: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1ß, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF. METHODS: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, education, hypertension, diabetes, hyperlipidemia, current smoking, and history of coronary heart disease, congestive heart failure, or peripheral artery disease. RESULTS: Of 16,729 women, 3,943 developed AF over an average of 8.5 years. Racial and ethnic groups included White (77.4%), Black/African-American (16.1%), Asian (2.7%), American Indian/Alaska Native (1.0%), and Hispanic (5.5%). Baseline IL-1ß log continuous levels were not significantly associated with incident AF (HR 0.86 per 1 log [pg/mL] increase, P= .24), similar to those of other inflammatory cytokines, IL-7, IL-8, IL-10, IGF-1, and TNF-α. There were significant associations between C-reactive protein (CRP) and IL-6 with incident AF. CONCLUSIONS: In this large cohort of postmenopausal women, there was no significant association between IL-1ß and incident AF, although downstream effectors, CRP and IL-6, were associated with incident AF.

Randomized comparison of chest pain evaluation with FFRCT or standard care: Factors determining US costs.

BACKGROUND: FFRCT assesses the functional significance of lesions seen on CTCA, and may be a more efficient approach to chest pain evaluation. The FORECAST randomized trial found no significant difference in costs within the UK National Health Service, but implications for US costs are unknown. The purpose of this study was to compare costs in the FORECAST trial based on US healthcare cost weights, and to evaluate factors affecting costs. METHODS: Patients with stable chest pain were randomized either to the experimental strategy (CTCA with selective FFRCT), or to standard clinical pathways. Pre-randomization, the treating clinician declared the planned initial test. The primary outcome was nine-month cardiovascular care costs. RESULTS: Planned initial tests were CTCA in 912 patients (65%), stress testing in 393 (28%), and invasive angiography in 94 (7%). Mean US costs did not differ overall between the experimental strategy and standard care (cost difference +7% (+$324), CI -12% to +26%, p â€‹= â€‹0.49). Costs were 4% lower with the experimental strategy in the planned invasive angiography stratum (p for interaction â€‹= â€‹0.66). Baseline factors independently associated with costs were older age (+43%), male sex (+55%), diabetes (+37%), hypertension (+61%), hyperlipidemia (+94%), prior angina (+24%), and planned invasive angiography (+160%). Post-randomization cost drivers were coronary revascularization (+348%), invasive angiography (267%), and number of tests (+35%). CONCLUSIONS: Initial evaluation of chest pain using CTCA with FFRCT had similar US costs as standard care pathways. Costs were increased by baseline coronary risk factors and planned invasive angiography, and post-randomization invasive procedures and the number of tests. Registration at ClinicalTrials.gov (NCT03187639).

Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo.

Importance: Statin-associated muscle symptoms (SAMS) are common and may lead to discontinuation of indicated statin therapy. Observational studies suggest that vitamin D therapy is associated with reduced statin intolerance, but no randomized studies have been reported. Objective: To test whether vitamin D supplementation was associated with prevention of SAMS and a reduction of statin discontinuation. Design, Setting, and Participants: Men 50 years or older and women 55 years or older, free of cancer and cardiovascular disease, were enrolled in a randomized, placebo-controlled, double-blind clinical trial of vitamin D supplementation. Participants who initiated statin therapy after randomization were surveyed in early 2016. The data were analyzed in early 2022. Interventions: Daily cholecalciferol (2000 international units) or placebo with assessment of statin prescriptions during follow-up. Main Outcomes and Measures: Muscle pain or discomfort lasting several days (primary outcome) and discontinuation of a statin due to SAMS (secondary outcome). Results: Statins were initiated by 1033 vitamin D-assigned participants and 1050 placebo-assigned participants; mean (SD) age was 66.8 (6.2) years and 49% were women. Over 4.8 years of follow-up, SAMS were reported by 317 participants (31%) assigned vitamin D and 325 assigned placebo (31%). The adjusted odds ratio (OR) was 0.97 (95% CI, 0.80-1.18; P = .78). Statins were discontinued by 137 participants (13%) assigned to vitamin D and 133 assigned to placebo (13%) with an adjusted OR of 1.04 (95% CI, 0.80-1.35; P = .78). These results were consistent across pretreatment 25-hydroxy vitamin D levels (interaction P value = .83). Among participants with levels less than 20 ng/mL, SAMS were reported by 28 of 85 vitamin D-assigned participants (33%) and 33 of 95 placebo-assigned participants (35%). For those with levels less than 30 ng/ml, SAMS were reported by 88 of 330 vitamin-D assigned participants (27%) and 96 of 323 of placebo-assigned participants (30%). Conclusions and Relevance: Vitamin D supplementation did not prevent SAMS or reduce statin discontinuation. These results were consistent across pretreatment 25-hydroxy vitamin D levels. Trial Registration: ClinicalTrials.gov Identifier: NCT01169259.

Men who live alone have worse anticoagulation control: A Danish registry study.

Men living alone may have particular difficulty in managing chronic medical conditions. Anticoagulation control, a sensitive indicator of self-management, was significantly worse among men living alone.

Serial 7-Day Electrocardiogram Patch Screening for AF in High-Risk Older Women by the CHARGE-AF Score.

BACKGROUND: Asymptomatic atrial fibrillation (AF) is associated with an increased risk of stroke. The yield of serial electrocardiographic (ECG) screening for AF is unknown. OBJECTIVES: The aim of this study was to determine the frequency of AF detected by serial, 7-day ECG patch screenings in older women identified as having an elevated risk of AF according to the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology)-AF clinical prediction score. METHODS: Postmenopausal women with a 5-year predicted risk of new-onset AF ≥5% according to CHARGE-AF were recruited from the ongoing WHISH (Women's Health Initiative Strong and Healthy) randomized trial of a physical activity intervention. Participants with AF at baseline by self-report or medical records review were excluded. Screening with 7-day ECG patch monitors was performed at baseline, 6 months, and 12 months from study enrollment. RESULTS: On baseline monitoring, 2.5% of the cohort had AF detected, increasing to 3.7% by 6 months and 4.9% cumulatively by 12 months. Yield of patch screening was higher among participants with a higher (≥10%) CHARGE-AF score: 4.2% had AF detected at baseline, 5.9% at 6 months, and 7.2% at 12 months. Most participants with patch-identified AF never had a clinical diagnosis of AF (36 of 46 [78%]). CONCLUSIONS: Older women with an elevated CHARGE-AF score had a high prevalence of AF on 7-day ECG patch screening. Serial screening over 12 months substantially increased the detection of AF. These data can be useful in helping identify high-risk participants for enrollment in future studies of the management of asymptomatic AF.(Women's Health Initiative Silent Atrial Fibrillation Recording Study [WHISH STAR]; NCT05366803.).

Statin-associated muscle symptoms in the VITamin D and OmegA-3 TriaL (VITAL).

Statins are highly effective medications that reduce risk of atherosclerotic cardiovascular disease, but are very commonly discontinued by patients because of muscle symptoms. The risk factors for statin-associated muscle symptoms (SAMS) are not well understood, so in this study we examined the predictors of SAMS in a well-studied cohort of patients in the VITAL trial. We found that female sex and younger age (50-64 years) were significant, independent predictors of higher rates of SAMS.

Familial Resemblance in Low-Density Lipoprotein Cholesterol Response to Statins in the Danish Population.

Background Change in low-density lipoprotein cholesterol (LDL-C) level after statin initiation varies widely among individuals, and in part may be because of factors shared by family members. Methods and Results We used the Danish national registers to identify 89 006 individuals who initiated statins between 2008 and 2018 and had LDL-C measured immediately before and after the start of treatment. Among these, we identified 5148 first-degree relatives and 3198 spouses. We decomposed the variation in attained LDL-C level after statin initiation by applying a mixed-effect model with 5 variance components (inter-family and inter-individual variance in pre-statin LDL-C level, inter-family and inter-individual variance in statin response, and residual variance). Results were presented as a percentage of the total variance explained by the different variance components. We found that half of the variation in attained LDL-C level after statin initiation consisted of variance in statin response, approximately one third of variance in pre-statin LDL-C level, and the remaining 10% to 15% of residual variance. While the inter-individual variance in statin response accounted for almost half of the LDL-C variation in both cohorts, the inter-family variance in statin response accounted for 3.3% among first-degree relatives and for 6.0% among spouses. Conclusions Individual factors account for most of the variation in LDL-C level after statin initiation; factors affecting statin response common within spouses and first-degree relatives account for a similar share of variation. These results suggest a modest influence of shared genetics and shared familial environment on statin response.

Quality of Life After Fractional Flow Reserve-Guided PCI Compared With Coronary Bypass Surgery.

BACKGROUND: Previous studies have shown that quality of life improves after coronary revascularization more so after coronary artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI). This study aimed to evaluate the effect of fractional flow reserve guidance and current generation, zotarolimus drug-eluting stents on quality of life after PCI compared with CABG. METHODS: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) is a multicenter, international trial including 1500 patients with 3-vessel coronary artery disease who were randomly assigned to either CABG or fractional flow reserve-guided PCI. Quality of life was measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire at baseline and 1 and 12 months. The Canadian Cardiovascular Class angina grade and working status were assessed at the same time points and at 6 months. The primary objective was to compare EQ-5D summary index at 12 months. Secondary end points included angina grade and work status. RESULTS: The EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference, 0.001 [95% CI, -0.016 to 0.017]; P=0.946). The trajectory of EQ-5D during the 12 months differed (P<0.001) between PCI and CABG: at 1 month, EQ-5D was 0.063 (95% CI, 0.047 to 0.079) higher in the PCI group. A similar trajectory was found for the EQ (EuroQol) visual analogue scale. The proportion of patients with Canadian Cardiovascular Class 2 or greater angina at 12 months was 6.2% versus 3.1% (odds ratio, 2.5 [95% CI, 0.96-6.8]), respectively, in the PCI group compared with the CABG group. A greater percentage of younger patients (<65 years old) were working at 12 months in the PCI group compared with the CABG group (68% versus 57%; odds ratio, 3.9 [95% CI, 1.7-8.8]). CONCLUSIONS: In the FAME 3 trial, quality of life after fractional flow reserve-guided PCI with current generation drug-eluting stents compared with CABG was similar at 1 year. The rate of significant angina was low in both groups and not significantly different. The trajectory of improvement in quality of life was significantly better after PCI, as was working status in those <65 years old. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Impact of socioeconomic position on initiation of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes - a Danish nationwide observational study.

BACKGROUND: Low socioeconomic position may affect initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucacon-like-peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D). We examined the association between socioeconomic position and initiation of SGLT-2i or GLP-1RA in patients with T2D at time of first intensification of antidiabetic treatment. METHODS: Through nationwide registers, we identified all Danish patients on metformin who initiated second-line add-on therapy between December 10, 2012, and December 31, 2020. For each time period (2012-2014, 2015-2017, and 2018-2020), we used multivariable multinomial logistic regression to associate disposable income, as proxy for socioeconomic position, with the probability of initiating a specific second-line treatment at time of first intensification. We reported probabilities standardised to the distribution of demographics and comorbidities of patients included in the last period (2018-2020). FINDINGS: We included 48915 patients (median age 62 years; 61·7% men). In each time period, high-income patients were more often men and had less comorbidities as compared with low income-patients. In each time period, the standardised probability of initiating a SGLT-2i or a GLP-1RA was significantly higher in the highest income group compared with the lowest: 11·4% vs. 9·5% (probability ratio [PR] 1·21, 95 % confidence interval [CI] 1·01-1·44) in 2012-2014; 22·6% vs. 19.6% (PR 1·15, CI 1·05-1·27) in 2015-2017; and 65·8% vs. 54·8% (PR 1·20, CI 1·16-1·24) in 2018-2020. The differences by income were consistent across multiple subgroups. INTERPRETATION: Despite a universal healthcare system, low socioeconomic position was consistently associated with a lower probability of initiating a SGLT-2i or a GLP-1RA. These disparities may widen the future socioeconomic gap in cardiovascular outcomes. FUNDING: The work was funded by unrestricted grants from 'Region Sjaelland Den Sundhedsvidenskabelige Forskningsfond' and 'Murermester Lauritz Peter Christensen og hustru Kirsten Sigrid Christensens Fond'.