Dyslipidemia in American Indian Adolescents and Young Adults: Strong Heart Family Study.

BACKGROUND: Although many studies on the association between dyslipidemia and cardiovascular disease (CVD) exist in older adults, data on the association among adolescents and young adults living with disproportionate burden of cardiometabolic disorders are scarce. METHODS AND RESULTS: The SHFS (Strong Heart Family Study) is a multicenter, family-based, prospective cohort study of CVD in an American Indian populations, including 12 communities in central Arizona, southwestern Oklahoma, and the Dakotas. We evaluated SHFS participants, who were 15 to 39 years old at the baseline examination in 2001 to 2003 (n=1440). Lipids were measured after a 12-hour fast. We used carotid ultrasounds to detect plaque at baseline and follow-up in 2006 to 2009 (median follow-up=5.5 years). We identified incident CVD events through 2020 with a median follow-up of 18.5 years. We used shared frailty proportional hazards models to assess the association between dyslipidemia and subclinical or clinical CVD, while controlling for covariates. Baseline dyslipidemia prevalence was 55.2%, 73.6%, and 78.0% for participants 15 to 19, 20 to 29, and 30 to 39 years old, respectively. Approximately 2.8% had low-density lipoprotein cholesterol ≥160 mg/dL, which is higher than the recommended threshold for lifestyle or medical interventions in young adults of 20 to 39 years old. During follow-up, 9.9% had incident plaque (109/1104 plaque-free participants with baseline and follow-up ultrasounds), 11.0% had plaque progression (128/1165 with both baseline and follow-up ultrasounds), and 9% had incident CVD (127/1416 CVD-free participants at baseline). Plaque incidence and progression were higher in participants with total cholesterol ≥200 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, or non-high-density lipoprotein cholesterol ≥130 mg/dL, while controlling for covariates. CVD risk was independently associated with low-density lipoprotein cholesterol ≥160 mg/dL. CONCLUSIONS: Dyslipidemia is a modifiable risk factor that is associated with both subclinical and clinical CVD, even among the younger American Indian population who have unexpectedly high rates of significant CVD events. Therefore, this population is likely to benefit from a variety of evidence-based interventions including screening, educational, lifestyle, and guideline-directed medical therapy at an early age.

Association of Achievement of the American Heart Association's Life's Essential 8 Goals With Incident Cardiovascular Diseases in the SHFS.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in American Indian people. In 2022, the American Heart Association developed the Life's Essential 8 goals to promote cardiovascular health (CVH) for Americans, composed of diet, physical activity, nicotine exposure, sleep, body mass index, blood lipids, blood pressure, and blood glucose. We examined whether achievement of Life's Essential 8 goals was associated with incident CVD among SHFS (Strong Heart Family Study) participants. METHODS AND RESULTS: A total of 2139 SHFS participants without CVD at baseline were included in analyses. We created a composite CVH score based on achievement of Life's Essential 8 goals, excluding sleep. Scores of 0 to 49 represented low CVH, 50 to 69 represented moderate CVH, and 70 to 100 represented high CVH. Incident CVD was defined as incident myocardial infarction, coronary heart disease, congestive heart failure, or stroke. Cox proportional hazard models were used to examine the relationship of CVH and incident CVD. The incidence rate of CVD at the 20-year follow-up was 7.43 per 1000 person-years. Compared with participants with low CVH, participants with moderate and high CVH had a lower risk of incident CVD; the hazard ratios and 95% CIs for incident CVD for moderate and high CVH were 0.52 (95% CI, 0.40-0.68) and 0.25 (95% CI, 0.14-0.44), respectively, after adjustment for age, sex, education, and study site. CONCLUSIONS: Better CVH was associated with lower CVD risk which highlights the need for comprehensive public health interventions targeting CVH promotion to reduce CVD risk in American Indian communities.

Developing a Charlson Comorbidity Index for the American Indian Population Using the Epidemiologic Data from the Strong Heart Study.

Background: The Charlson Comorbidity Index (CCI) is a frequently used mortality predictor based on a scoring system for the number and type of patient comorbidities health researchers have used since the late 1980s. The initial purpose of the CCI was to classify comorbid conditions, which could alter the risk of patient mortality within a one-year time frame. However, the CCI may not accurately reflect risk among American Indians because they are a small proportion of the U.S. population and possibly lack representation in the original patient cohort. A motivating factor in calibrating a CCI for American Indians is that this population, as a whole, experiences a greater burden of comorbidities, including diabetes mellitus, obesity, cancer, cardiovascular disease, and other chronic health conditions, than the rest of the U.S. population. Methods: This study attempted to modify the CCI to be specific to the American Indian population utilizing the data from the still ongoing The Strong Heart Study (SHS) - a multi-center population-based longitudinal study of cardiovascular disease among American Indians.A one-year survival analysis with mortality as the outcome was performed using the SHS morbidity and mortality surveillance data and assessing the impact of comorbidities in terms of hazard ratios with the training cohort. A Kaplan-Meier plot for a subset of the testing cohort was used to compare groups with selected mCCI-AI scores. Results: A total of 3,038 Phase VI participants from the SHS comprised the study population for whom mortality and morbidity surveillance data were available through December 2019. The weights generated by the SHS participants for myocardial infarction, congestive heart failure, and high blood pressure were greater than Charlson's original weights. In addition, the weights for liver illness were equivalent to Charlson's severe form of the disease. Lung cancer had the greatest overall weight derived from a hazard ratio of 8.308. Conclusions: The mCCI-AI was a statistically significant predictor of one-year mortality, classifying patients into different risk strata X2 (8, N = 1,245) = 30.56 (p = .0002). The mCCI-AI exhibited superior performance over the CCI, able to discriminate between participants who died and those who survived 73% of the time.

Antero-lateral vs. antero-posterior electrode position for cardioversion of atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple randomized controlled trials (RCTs) have compared the success of antero-lateral vs. antero-posterior electrode position for cardioversion of atrial fibrillation (AF). However, due to small sample size and conflicting results of these RCTs, the optimal electrode positioning for successful cardioversion remains uncertain. METHODS: A systematic search of MEDLINE and EMBASE was conducted. Outcomes of interest included overall success of cardioversion with restoration of sinus rhythm, 1st shock success, 2nd shock success, mean shock energy required for successful cardioversion, mean number of shocks required for successful cardioversion, success of cardioversion at high energy (> 150 J) and success of cardioversion at low energy (< 150 J). Mantel-Haenszel risk ratios (RR) with 95% confidence intervals were calculated using random-effects model. RESULTS: A total of 14 RCTs comprising 2445 patients were included. There was no statistically significant difference between two cardioversion approaches in the overall success of cardioversion (RR 1.02; 95% CI [0.97-1.06]; p = 0.43), first shock success (RR 1.14; 95% CI [0.99-1.32]), second shock success (RR 1.08; 95% CI [0.94-1.23]), mean shock energy required (mean difference 6.49; 95% CI [-17.33-30.31], success at high energy > 150 J (RR 1.02; 95% CI [0.92-1.14] and success at low energy < 150 J (RR 1.09; 95% CI [0.97-1.22]). CONCLUSIONS: This meta-analysis of RCTs shows no significant difference in the success of cardioversion between antero-lateral vs. antero-posterior electrode position for cardioversion of AF. Large well-conducted and adequately powered randomized clinical trials are needed to definitively address this question.

Dual therapy with oral anticoagulation and single antiplatelet agent versus monotherapy with oral anticoagulation alone in patients with atrial fibrillation and stable ischemic heart disease: a systematic review and meta-analysis.

BACKGROUND: In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference. We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT). METHODS: A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method. RESULTS: Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36-2.63]). CONCLUSIONS: In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.

A community health promotion project: Amazing Race for Heart Health.

Introduction: American Indians have higher rates of cardiovascular disease (CVD), likely due to disproportionate burden of diabetes and limited access to widespread CVD prevention programs such as Honoring the Gift of Heart Health (HGHH), a 10-week CVD risk factor awareness curriculum. Due to its length, HGHH may be difficult to complete; therefore, we aimed to evaluate a shortened CVD risk factor awareness program based on the HGHH educational materials for American Indians residing in southwest Oklahoma, entitled "The Amazing Race for Heart Health." Methods: We conducted an interventional study where each participant served as their own control (n = 61), with pre- and post-intervention measurements. We included American Indians from seven tribal nations in southwest Oklahoma. At two interventional meetings we used educational materials and activities from HGHH focusing on nutrition, cholesterol, diabetes, hypertension, physical activity, and heart attack warning signs. McNemar's test was used to determine the effectiveness of the intervention on raising CVD risk factor awareness. Results: When comparing the pre- and post-survey responses, the percentage of correct responses either stayed the same or increased. Knowledge improved in 11/25 (44%, p < 0.05) domains including the difference between good and bad cholesterol and types of physical activity that can prevent CVD. When considering diabetes, knowledge increased regarding the interaction between diabetes and cholesterol in the association with CVD. Discussion: These results demonstrate that the "Amazing Race for Heart Health," a shortened CVD risk factor educational program based on the HGHH educational materials, was effective at increasing awareness regarding CVD risk factors.

Subclinical atherosclerosis in adolescents and young adults and the risk of cardiovascular disease: The Strong Heart Family Study (SHFS).

BACKGROUND AND AIMS: Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Although we have observed an association between atherosclerosis and CVD in older adults, the potential association among young AI is unclear. Therefore, we aim to describe the prevalence of atherosclerosis among young AI and determine its association with CVD and all-cause mortality. METHODS AND RESULTS: We evaluated AI participants from the Strong Heart Family Study (SHFS), who were <40 years old and CVD free at the baseline examination, 2001-2003 (n = 1376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified CVD events and all-cause mortality through 2019, with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between atherosclerosis and time to CVD event or all-cause mortality, while controlling for covariates. Among 1376 participants, 71 (5.2%) had atherosclerosis at baseline. During follow-up, 120 (8.7%) had CVD events and 104 (7.6%) died from any cause. CVD incidence was higher in participants who had baseline atherosclerosis (13.51/1000 person-years) than in those who did not (4.95/1000 person-years, p = 0.0003). CVD risk and all-cause mortality were higher in participants with atherosclerosis, while controlling for covariates (CVD HR = 1.85, 95%CI = 1.02-3.37, p = 0.0420; all-cause mortality HR = 2.04, 95%CI = 1.07-3.89, p = 0.0291). CONCLUSIONS: Among young AI, atherosclerosis was independently associated with incident CVD and all-cause mortality later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life.

Safety and feasibility of same-day discharge for catheter ablation of atrial fibrillation: a systematic review and meta-analysis.

PURPOSE: Most centers performing catheter ablation (CA) of atrial fibrillation (AF) admit the patients for an overnight hospital stay to monitor for post-procedure complications, but the clinical benefits of this overnight hospital admission policy have not been carefully investigated. We hypothesized that same-day discharge strategy is safe and feasible in patients with AF undergoing CA. METHODS: A systematic review of studies comparing the safety of same-day discharge vs hospital admission for AF patients undergoing CA was conducted in PubMed/MEDLINE, Embase, Scopus, and Web of Science. No randomized controlled trials met the inclusion criteria; therefore, observational cohort studies were included. Mantel-Haenszel risk ratios were calculated and I2 statistics were reported for heterogeneity assessment. RESULTS: A total of 8 observational studies with 10,102 patients were included. There were no statistically significant differences between same-day discharge vs hospital admission in all studied outcomes including post-discharge 30-day hospital visits (RR: 0.90; 95% CI: 0.40-2.02; p = 0.81), post-discharge vascular/bleeding complications (RR: 0.93; 95% CI: 0.46-1.88; p = 0.85), post-discharge stroke/transient ischemic attack/thromboembolism (RR: 0.70; 95% CI: 0.23-2.20; p = 0.55), and post-discharge recurrent arrhythmias (RR: 0.81; 95% CI: 0.60-1.09; p = 0.1). CONCLUSION: In carefully selected AF patients undergoing CA, same-day discharge strategy is feasible and safe. There are no significant differences in post-discharge 30-day hospital visits, post-discharge vascular complications, and other safety outcomes. Randomized trials are needed to validate these hypothesis-generating findings.

Morbidities and mortality in patients with hereditary thrombotic thrombocytopenic purpura.

Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare disorder caused by severe ADAMTS13 deficiency. Major morbidities and death at a young age are common. Although replacement of ADAMTS13 can prevent morbidities and death, current regimens of plasma prophylaxis are insufficient. We identified 226 patients with hTTP in 96 reports published from 2001 through 2020. Age at diagnosis was reported for 202 patients; 117 were female and 85 were male. The difference was caused by diagnosis of 34 women during pregnancy, suggesting that many men and nulliparous women are not diagnosed. Eighty-three patients had severe jaundice at birth; hTTP was suspected and effectively treated in only 3 infants. Of the 217 patients who survived infancy, 73 (34%) had major morbidities defined as stroke, kidney injury, or cardiac injury that occurred at a median age of 21 years. Sixty-two patients had stroke; 13 strokes occurred in children age 10 years or younger. Of the 54 patients who survived their initial major morbidity and were subsequently observed, 37 (69%) had sustained or subsequent major morbidities. Of the 39 patients who were observed after age 40 years, 20 (51%) had experienced a major morbidity. Compared with an age- and sex-matched US population, probability of survival was lower at all ages beginning at birth. Prophylaxis was initiated in 45 patients with a major morbidity; in 11 (28%), a major morbidity recurred after prophylaxis had begun. Increased recognition of hTTP and more effective prophylaxis started at a younger age are required to improve health outcomes.

Severe thrombocytopenia and microangiopathic hemolytic anemia in pregnancy: A guide for the consulting hematologist.

A hematologist receives a call from a maternal-fetal medicine (MFM) physician about a previously healthy patient who became ill at 25 weeks' gestation. Her mental status is deteriorating. There are signs of fetal distress. Platelet count and hemoglobin are falling. The MFM physician is considering the hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome. For the hematologist, everything seems unfamiliar. Our goal is to provide hematologists with the fundamental knowledge required for understanding and managing these patients who become suddenly and seriously ill during pregnancy and in whom thrombocytopenia and microangiopathic hemolytic anemia are part of their presentation.

Methods for Assessing Willingness to Try and Vegetable Consumption among Children in Indigenous Early Childcare Settings: The FRESH Study.

Food preferences begin in early childhood, and a child's willingness to try (WTT) new vegetables is an important determinant of vegetable intake. Young children living in rural communities are at increased risk for food insecurity, which may limit exposure to and consumption opportunities for vegetables. This manuscript describes the validation of the Farfan-Ramirez WTT (FR-WTT) measure using baseline data from the FRESH study, a gardening intervention for Native American families with preschool-aged children in Osage Nation, Oklahoma. Individually weighed vegetable containers were prepared with six types of vegetables and ranch dip. Researchers presented children (n = 164; M = 4.3 years, SD = 0.8) with these vegetables preceding a snack- or lunch time and recorded the child's FR-WTT for each vegetable using a 5-point scale, ranging from "did not remove food (0)" to "put food in mouth and swallowed (4)". After the presentation period, contents were re-weighed to calculate vegetable consumption. Household parents/guardians completed the Child Food Neophobia Scale (CFNS) for their child. FR-WTT scores were positively correlated with consumption weights of all vegetables (r = 0.7613, p < 0.0001) and each vegetable individually (r = 0.2016-0.7664). The total FR-WTT score was inversely correlated with the CFNS score (r = 0.3268, p < 0.0001). Sensitivity analyses demonstrated similar relationships by BMI, food security, and age. In conclusion, the FR-WTT is a valid method for assessing young children's vegetable eating behavior and intake.

Population assignment reveals low migratory connectivity in a weakly structured songbird.

Understanding migratory connectivity is essential for determining the drivers behind population dynamics and for implementing effective conservation strategies for migratory species. Genetic markers provide a means to describe migratory connectivity; however, they can be uninformative for species with weak population genetic structure, which has limited their application. Here, we demonstrated a genomic approach to describing migratory connectivity in the prothonotary warbler, Protonotaria citrea, a Neotropical songbird of conservation concern. Using 26,189 single nucleotide polymorphisms (SNPs), we revealed regional genetic structure between the Mississippi River Valley and the Atlantic Seaboard with overall weak genetic differentiation among populations (FST  = 0.0055; 95% CI: 0.0051-0.0059). Genetic variation had a stronger association with geographic rather than environmental factors, with each explaining 14.5% and 8.2% of genetic variation, respectively. By varying the numbers of genomic markers used in population assignment models with individuals of known provenance, we identified a maximum assignment accuracy (89.7% to site, 94.3% to region) using a subset of 600 highly differentiated SNPs. We then assigned samples from nonbreeding sites to breeding region and found low migratory connectivity. Our results highlight the importance of filtering markers for informative loci in models of population assignment. Quantifying migratory connectivity for weakly structured species will be useful for expanding studies to a wider range of migratory species across taxonomic groups and may contribute to a deeper understanding of the evolution of migratory strategies.

Platelet Counts during Pregnancy.

BACKGROUND: Platelet counts of less than 150,000 per cubic millimeter during uncomplicated pregnancies are described as gestational thrombocytopenia if no alternative cause is identified. Platelet counts may be even lower in women with pregnancy-related complications. However, the occurrence and severity of thrombocytopenia throughout pregnancy are not defined. METHODS: We evaluated platelet counts throughout pregnancy in women who delivered at Oklahoma University Medical Center between 2011 and 2014. These platelet counts were compared with those of nonpregnant women who were included in the National Health and Nutrition Examination Survey from 1999 through 2012. RESULTS: Among the 15,723 deliveries that occurred during the study period, 7351 women had sufficient data for our analyses. Of these women, 4568 had uncomplicated pregnancies, 2586 had pregnancy-related complications, and 197 had preexisting disorders associated with thrombocytopenia. Among the women who had uncomplicated pregnancies, the mean platelet count in the first trimester (mean gestation, 8.7 weeks) was 251,000 per cubic millimeter, which was lower than the mean platelet count in the 8885 nonpregnant women (273,000 per cubic millimeter) (P<0.001). At the time of delivery, 9.9% of the women with uncomplicated pregnancies had a platelet count below 150,000 per cubic millimeter. During the course of the uncomplicated pregnancies and deliveries, only 45 women (1.0%) had a platelet count below 100,000 per cubic millimeter. Among the 12 women with uncomplicated pregnancies who had a platelet count below 80,000 per cubic millimeter, only 5 (0.1%, among whom the range of platelet counts was 62,000 to 78,000 per cubic millimeter; median, 65,000) were identified by medical record review as having no alternative cause for the thrombocytopenia. Platelet counts of less than 150,000 per cubic millimeter at the time of delivery were more common among women who had pregnancy-related complications than among women who had uncomplicated pregnancies (11.9% vs. 9.9%, P=0.01). Throughout their pregnancies and deliveries, 59 women (2.3%) with pregnancy-related complications had a platelet count below 100,000 per cubic millimeter, and 31 (1.2%) had a platelet count below 80,000 per cubic millimeter. CONCLUSIONS: Mean platelet counts decreased during pregnancy in all the women, beginning in the first trimester. In women who have a platelet count of less than 100,000 per cubic millimeter, a cause other than pregnancy or its complications should be considered. (Funded by the National Heart, Lung, and Blood Institute.).

Platelet counts in women with normal pregnancies: A systematic review.

The occurrence of thrombocytopenia in 5% of pregnant women at delivery, described as gestational thrombocytopenia, is well documented. A commonly believed concept is that gestational thrombocytopenia is the result of gradually decreasing platelet counts in all women during pregnancy. The goal of our study was to evaluate the data supporting this concept. To learn what is known about platelet counts throughout normal pregnancies, we systematically reviewed all publications describing platelet counts during pregnancy. We identified 3,039 studies; 46 reporting ≥30 women with normal pregnancies were included in our analyses. The combined mean platelet counts from all studies supported the concept that platelet counts decrease during pregnancy and increase postpartum: first trimester, 251,000/µL (95% CI, 238,000-264,000/µL); second trimester, 238,000/µL (95% CI, 222,000-253,000/µL); third trimester, 224,000/µL (95% CI, 213,000-235,000/µL); delivery, 237,000/µL (95% CI, 209,000-264,000/µL); 4-8 weeks postpartum, 247,000/µL (95% CI, 207,000-287,000/µL). However, individual studies were inconsistent. Eleven longitudinal studies compared platelet counts on the same women at different times during gestation: seven reported a decrease; four reported no change. Ten cross-sectional studies compared platelet counts of different women at different times during gestation: five reported a decrease; five reported no change. Five studies compared platelet counts of pregnant to nonpregnant women: three reported that platelet counts were lower in pregnant women; one reported no difference; one reported that platelet counts were higher in pregnant women. These inconsistent data emphasize the need to accurately describe platelet counts throughout normal pregnancies. Accurate data are essential for evaluating the clinical importance of thrombocytopenia during pregnancy.