Family-based cascade screening from index probands is considered an effective way of identifying undiagnosed individuals with familial hypercholesterolemia (FH). The role of genetic testing of the ...proband in the success of cascade screening for FH is unknown.
We randomized 240 individuals with a clinical diagnosis of FH to genetic testing for FH (n = 160) or usual care with lipid testing alone (n = 80). The primary study endpoint was the proportion of probands with at least one relative enrolled in the study within one year after the notification of results.
Proband median age was 59 (47-67) and 71% were female. Only 28 (12%) probands succeeded in enrolling a relative. While the genetic testing group had a higher proportion of probands with relatives enrolled (13.1%) compared with the usual care group (8.8%), this difference was not significant (p = 0.40). In subgroup analyses, enrollment of a relative was higher in the pathogenic variant group (22.7%) compared to the no pathogenic variant (9.5%) and usual care groups (8.8%) (p = 0.04).
We observed a low rate of family participation in cascade screening despite repeated recommendations to probands. Compared to usual care, genetic testing did not improve family participation in cascade screening for FH.
NCT04526457.
The U.S. Centers for Disease Control and Prevention (CDC) recognizes that older adults and individuals with certain medical conditions are at increased risk of severe COVID-19 infection. ...Understanding the proportion of the population at risk of severe infection, including among those with heart disease, could assist current vaccine strategy efforts.
Using data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES), we estimated the weighted prevalence of any of eight of eleven increased-risk conditions (including age ≥65) in U.S. adults aged ≥18 (N = 10,581) and extrapolated these results to a population of 233.8 million U.S. adults ≥18, and subgroups from the overall population defined by race/ethnicity, education, income and history of heart disease.
An estimated 176.1 million individuals representing 75.4% of U.S. adults had at least one increased-risk condition, 40.3% ≥2 and, 18.5% ≥3 conditions. Approximately 129 million adults aged <65 (69.2%) were also estimated to be at increased-risk. Compared to Whites, similar proportions of Blacks in the overall population (78.0 vs. 75.6%, p>0.05) and Hispanics in the younger population (70.8 vs 68.4%) were estimated to be at increased-risk. Conversely, a greater proportion of individuals with lower education and income levels were estimated to be at increased-risk both in the overall and younger population. In addition, an estimated 6.2 million individuals (14.5%) had heart disease. Among these, virtually all had at least one additional CDC risk factor (97.9%) and most had ≥2 or ≥3 risk factors (83.8% and 58.5%, respectively).
As vaccination strategies are being explored, these results demonstrate that >75% of adults in the U.S. would be considered at increased-risk for severe COVID-19 infection by CDC criteria. Risk factor prevalence alone may not adequately capture the totality of risk, particularly among Black and Hispanic racial/ethnic groups and those with heart disease.
The win ratio was introduced into cardiovascular trials as a potentially better way of analyzing composite endpoints to account for the hierarchy of clinical significance of their components and to ...facilitate the inclusion of recurrent events. The basic concept of the win ratio is to define a hierarchy of clinical importance within the components of the composite outcome, form all possible pairs by comparing every subject in the treatment group with every subject in the control group, and then evaluate each pair for the occurrence of the components of the composite outcome in descending order of importance, starting at the most important and progressing down the hierarchy if the outcome does not result in a win in either pair until pairs are tied for the outcome after exhaustion of all components. Although the win ratio offers a novel method of depiction of outcomes in clinical trials, its advantages may be counterbalanced by several fallacies (such as ignoring ties and weighting each hierarchal component equally) and challenges in appropriate clinical interpretation (establishing clinical meaningfulness of the observed effect size). From this perspective, we discuss these and other fallacies and provide a suggested framework to overcome such limitations to enhance utility of this statistical method across the clinical trial enterprise.
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Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit ...from aspirin therapy is unclear.
To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds.
Prospective population-based cohort study of Dallas Heart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020.
Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher.
Major bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis-derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds.
A total of 2191 participants (mean SD, age 44 9.1 years, 1247 women 57%, and 1039 black individuals 47%) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and ≥100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio HR, 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P < .001; HR, 5.3; 95% CI, 3.6-7.9; P < .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk.
Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.
Despite major differences in their health care systems, medical crowdfunding is increasingly used to finance personal health care costs in Canada, the UK, and the US. However, little is known about ...the campaigns designed to raise monetary donations for medical expenses, the individuals who turn to crowdfunding, and their fundraising intent.
To examine the demographic characteristics of medical crowdfunding beneficiaries, campaign characteristics, and their association with funding success in Canada, the UK, and the US.
This cross-sectional study extracted and manually reviewed data from GoFundMe campaigns discoverable between February 2018 and March 2019. All available campaigns on each country domain's GoFundMe medical discovery webpage that benefitted a unique patient(s) were included from Canada, the UK, and the US. Data analysis was performed from March to December 2019.
Campaign and beneficiary characteristics.
Log-transformed amount raised in US dollars.
This study examined 3396 campaigns including 1091 in Canada, 1082 in the UK, and 1223 in the US. Campaigns in the US (median IQR, $38 204 $31 200 to $52 123) raised more funds than campaigns in Canada ($12 662 $9377 to $19 251) and the UK ($6285 $4028 to $12 348). In the overall cohort per campaign, Black individuals raised 11.5% less (95% CI, -19.0% to -3.2%; P = .006) than non-Black individuals, and male individuals raised 5.9% more (95% CI, 2.2% to 9.7%; P = .002) than female individuals. Female (39.4% of campaigns vs 50.8% of US population; difference, 11.3%; 95% CI, 8.6% to 14.1%; P < .001) and Black (5.3% of campaigns vs 13.4% of US population; difference, 8.1%; 95% CI, 6.8% to 9.3%; P < .001) beneficiaries were underrepresented among US campaigns. Campaigns primarily for routine treatment expenses were approximately 3 times more common in the US (77.9% 272 of 349 campaigns) than in Canada (21.9% 55 of 251 campaigns; difference, 56.0%; 95% CI, 49.3-62.7%; P < .001) or the UK (26.6% 127 of 478 campaigns; difference, 51.4%; 95% CI, 45.5%-57.3%; P < .001). However, campaigns for routine care were less successful overall. Approved, inaccessible care and experimental care raised 35.7% (95% CI, 25.6% to 46.7%; P < .001) and 20.9% (95% CI, 13.3% to 29.1%; P < .001), respectively, more per campaign than routine care. Campaigns primarily for alternative treatment expenses (16.1% 174 of 1079 campaigns) were nearly 4-fold more common for cancer (23.5% 144 of 614 campaigns) vs noncancer (6.5% 30 of 465 campaigns) diagnoses.
Important differences were observed in the reasons individuals turn to medical crowdfunding in the 3 countries examined that suggest racial and gender disparities in fundraising success. More work is needed to understand the underpinnings of these findings and their implications on health care provision in the countries examined.
Hypertension remains the major cardiovascular disease risk factor globally, but variability in measured blood pressure may result in suboptimal management. Whether genetic contributors to elevated ...blood pressure may complementarily inform cardiovascular disease risk assessment is unknown.
To examine incident cardiovascular disease by blood pressure polygenic risk score independent of measured blood pressures and antihypertensive medication prescriptions.
The cohort study (UK Biobank) recruited UK residents aged 40 to 69 years between March 2006 and August 2010. Participants without a prior physician diagnosis of cardiovascular disease, including myocardial infarction, stroke, or heart failure, were included. Excluded were individuals with mismatch between self-reported and genotypically inferred sex, sex aneuploidy, missing genotype rates of 1% or greater, and excess genotypic heterozygosity. Data analyses were performed from September 25, 2021, to July 21, 2022.
Measured blood pressure and externally derived blood pressure polygenic risk score stratified by hypertension diagnosis and management, which included normal blood pressure (<130/80 mm Hg without antihypertensives), untreated hypertension (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg without antihypertensives), and treated hypertension (current antihypertensives prescriptions).
Composite of first incident myocardial infarction, stroke, heart failure, or cardiovascular-related death.
Of the 331 078 study participants included (mean SD age at enrollment, 56.9 8.1 years; 178 824 female 54.0%), 83 094 (25.1%) had normal blood pressure, 197 597 (59.7%) had untreated hypertension, and 50 387 (15.2%) had treated hypertension. Over a median (IQR) follow-up of 11.1 (10.4-11.8) years, the primary outcome occurred in 15 293 participants. Among those with normal blood pressure, untreated hypertension, and treated hypertension, each SD increase in measured systolic blood pressure was associated with hazard ratios of 1.08 (95% CI, 0.93-1.25), 1.20 (95% CI, 1.16-1.23), and 1.16 (95% CI, 1.11-1.20), respectively, for the primary outcome. Among these same categories, each SD increase in genetically predicted systolic blood pressure was associated with increased hazard ratios of 1.13 (95% CI, 1.05-1.20), 1.04 (95% CI, 1.01-1.07), and 1.06 (95% CI, 1.02-1.10), respectively, for the primary outcome independent of measured blood pressures and other covariates. Findings were similar for measured and genetically predicted diastolic blood pressure.
Blood pressure polygenic risk score may augment identification of individuals at heightened cardiovascular risk, including those with both normal blood pressure and hypertension. Whether it may also guide antihypertensive initiation or intensification requires further study.
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