Hypertension and Brachydactyly Syndrome: Genetic Insights and a Novel Presentation.

Phosphodiesterase 3A (PDE3A) gene mutations have recently been associated with hypertension and brachydactyly syndrome (HTNB). This report shows how the recent recognition of the role of the PDE3A gene in HTNB facilitated the diagnosis of HTNB in a 20-year-old female who could not be diagnosed at her initial presentation at 6 years of age.

Carpal Tunnel Syndrome and Transthyretin Amyloidosis in the All of Us Research Program.

OBJECTIVE: To evaluate the association of carpal tunnel syndrome (CTS) with incident heart failure and incident amyloidosis and to assess the risk of CTS in pathogenic TTR genetic variant carriers. METHODS: This prospective cohort study included multiethnic US adults 18 years of age and older without prevalent heart failure and amyloidosis with available genotypic data from the All of Us Research Program. The primary outcomes were incident heart failure and incident amyloidosis. The association of incident heart failure and incident amyloidosis with CTS was assessed using multivariable adjusted Cox models accounting for age, sex, race and ethnicity, obesity, hypertension, diabetes, statin use, and smoking status. RESULTS: Of the 166,987 individuals included, the median age was 54 (38 to 66) years; 105,279 (63.0%) were female, and 92,780 (55.6%) were non-Hispanic White individuals; CTS was identified in 12,407 (7.4%) individuals. Compared with individuals without CTS, the adjusted hazard ratio for incident heart failure was 1.13 (95% CI, 1.02 to 1.26) in individuals with CTS. The risk of amyloidosis was ∼3-fold higher (adjusted hazard ratio, 2.86; 95% CI, 1.71 to 4.77) in individuals with CTS compared with those without CTS. Individuals carrying a pathogenic TTR variant had an approximately 40% higher risk (adjusted hazard ratio, 1.38; 95% CI, 1.16 to 1.65) for development of CTS compared with noncarriers. CONCLUSION: Cardiac amyloidosis screening programs may use CTS as a sentinel event and use genetic testing to identify individuals at a higher risk of TTR amyloidosis.

Trends of Lipid Concentrations, Awareness, Evaluation, and Treatment in Severe Dyslipidemia in US Adults.

OBJECTIVE: To evaluate the contemporary trends of lipid concentrations, cholesterol evaluation, hypercholesterolemia awareness, and statin use among individuals with severe dyslipidemia (low-density lipoprotein cholesterol [LDL-C] level ≥190 mg/dL) between 2011 and 2020. PATIENTS AND METHODS: This serial cross-sectional analysis included nonpregnant adults ≥20 years of age from the National Health and Nutrition Examination Survey between 2011 and 2020. Age-adjusted weighted trends of LDL-C, triglycerides, cholesterol evaluation in the past 5 years, hypercholesterolemia awareness, and documented statin use among individuals with severe dyslipidemia were estimated. RESULTS: Among 24,722 participants included, the prevalence of severe dyslipidemia was 5.4% (SE: 0.2%) which was stable across the study period (Ptrend=.78). Among individuals with severe dyslipidemia (mean age: 55.3 [SE: 0.7] years; 52.2% females; 68.8% non-Hispanic White), LDL-C (224.3 [SE: 4.2] mg/dL in 2011-2012 to 224.2 [SE: 4.6] mg/dL in 2017-2020; Ptrend =.83), and triglyceride (123.3 [SE: 1.1] mg/dL in 2011-2012 to 101.8 [SE: 1.1] mg/dL in 2017-2020; Ptrend=.13), levels remained stable from 2011 to 2020. The rates of cholesterol evaluation in the past 5 years (72.0% [SE: 5.7%] in 2011-2012 to 78.0% [SE: 4.8%] in 2017-2020; Ptrend=.91), hypercholesterolemia awareness (48.1% [SE: 5.5%] in 2011-2012 to 51.9% [SE: 5.8%] in 2017- 2020; Ptrend=.77), and documented statin use (34.7% [SE: 4.5%] in 2011-2012 to 33.4% [SE: 4.0%] in 2017-2020; Ptrend=.28) remained stagnant in individuals with severe dyslipidemia between 2011 and 2020. CONCLUSION: Among individuals with severe dyslipidemia, cholesterol evaluation and hypercholesterolemia awareness rates were stable at ∼75% and ∼50% in the past decade. Only ∼34% of individuals with severe dyslipidemia took statins between 2011 and 2020, which likely contributed to the stable LDL-C levels noted across the study period. Further investigations into the determinants of statin use and adherence to statins are needed.

Natriuretic Peptide Normative Levels and Deficiency: The National Health and Nutrition Examination Survey.

BACKGROUND: Natriuretic peptides (NPs) are hormones with a range of key functions vital for cardiometabolic health. However, the reference ranges of NPs and the prevalence of NP deficiency in the healthy United States population remains poorly defined. OBJECTIVES: This study aims to establish the reference range for N-terminal pro-B-type natriuretic peptide (NT-proBNP) values and to assess the prevalence of NP deficiency in a nationally representative healthy United States population. METHODS: Healthy participants with NT-proBNP measurements from the 1999-2004 National Health and Nutrition Examination Survey were included. Weighted multivariable-adjusted linear regression models were used to assess the adjusted percentage difference of NT-proBNP concentrations by sex and race and ethnicity. NP deficiency was defined as concentrations <2.5th percentile in the study cohort. RESULTS: Among 18,145 individuals (median age: 33.9 years [IQR: 17.1-49.0 years], 49.8% males, and 68.5% non-Hispanic White individuals), females had similar NT-proBNP concentrations in the 1-10 years group (4.2% [95% CI: -3.3% to 12.2%]), and highest differences in the 20-30 years group (150.5% [95% CI: 123.5%-180.8%]) compared with males in their respective age groups. Compared with non-Hispanic White individuals, non-Hispanic Black individuals had lower NT-proBNP concentrations in the 1- to 10-years group (19.6% [95% CI: 10.7%-27.6%]), and these differences were most pronounced in the 30-40 years group (40.2% [95% CI: 33.7%-46.0%]). An estimated 9.1 million United States individuals had NP deficiency. NP deficiency was associated with a higher risk of cardiometabolic diseases such as hypertension, dyslipidemia, obesity, and insulin resistance. CONCLUSIONS: This study establishes the normative NP concentrations across the lifespan of a healthy United States population.

Incident Heart Failure Risk Reclassification With Race-Independent Estimated Glomerular Filtration Rate: A National Heart, Lung, and Blood Institute Pooled Cohorts Analysis.

BACKGROUND: This study compared the predictive value of the race-independent creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) and the race-dependent creatinine-based eGFR (eGFRcr) for incident heart failure (HF). METHODS: This study combined the participant-level data from ARIC (Atherosclerosis Risk in Communities) (visit 4) and MESA (Multi-Ethnic Study of Atherosclerosis) (visit 1) to calculate eGFRcr-cys and eGFRcr. The primary outcome of the study was adjudicated incident HF over a follow-up period of 10 years. Multivariable Cox models were used to assess the risk of incident HF with the quartiles of eGFRcr-cys and eGFRcr. RESULTS: Among 15,615 individuals (median age: 62 [57-68] years; 55.0% females; 23.9% Black), the median eGFRcr-cys and eGFRcr were 91.4 (79.4, 102.0) mL/min/1.73m2 and 84.7 (72.0, 94.7) mL/min/1.73m2, respectively. Compared with the fourth quartile of eGFRcr-cys, the hazard ratio for incident HF was 1.02 (95% CI:0.80-1.30) in the third quartile, 1.02 (95% CI:0.80-1.30) in the second quartile, and 1.47 (95% CI:1.16-1.86) in the first quartile. Compared with the 4th quartile of the eGFRcr, the risk of incident HF was similar in the 3rd (HRadj:0.90 [95% CI:0.73-1.12]), 2nd (HRadj: 0.96 [95% CI:0.77-1.20]), and 1st (HRadj:1.15 [95% CI:0.93-1.44]) quartiles. C-statistics were similar for the multivariable-adjusted Cox models for incident HF using eGFRcr (0.80 [0.79-0.81]) and eGFRcr-cys (0.80 [0.79-0.82]). CONCLUSION: The eGFRcr and eGFRcr-cys had comparable predictive values for incident HF.

Self-excited converging shock structure in a complex plasma medium.

We report the study of a self-excited converging shock structure observed in a complex plasma medium. A high-density dust cloud of melamine formaldehyde particles is created and horizontally confined by a circular ring in a dc glow discharge plasma at a particular discharge voltage and pressure. Later, as the discharge voltage is increased, a circular density crest is spontaneously generated around the outer boundary of the dust cloud. This nonlinear density structure is seen to propagate inward towards the center of the dust cloud. The properties of the excited structure are analyzed and found to follow the characteristics of a converging shock structure. A three-dimensional molecular dynamics simulation has also been performed in which a stable dust cloud is formed and levitated by the balance of forces due to gravity and an external electric field mimicking the cathode sheath electric field in the experiment. Particles are also horizontally confined by an external electric field, representing the sheath electric field of the circular ring present in the experiment. A circular shock structure has been excited by applying an external perturbation in the horizontal electric field around the outer boundary of the dust cloud. The characteristic properties of the shock are analyzed in the simulation and qualitatively compared with the experimental findings. This paper is not only of fundamental interest but has many implications concerning the study of converging shock waves excited in other media for various potential applications.

Update on Immunotherapy Cardiotoxicity: Checkpoint Inhibitors, CAR T, and Beyond.

OPINION STATEMENT: Immunotherapy is an innovative approach to cancer treatment that involves using the body's immune system to fight cancer. The landscape of immunotherapy is constantly evolving, as new therapies are developed and refined. Some of the most promising approaches in immunotherapy include immune checkpoint inhibitors (ICIs): these drugs target proteins on the surface of T-cells that inhibit their ability to attack cancer cells. By blocking these proteins, checkpoint inhibitors allow T-cells to recognize and destroy cancer cells more effectively. CAR T-cell therapy: this therapy involves genetically modifying a patient's own T-cells to recognize and attack cancer cells. CAR T-cell therapy exhibits favorable response in many patients with refractory hematological cancers with growing clinical trials in solid tumors. Immune system modulators: these drugs enhance the immune system's ability to fight cancer by stimulating the production of immune cells or inhibiting the activity of immune-suppressing cells. While immunotherapy has shown great promise in the treatment of cancer, it can also pose significant cardiac side effects. Some immunotherapy drugs like ICIs can cause myocarditis, which can lead to chest pain, shortness of breath, and heart failure. Other cardiac side effects of ICIs include arrhythmias, pericarditis, vasculitis, and accelerated atherosclerosis. It is important for patients receiving immunotherapy to be monitored closely for these side effects, as prompt treatment can help prevent serious complications. Patients should also report any symptoms to their healthcare providers right away, so that appropriate action can be taken. CAR T-cell therapy can also illicit an exaggerated immune response creating cytokine release syndrome (CRS) that may precipitate cardiovascular events: arrhythmias, myocardial infarction, and heart failure. Overall, while immune modulating therapy is a promising and expanding approach to cancer treatment, it is important to weigh the potential benefits against the risks and side effects, especially in patients with high risk for cardiovascular complications.

Trends of cardiovascular health in Asian American individuals: A national health and nutrition examination survey study.

Objective: Oversampling of Asian American individuals in the National Health and Nutrition Examination Survey (NHANES) provides a unique opportunity to assess the population-level cardiovascular health (CVH) in the fastest-growing racial group in the US. Methods: The Life's Essential 8 (LE8) score and its components were calculated in self-reported Asian American individuals ≥20 years of age and free of cardiovascular disease in the NHANES cycles from 2011-March 2020. Multivariable adjusted linear and logistic regression models were used for analysis. Results: Among 2,059 Asian American individuals, the weighted mean LE8 score was 69.1 (0.4) with US-born [69.0 (0.8)] and foreign-born individuals [69.1 (0.4)] having similar CVH. From 2011 to March 2020, CVH in the overall population [69.7 (0.8) to 68.1 (0.8); Ptrend: 0.009] and foreign-born individuals [69.7 (0.8) to 67.7 (0.8); Ptrend: 0.005] declined. Decreasing trends were noted in the body mass index score irrespective of stratification and in the blood pressure scores in the overall population and foreign-born Asian American individuals. Compared with US-born individuals, the odds of ideal levels of smoking [ORadj:<5 years: 2.23 (95%CI: 1.45-3.44); 5-15 years: 1.97 (95%CI: 1.27-3.05); 15-30 years: 1.61 (95%CI: 1.11-2.34); ≥30 years: 1.69(95%CI:1.20-2.36)] and diet [ORadj: <5 years: 1.87 (95%CI: 1.26-2.79); 5-15 years: 2.00 (95%CI: 1.38-2.89); 15-30 years: 1.74 (95%CI: 1.14-2.68)] were higher in foreign-born individuals. Foreign-born individuals had lower odds of ideal physical activity levels [ORadj: 5-15 years: 0.55 (95%CI: 0.39-0.79); 15-30 years: 0.68 (95%CI: 0.49-0.95)] and ideal cholesterol levels [ORadj: 5-15 years: 0.59 (95%CI: 0.42-0.82); 15-30 years: 0.54 (95%CI :0.38-0.76); ≥30 years: 0.52 (95%CI: 0.38-0.76)]. Conclusion: The CVH in Asian American individuals declined from 2011 to March 2020. The odds of ideal CVH decreased with increasing duration of stay in the US, with foreign-born individuals residing in the US for ≥30 years having ∼28% lower odds of ideal CVH compared with US-born individuals.

Effect of oral environment on contemporary orthodontic materials and its clinical implications.

Contemporary orthodontics entails using advanced materials and devices, simplifying the process of tooth movement. It is well documented that orthodontic materials are subjected to various fluctuations and stresses in the oral environment, such as salivary pH, dietary habits, temperature changes, and masticatory loads. These changes reduce bonding materials' longevity, plasticize resin polymers, and reduce elastic properties. In addition, the corrosion of orthodontic appliances in the oral environment has concerned clinicians for some time. This is focused on two principal issues: whether corrosion products are absorbed into the body and cause either localized or systemic effects, and the results of corrosion on the physical properties and the clinical performance of orthodontic appliances. Recently, another major concern is the potential release of bisphenol-A from materials containing polymers such as thermoplastic aligners and resins, which is known to induce xenoestrogenicity and cytotoxicity when the tissue level exceeds the daily recommended intake. However, most of these findings are based on in vitro studies that suffer from serious drawbacks such as failure to replicate the exact oral environment and process during orthodontic treatment. Therefore, developing clinically relevant methods should be the goal of future research related to the aging of orthodontic materials. The purpose of this review is to outline the impact of the oral environment on contemporary orthodontic materials.

Sex-Associated Differences in the Clinical Outcomes of Left Ventricular Assist Device Recipients: Insights From Interagency Registry for Mechanically Assisted Circulatory Support.

BACKGROUND: Sex-associated differences in clinical outcomes among left ventricular assist device recipients in the United States have been recognized. However, an investigation of the social and clinical determinants of sex-associated differences is lacking. METHODS: Left ventricular assist device receiving patients enrolled in Interagency Registry for Mechanically Assisted Circulatory Support between 2005 and 2017 were included. The primary outcome was all-cause mortality. Secondary outcomes included heart transplantation and postimplantation adverse event rates. The cohort was stratified by the social subgroup of race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic), and clinical subgroups of device strategy (destination therapy, bridge to transplant, and bridge to candidacy), and implantation center volume (low [≤20 implants/y], medium [21-30 implants/y], and high [>30 implants/y]). A multivariable-adjusted Cox proportional hazard model was used to assess the risk of death and heart transplantation with prespecified interaction testing. Poisson regression was used to estimate adverse events by sex across the various subgroups. RESULTS: Among 18 525 patients, there were 3968 (21.4%) females. Compared with their male counterparts, Hispanic (adjusted hazard ratio [HRadj], 1.75 [1.23-2.47]) females had the highest risk of death followed by non-Hispanic White females (HRadj, 1.15 [1.07-1.25]; Pinteraction=0.02). Hispanic (HRadj, 0.60 [0.40-0.89]) females had the lowest cumulative incidence of heart transplantation followed by non-Hispanic Black females (HRadj, 0.76 [0.67-0.86]), and non-Hispanic White females (HRadj, 0.88 [0.80-0.96]) compared with their male counterparts (Pinteraction<0.001). Compared with their male counterparts, females on the bridge to candidacy strategy (HRadj, 1.32 [1.18-1.48]) had the highest risk of death (Pinteraction=0.01). The risk of death (Pinteraction=0.44) and cumulative incidence of heart transplantation (Pinteraction=0.40) did not vary by sex in the center volume subgroup. A higher incidence rate of adverse events after left ventricular assist device implantation was also seen in females compared with the males, overall, and across all subgroups. CONCLUSIONS: Among left ventricular assist device recipients, the risk of death, the cumulative incidence of heart transplantation, and adverse events differ by sex across the social and clinical subgroups.

Testing dental quality measures: Emergency department visits for nontraumatic dental conditions and subsequent follow-up dental visits.

BACKGROUND: The goal of this study was to test the feasibility, reliability, and validity of the Dental Quality Alliance's adult dental quality measures for system-level implementation for ambulatory care sensitive (ACS) emergency department (ED) visits for nontraumatic dental conditions (NTDCs) in adults and follow-up after ED visits for NTDCs in adults. METHODS: Medicaid enrollment and claims data from Oregon and Iowa were used for measure testing. Testing included validation of diagnosis codes in claims data through patient record reviews of ED visits and calculations of κ statistic, sensitivity, and specificity. RESULTS: Adult Medicaid enrollees' ACS NTDC ED visits ranged from 209 through 310 per 100,000 member-months. In both states, patients in the age category 25 through 34 years and non-Hispanic Black patients had the highest rates of ACS ED visits for NTDCs. Only one-third of all ED visits were associated with a follow-up dental visit within 30 days, decreasing to approximately one-fifth with a 7-day follow-up. The agreement between the claims data and patient records for identification of ACS ED visits for NTDCs was 93%, κ statistic was 0.85, sensitivity was 92%, and specificity was 94%. CONCLUSIONS: Testing revealed the feasibility, reliability, and validity of 2 DQA quality measures. Most beneficiaries did not have a follow-up with a dentist within 30 days of an ED visit. PRACTICAL IMPLICATIONS: Adoption of quality measures by state Medicaid programs and other integrated care systems will enable active tracking of beneficiaries with ED visits for NTDCs and develop strategies to connect them to dental homes.

AHA Life's essential 8 and ideal cardiovascular health among young adults.

Objective: This study assessed cardiovascular health (CVH) in young adults using the 2022 AHA Life's Essential 8 (LE8) score and compared it with the Life's Simple 7 (LS7) score. Methods: Individuals aged 18 to 44 years without a history of cardiovascular disease in the National Health and Nutrition Examination Survey (NHANES) cycles were included. Data from 2007-2008 to 2017-2018 were combined to create 3 groups (2007-2010, 2011-2014, and 2015-2018) for analysis. The LE8 score and its components were computed in the overall population and stratified by sex and race/ethnicity. Trends for the LE8 score were analyzed using adjusted linear regression models. Results: Among 12,197 young adults, representing an estimated 89.4 million individuals, from the NHANES 2007-2018, the CVH in the overall population and across all subgroups was stable (Ptrend >0.05). The blood lipid score improved across all subgroups (Ptrend:<0.05). The mean LE8 score was 69.2±0.3. Females (71.4±0.4) had better CVH compared with males (67.2±0.4). Non-Hispanic Black individuals (65.1± 0.3) had the lowest CVH compared with Non-Hispanic White individuals (69.9±0.5), Mexican American individuals (67.3±0.3), and other race individuals (71.2±0.4). Of the 46.1 million individuals categorized as intermediate CVH by the LS7 score, 8.1 million (17.6%) and 2.3 million (5.0%) were reclassified to poor and ideal CVH by the LE8 score, respectively. Of the 40.1 million individuals categorized as ideal CVH by the LS7 score, 18.9 million (47.1%) and 0.1 million (0.2%) were reclassified to poor CVH and intermediate CVH by the LE8 score, respectively. Conclusion: Among US young adults, there has been no improvement in CVH over the last decade with notable sex and race/ethnicity-associated differences in the LE8 score. Nearly 1 in 4 young adults had ideal CVH using the LE8 score compared with 1 in 2 individuals using the LS7 score.