FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).

Vitamin K1 intake is associated with lower risk for all-cause and cardiovascular disease mortality in community-dwelling older Australian women.

BACKGROUND AND AIMS: Assessing the relationship between vitamin K1 intakes, using region-specific food databases, with both all-cause, and cardiovascular disease (CVD) mortality warrants further investigation to inform future preventative strategies. Consequently, we examined the aforementioned associations in the Perth Longitudinal Study of Ageing Women (PLSAW). METHODS AND RESULTS: 1436 community-dwelling older Australian women (mean ± SD age 75.2 ± 2.7 years) completed a validated food frequency questionnaire at baseline (1998). Vitamin K1 intake was calculated based on an Australian vitamin K food database, supplemented with published data. All-cause and CVD mortality data was obtained from linked health records. Associations were examined using restricted cubic splines within Cox-proportional hazard models, adjusted for a range of cardiovascular and lifestyle related risk factors. Over 15 years of follow-up, 601 (41.9%) women died, with 236 deaths (16.4%) due to CVD. Compared to women with the lowest vitamin K1 intakes (Quartile 1, median 49.1 µg/day), those with the highest intakes (Quartile 4, median 119.3 µg/day) had lower relative hazards for all-cause mortality (HR 0.66 95%CI 0.51-0.86) and CVD mortality (HR 0.61 95%CI 0.41-0.92). A plateau in the inverse association was observed from vitamin K1 intakes of approximately ≥80 µg/day. CONCLUSION: Higher vitamin K1 intakes were associated with lower risk for both all-cause and CVD mortality in community-dwelling older women, independent of CVD related risk factors. A higher intake of vitamin K1 rich foods, such as leafy green vegetables, may support cardiovascular health.

Dietary Vitamin K1 Intake and Incident Aortic Valve Stenosis.

BACKGROUND: Leaflet calcification contributes to the development and progression of aortic valve stenosis. Vitamin K activates inhibitors of vascular calcification and may modulate inflammation and skeletal bone loss. Therefore, we aimed to determine whether higher dietary intakes of vitamin K1 are associated with a lower incidence of aortic stenosis. METHODS: In the Danish Diet, Cancer and Health study, participants aged 50 to 64 years completed a 192-item food frequency questionnaire at baseline, from which habitual intakes of vitamin K1 were estimated. Participants were prospectively followed using linkage to nationwide registers to determine incident aortic valve stenosis (primary outcome) and aortic stenosis with subsequent complications (aortic valve replacement, heart failure, or cardiovascular disease-related mortality; secondary outcome). RESULTS: In 55 545 participants who were followed for a maximum of 21.5 years, 1085 were diagnosed with aortic stenosis and 615 were identified as having subsequent complications. Participants in the highest quintile of vitamin K1 intake had a 23% lower risk of aortic stenosis (hazard ratio, 0.77 [95% CI, 0.63-0.94]) and a 27% lower risk of aortic stenosis with subsequent complications (hazard ratio, 0.73 [95% CI, 0.56-0.95]), compared with participants in the lowest quintile after adjusting for demographics and cardiovascular risk factors. CONCLUSIONS: In this study, a high intake of vitamin K1-rich foods was associated with a lower incidence of aortic stenosis and a lower risk of aortic stenosis with subsequent complications.

The 2023 Model Core Content of Disaster Medicine.

INTRODUCTION: Disaster Medicine (DM) is the clinical specialty whose expertise includes the care and management of patients and populations outside conventional care protocols. While traditional standards of care assume the availability of adequate resources, DM practitioners operate in situations where resources are not adequate, necessitating a modification in practice. While prior academic efforts have succeeded in developing a list of core disaster competencies for emergency medicine residency programs, international fellowships, and affiliated health care providers, no official standardized curriculum or consensus has yet been published to date for DM fellowship programs based in the United States. STUDY OBJECTIVE: The objective of this work is to define the core curriculum for DM physician fellowships in the United States, drawing consensus among existing DM fellowship directors. METHODS: A panel of DM experts was created from the members of the Council of Disaster Medicine Fellowship Directors. This council is an independent group of DM fellowship directors in the United States that have met annually at the American College of Emergency Physicians (ACEP)'s Scientific Assembly for the last eight years with meeting support from the Disaster Preparedness and Response Committee. Using a modified Delphi technique, the panel members revised and expanded on the existing Society of Academic Emergency Medicine (SAEM) DM fellowship curriculum, with the final draft being ratified by an anonymous vote. Multiple publications were reviewed during the process to ensure all potential topics were identified. RESULTS: The results of this effort produced the foundational curriculum, the 2023 Model Core Content of Disaster Medicine. CONCLUSION: Members from the Council of Disaster Medicine Fellowship Directors have developed the 2023 Model Core Content for Disaster Medicine in the United States. This living document defines the foundational curriculum for DM fellowships, providing the basis of a standardized experience, contributing to the development of a board-certified subspecialty, and informing fellowship directors and DM practitioners of content and topics that may appear on future certification examinations.

9-1-1 Activations from Ambulatory Care Centers: A Sicker Pediatric Population.

BACKGROUND: Pediatric patients transferred by Emergency Medical Services (EMS) from urgent care (UC) and office-based physician practices to the emergency department (ED) following activation of the 9-1-1 EMS system are an under-studied population with scarce literature regarding outcomes for these children. The objectives of this study were to describe this population, explore EMS level-of-care transport decisions, and examine ED outcomes. METHODS: This was a retrospective review of patients zero to <15 years of age transported by EMS from UC and office-based physician practices to the ED of two pediatric receiving centers from January 2017 through December 2019. Variables included reason for transfer, level of transport, EMS interventions and medications, ED medications/labs/imaging ordered in the first hour, ED procedures, ED disposition, and demographics. Data were analyzed with descriptive statistics, X test, point biserial correlation, two-sample z test, Mann-Whitney U test, and 2-way ANOVA. RESULTS: A total of 450 EMS transports were included in this study: 382 Advanced Life Support (ALS) runs and 68 Basic Life Support (BLS) runs. The median patient age was 2.66 years, 60.9% were male, and 60.7% had private insurance. Overall, 48.9% of patients were transported from an office-based physician practice and 25.1% were transported from UC. Almost one-half (48.7%) of ALS patients received an EMS intervention or medication, as did 4.41% of BLS patients. Respiratory distress was the most common reason for transport (46.9%). Supplemental oxygen was the most common EMS intervention and albuterol was the most administered EMS medication. There was no significant association between level of transport and ED disposition (P = .23). The in-patient admission rate for transported patients was significantly higher than the general ED admission rate (P <.001). CONCLUSION: This study demonstrates that pediatric patients transferred via EMS after activation of the 9-1-1 system from UC and medical offices are more acutely ill than the general pediatric ED population and are likely sicker than the general pediatric EMS population. Paramedics appear to be making appropriate level-of-care transport decisions.

Improved arterial inflammation with high dose omega-3 fatty acids in patients with elevated lipoprotein(a): Selective effect of eicosapentaenoic acid?

Elevated lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease. However, there are no approved and effective treatments for lowering Lp(a) and the associated cardiovascular risks. Omega-3 fatty acids (ω-3FAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have both triglyceride-lowering and anti-inflammatory properties. This pilot study investigated the effect of high dose ω-3FAs (3.6 g/day) on arterial inflammation in 12 patients with elevated Lp(a) (> 0.5 g/L) and stable coronary artery disease (CAD) receiving cholesterol-lowering treatment. Arterial inflammation was determined using 18F-fluorodexoyglucose positron emission tomography/computed tomography before and after 12-weeks intervention. ω-3FAs significantly lowered plasma concentrations of triglycerides (-17%, p < 0.01), Lp(a) (-5%, p < 0.01) as well as aortic maximum standardized uptake value (SUVmax) (-4%, p < 0.05). The reduction in SUVmax was significantly inversely associated with average on-treatment EPA (r = -0.750, p < 0.01), but not DHA and triglyceride, concentrations. In conclusion, high dose ω-3FAs decrease arterial inflammation in patients with elevated Lp(a) and stable CAD, which may involve a direct arterial effect of EPA.

Quantitative aortography for assessment of aortic regurgitation in the era of percutaneous aortic valve replacement.

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries.

Characteristics and Outcomes of Young Patients With ST-Elevation Myocardial Infarction Without Standard Modifiable Risk Factors.

Patients with ST-elevation myocardial infarction (STEMI) with no standard modifiable risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, and smoking) have worse short-term mortality than those with SMuRFs. Whether this association extends to younger patients is unclear. A retrospective cohort study was performed of patients aged 18 to 45 years with STEMI at 3 Australian hospitals between 2010 and 2020. Nonatherosclerotic causes of STEMI were excluded. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 1 and 2-year mortality. Cox proportional hazards analysis was used. Of 597 patients, the median age was 42 (interquartile range 38 to 44) years, 85.1% were men and 8.4% were SMuRF-less. Patients who are SMuRF-less were >2 times more likely to have cardiac arrest (28.0% vs 12.6%, p = 0.003); require vasopressors (16.0% vs 6.8%, p = 0.018), mechanical support (10.0% vs 2.3%, p = 0.046), or intensive care admission (20.0% vs 5.7%, p <0.001); and have higher rate of left anterior descending artery infarcts than those with SMuRFs (62.0% vs 47.2%, p = 0.045). No significant differences in thrombolysis or percutaneous intervention were observed. Guideline-directed medical therapy at discharge was high (>90%), and not different in the SMuRF-less. 30-day mortality was almost fivefold higher in the SMuRF-less (hazard ratio 4.70, 95% confidence interval 1.66 to 13.35, p = 0.004), remaining significant at 1 and 2 years. In conclusion, young patients who are SMuRF-less have a higher 30-day mortality after STEMI than their counterparts with SMuRFs. This may be partially mediated by higher rates of cardiac arrest and left anterior descending artery territory events. These findings further highlight the need for improved prevention and management of SMuRF-less STEMI.

Impact of vascular screening interventions on perceived threat, efficacy beliefs and behavioural intentions: a systematic narrative review.

Health-related behaviours contribute to the global burden of cardiovascular disease (CVD). Cardiovascular imaging can be used to screen asymptomatic individuals for increased risk of CVD to enable earlier interventions to promote health-related behaviours to prevent or reduce CVD risk. Some theories of behaviour and behaviour change assume that engagement in a given behaviour is a function of individual threat appraisals, beliefs regarding the performance of behaviour, self-efficacy for performing the desired behaviour and/or dispositions to act (e.g. behavioural intentions). To date, little is known about the impact of cardiovascular imaging interventions on these constructs. This article summarises evidence related to perceived threat, efficacy beliefs, and behavioural intentions after CVD screening. We identified 10 studies (2 RCTs and 8 non-randomised studies, n = 2498) through a combination of screening citations from published systematic reviews and meta-analyses and searching electronic databases. Of these, 7 measured behavioural intentions and perceived susceptibility and 3 measured efficacy beliefs. Findings showed largely encouraging effects of screening interventions on bolstering self-efficacy beliefs and strengthening behavioural intentions. Imaging results that suggest the presence of coronary or carotid artery disease also increased perceived susceptibility to CVD. However, the review also identified some gaps in the literature, such as a lack of guiding theoretical frameworks and assessments of critical determinants of health-related behaviours. By carefully considering the key issues highlighted in this review, we can make significant strides towards reducing CVD risks and improving population health.

This systematic narrative review sought to comprehensively report evidence related to individual responses to cardiovascular screening interventions. Theoretically, the study builds upon theories based on the cognitive perspective (e.g. Health Belief Model, Protection Motivation Theory), which supports the examination of individual perceptions of negative health-related outcomes or health risk, beliefs regarding the performance of a behaviour or outcome expectancies (e.g. perceived benefits of behavioural performance), personal control or capacity to perform a behaviour and/or willingness to invest the effort to engage in behaviour after behavioural intervention delivery. These concepts are considered key predictors of health-related behaviours and have been examined in several public health interventions. Using a variety of search strategies, studies that reported outcomes of interest were identified. Some studies showed that cardiovascular screening interventions may help people form the desired intention to engage in health-related behaviours. We also observed (largely) encouraging effects of cardiovascular screening interventions on individual confidence to engage in health-related behaviours and understanding of personal health risks. However, we identified some limitations in the design, delivery and outcomes assessed in the studies included. For future research, key recommendations to inform the design and delivery of health behaviour interventions are provided.

Update on advanced interventional neuromodulatory approaches to lower blood pressure.

Herein, we review interventional peripheral neuromodulatory approaches to reduce blood pressure (BP), specifically focusing on catheter-based renal denervation (RDN), as well as the latest data from recent clinical trials underpinning its clinical use. Given the apparent failure of established lifestyle measures and pharmacologic BP-lowering approaches to improve hypertension (HTN) control rates, the past decade has seen remarkable scientific efforts to explore the utility of interventional strategies for BP management. Experimental studies and human clinical trials have demonstrated the crucial role of the sympathetic nervous system in the development and mainenance of HTN - consequently, most recent interventional technologies aimed primarily at modulating neural pathways. Advanced approaches that were rigorously tested in human studies include RDN, endovascular baroreflex amplification, baroreflex activation therapy and cardiac neuromodulation stimulation.Amongst these, RDN is by far the most established technology. With recent robust evidence from clinical trials and real-world data showing the safety and efficacy of both ultrasound and radiofrequency-based approaches, a recent clinical consensus statement of the European Society of Cardiology Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions concludes that RDN represents an ancillary therapeutic option in patients with uncontrolled resistant HTN confirmed by ambulatory blood pressure measurement and in spite of attention to lifestyle changes and optimised pharmacological treatment. Furthermore, RDN could alos be considered for patienst unlikley to adhere to or tolerate long-term antihypertensive drug treatment. Very recent data indicate long-term safety and efficacy up to 10 years. Appropriate implementation of RDN into clinical practice is now warranted.For all other interventions additional data from adequately designed human studies are required to establish their safety and clinical utility for potential future use in routine practice.

Efficacy and safety of sodium glucose cotransporter 2 inhibitors plus standard care in diabetic kidney disease: A systematic review and meta-analysis.

INTRODUCTION: Many people with type 2 diabetes progress to end-stage diabetic kidney disease (DKD) despite blockade of the renin-angiotensin system, suggesting the need for innovative treatment options for DKD. To capture the findings of recent studies, we performed an updated systematic review and meta-analysis of the efficacy and safety of sodium glucose co-transporter 2 (SGLT2) inhibitors combined with standard care involving angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) on the development and progression of DKD in people with type 2 diabetes compared with standard care alone. METHODS: The Cochrane Library, MEDLINE, EMBASE, PubMed and clinical trials registers were systematically searched for randomized controlled trials published before 1 September 2022. Primary outcomes were urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Secondary outcomes were glycated hemoglobin (HbA1c) and systolic blood pressure (SBP). Relative risk was calculated for adverse events. RESULTS: Eight studies enrolling 5512 participants were included. In the meta-analysis (n = 1327), SGLT2 inhibitors were associated with a statistically significant reduction in UACR (weighted mean difference [WMD] -105.61 mg/g, 95 % CI -197.25 to -13.98, I2 = 99 %, p = 0.02). There was no statistically significant difference in relation to eGFR (n = 1375; WMD -0.23 mL/min/1.73m2, 95 % CI -4.34 to 3.89, I2 = 94 %, p = 0.91). CONCLUSIONS: SGLT2 inhibitors in addition to standard care including ACE inhibitors and/or ARBs significantly reduced albuminuria, HbA1c and SBP when compared to standard care alone, supporting their routine use in people with type 2 diabetes.

Vitamin K1 Intake and Incident Diabetes in the Danish Diet, Cancer, and Health Study.

CONTEXT: Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors. OBJECTIVE: To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes. METHODS: Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models. RESULTS: In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P < .0001). Compared to participants with the lowest vitamin K1 intake (median:57 µg/d), participants with the highest intakes (median:191 µg/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups. CONCLUSION: Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity).

Computed tomographic angiography in coronary artery disease.

Coronary computed tomographic angiography (CCTA) is becoming the first-line investigation for establishing the presence of coronary artery disease and, with fractional flow reserve (FFRCT), its haemodynamic significance. In patients without significant epicardial obstruction, its role is either to rule out atherosclerosis or to detect subclinical plaque that should be monitored for plaque progression/regression following prevention therapy and provide risk classification. Ischaemic non-obstructive coronary arteries are also expected to be assessed by non-invasive imaging, including CCTA. In patients with significant epicardial obstruction, CCTA can assist in planning revascularisation by determining the disease complexity, vessel size, lesion length and tissue composition of the atherosclerotic plaque, as well as the best fluoroscopic viewing angle; it may also help in selecting adjunctive percutaneous devices (e.g., rotational atherectomy) and in determining the best landing zone for stents or bypass grafts.

The association between breast arterial calcification and atherosclerotic cardiovascular disease in an Australian population-based breast cancer case-control study.

PURPOSE: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality. Breast arterial calcification (BAC) on mammograms is not associated with breast cancer risk. However, there is increasing evidence supporting its association with cardiovascular disease (CVD). This study examines the association between BAC and ASCVD and their risk factors within an Australian population-based breast cancer study. MATERIALS AND METHODS: Data from the controls who participated in the breast cancer environment and employment study (BCEES) were linked with the Western Australian Department of Health Hospital Morbidity database and Mortality Registry to obtain ASCVD outcomes and related risk factor data. Mammograms from participants with no prior history of ASCVD were assessed for BAC by a radiologist. Cox proportional hazards regression was used to examine the association between BAC and later occurrence of an ASCVD event. Logistic regression was used to investigate the factors associated with BAC. RESULTS: A total of 1020 women with a mean age of 60 (sd = 7.0 years) were included and BAC found in 184 (18.0%). Eighty (7.8%) of the 1020 participants developed ASCVD, with an average time to event of 6.2 years (sd = 4.6) from baseline. In univariate analysis, participants with BAC were more likely to have an ASCVD event (HR = 1.96 95% CI 1.29-2.99). However, after adjusting for other risk factors, this association attenuated (HR = 1.37 95% CI 0.88-2.14). Increasing age (OR = 1.15, 95% CI 1.12-1.19) and parity (pLRT < 0.001) were associated with BAC. CONCLUSION: BAC is associated with increased ASCVD risk, but this is not independent of cardiovascular risk factors.

Lipoprotein(a) Is Associated with Thrombus Burden in Culprit Arteries of Younger Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Lipoprotein(a) (Lp[a]) is a risk factor for cardiovascular disease. The burden of thrombus in ST-segment elevation myocardial infarction (STEMI) has implications on treatment and outcomes. However, the association between Lp(a) and atherothrombosis in STEMI remains unclear. OBJECTIVES: The aim of the study was to determine the association between Lp(a) and culprit artery thrombus burden in younger patients with STEMI. METHODS: This was a single-center study of 83 patients aged <65 years with STEMI between 2016-2018 who underwent percutaneous coronary intervention and measurement of Lp(a); those receiving thrombolytic therapy were excluded. Thrombus burden in the culprit artery was determined angiographically using the Thrombolysis In Myocardial Infarction score and classified as absent-to-small, moderate, or large. Elevated Lp(a) was defined as plasma mass concentration >30 mg/dL. Multivariate analysis was performed adjusting for cardiovascular risk factors. RESULTS: The mean age was 48.0 ± 8.4 years, and 78.3% were male. Thirteen (16%), 9 (11%), and 61 (73%) patients had small, moderate, or large thrombus burden, respectively, and 34 (41%) had elevated Lp(a). Elevated Lp(a) was associated with greater thrombus burden compared to normal Lp(a) (large burden 85% vs. 65%; p = 0.024). Elevated Lp(a) was associated with moderate or large thrombus in univariate (OR 10.70 [95% CI 1.32-86.82]; p = 0.026) and multivariate analysis (OR 10.33 [95% CI 1.19-89.52]; p = 0.034). Lp(a) was not associated with culprit artery or stenosis location according to culprit artery. CONCLUSIONS: Elevated Lp(a) is associated with greater thrombus burden in younger patients with STEMI. The finding of this observational study accords with the thrombotic and anti-fibrinolytic properties of Lp(a). A causal relationship requires verification.