Genetic markers of cardiac autonomic neuropathy in the Kazakh population.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. MATERIALS AND METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively). CONCLUSION: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR): design and methodology.

BACKGROUND: Cardiac disease in pregnancy is a major contributor to maternal mortality in high, middle and low-income countries. Availability of data on outcomes of pregnancy in women with heart disease is important for planning resources to reduce maternal mortality. Prospective data on outcomes and risk predictors of mortality in pregnant women with heart disease (PWWHD) from low- and middle-income countries are scarce. METHODS: The Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR) is a prospective, multicentric and multidisciplinary registry of PWWHD from 29 participating sites including both public and private sectors, across the state of Tamil Nadu in India. The TNPHDR is aimed to provide data on incidence of maternal and fetal outcomes, adverse outcome predictors, applicability of the modified World Health Organization (mWHO) classification of maternal cardiovascular risk and the International risk scoring systems (ZAHARA and CARPREG I & II) in Indian population and identify possible gaps in the existing management of PWWHD. Pregnancy and heart teams will be formed in all participating sites. Baseline demographic, clinical, laboratory and imaging parameters, data on counselling received, antenatal triage and management, peripartum management and postpartum care will be collected from 2500 eligible participants as part of the TNPHDR. Participants will be followed up at one, three and six-months after delivery/termination of pregnancy to document study outcomes. Predictors of maternal and foetal outcome will be identified. DISCUSSION: The TNPHDR will be the first representative registry from low- and middle-income countries aimed at providing crucial information on pregnancy outcomes and risk predictors in PWWHD. The results of TNPHDR could help to formulate steps for improved care and to generate a customised and practical guideline for managing pregnancy in women with heart disease in limited resource settings. TRIAL REGISTRATION: The TNPHDR is registered under Clinical Trials Registry-India ( CTRI/2020/01/022736 ).

Race, Ethnicity, Hypertension, and Heart Disease: JACC Focus Seminar 1/9.

Hypertension is the leading cause of cardiovascular morbidity and mortality globally. In the United States, the prevalence of hypertension (blood pressure ≥130/80 mm Hg) among adults is approximately 45%. Racial/ethnic disparities in hypertension prevalence are well documented, especially among Black adults who are disproportionately affected and have one of the highest rates of hypertension globally. Hypertension control remains a persistent public health crisis. Recently published data indicate suboptimal hypertension control rates, particularly for racial/ethnic minority groups in the United States. This requires urgent action because of the significant health care burden from cardiovascular- and stroke-related morbidity and mortality. This clinical review delineates racial/ethnic disparities in the epidemiology of hypertension, and the impact of social determinants of health on the quality of cardiovascular care and outcomes. Clinical practice guideline recommendations and various national programs targeted toward hypertension control and proposed solutions to eliminate these disparities are discussed.

Prevalence of cardiac pathology and relation to mortality in a multiethnic population hospitalised with COVID-19.

OBJECTIVE: To determine the prevalence of cardiac abnormalities and their relationship to markers of myocardial injury and mortality in patients admitted to hospital with COVID-19. METHODS: A retrospective and prospective observational study of inpatients referred for transthoracic echocardiography for suspected cardiac pathology due to COVID-19 within a London NHS Trust. Echocardiograms were performed to assess left ventricular (LV), right ventricular (RV) and pulmonary variables along with collection of patient demographics, comorbid conditions, blood biomarkers and outcomes. RESULT: In the predominant non-white (72%) population, RV dysfunction was the primary cardiac abnormality noted in 50% of patients, with RV fractional area change <35% being the most common marker of this RV dysfunction. By comparison, LV systolic dysfunction occurred in 18% of patients. RV dysfunction was associated with LV systolic dysfunction and the presence of a D-shaped LV throughout the cardiac cycle (marker of significant pulmonary artery hypertension). LV systolic dysfunction (p=0.002, HR 3.82, 95% CI 1.624 to 8.982), pulmonary valve acceleration time (p=0.024, HR 0.98, 95% CI 0.964 to 0.997)-marker of increased pulmonary vascular resistance, age (p=0.047, HR 1.027, 95% CI 1.000 to 1.055) and an episode of tachycardia measured from admission to time of echo (p=0.004, HR 6.183, 95% CI 1.772 to 21.575) were independently associated with mortality. CONCLUSIONS: In this predominantly non-white population hospitalised with COVID-19, the most common cardiac pathology was RV dysfunction which is associated with both LV systolic dysfunction and elevated pulmonary artery pressure. The latter two, not RV dysfunction, were associated with mortality.

Heart Disease, Advanced Age, Minority Race, and Hispanic Ethnicity Are Associated With Mortality in COVID-19 Patients.

BACKGROUND: The objective of this study was to determine the associations between heart disease, obesity, and demographic factors and increased COVID-19 mortality. METHODS: We extracted deidentified patient-level data from the Froedtert Health System and Children's Hospital of Wisconsin and used descriptive statistics and multivariable logistic regression to characterize relationships between heart disease, obesity, age group, sex, race and ethnicity and mortality following COVID-19 diagnosis. RESULTS: We found heart disease (adjusted odds ratio [AOR] 2.85; 95% CI, 2.11-8.83) and other demographic factors are significant predictors of increased mortality in COVID-19 patients. However, obesity was not a significant predictor of mortality (AOR 1.04; 95% CI, 0.53- 3.10). DISCUSSION: These unique results indicate some comorbid conditions and patient demographics contribute more strongly to mortality in COVID-19 patients.

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals.

Importance: Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined. Objective: To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. Design, Setting, and Participants: This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. Main Outcomes and Measures: The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. Results: The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. Conclusions and Relevance: In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.

Racial and Ethnic Disparities in Heart and Cerebrovascular Disease Deaths During the COVID-19 Pandemic in the United States.

BACKGROUND: Cardiovascular deaths increased during the early phase of the COVID-19 pandemic in the United States. However, it is unclear whether diverse racial/ethnic populations have experienced a disproportionate rise in heart disease and cerebrovascular disease deaths. METHODS: We used the National Center for Health Statistics to identify heart disease and cerebrovascular disease deaths for non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic individuals from March to August 2020 (pandemic period), as well as for the corresponding months in 2019 (historical control). We determined the age- and sex-standardized deaths per million by race/ethnicity for each year. We then fit a modified Poisson model with robust SEs to compare change in deaths by race/ethnicity for each condition in 2020 versus 2019. RESULTS: There were a total of 339 076 heart disease and 76 767 cerebrovascular disease deaths from March through August 2020, compared with 321 218 and 72 190 deaths during the same months in 2019. Heart disease deaths increased during the pandemic in 2020, compared with the corresponding period in 2019, for non-Hispanic White (age-sex standardized deaths per million, 1234.2 versus 1208.7; risk ratio for death [RR], 1.02 [95% CI, 1.02-1.03]), non-Hispanic Black (1783.7 versus 1503.8; RR, 1.19 [95% CI, 1.17-1.20]), non-Hispanic Asian (685.7 versus 577.4; RR, 1.19 [95% CI, 1.15-1.22]), and Hispanic (968.5 versus 820.4; RR, 1.18 [95% CI, 1.16-1.20]) populations. Cerebrovascular disease deaths also increased for non-Hispanic White (268.7 versus 258.2; RR, 1.04 [95% CI, 1.03-1.05]), non-Hispanic Black (430.7 versus 379.7; RR, 1.13 [95% CI, 1.10-1.17]), non-Hispanic Asian (236.5 versus 207.4; RR, 1.15 [95% CI, 1.09-1.21]), and Hispanic (264.4 versus 235.9; RR, 1.12 [95% CI, 1.08-1.16]) populations. For both heart disease and cerebrovascular disease deaths, Black, Asian, and Hispanic populations experienced a larger relative increase in deaths than the non-Hispanic White population (interaction term, P<0.001). CONCLUSIONS: During the COVID-19 pandemic in the United States, Black, Hispanic, and Asian populations experienced a disproportionate rise in deaths caused by heart disease and cerebrovascular disease, suggesting that these groups have been most impacted by the indirect effects of the pandemic. Public health and policy strategies are needed to mitigate the short- and long-term adverse effects of the pandemic on the cardiovascular health of diverse populations.

Comparison of 20-Year Obesity-Associated Cancer Mortality Trends With Heart Disease Mortality Trends in the US.

Importance: Heart disease and cancer are the 2 major diseases associated with mortality risk in the United States. Four decades of improvements in heart disease mortality slowed after 2011; this slowing has been associated with the obesity epidemic. The same pattern has not been observed for total cancer mortality. However, trends in total cancer mortality may obscure patterns specific to obesity-associated cancers. Objective: To investigate whether trends in obesity-associated cancer mortality mirror the slowed mortality improvements observed for heart disease associated with the obesity epidemic. Design, Setting, and Participants: This cross-sectional study compared US mortality trends for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision-defined cancer (total cancer, obesity-associated cancer, and cancer not associated with obesity) and heart disease deaths from January 1, 1999, to December 31, 2018. Data were included on decedents with complete information on the underlying cause of death, age, sex, race, and ethnicity. Exposures: Changes in age-adjusted cause-specific mortality rates between 1999-2011 and 2011-2018 were compared. Main Outcomes and Measures: Annual relative rates of change in age-adjusted mortality rates (AAMRs) in the overall population and stratified by sex, race, and ethnicity were estimated using Poisson regression. Differences in AAMR annual relative rates of change before and after 2011 were evaluated using Wald tests. Results: A total of 50 163 483 decedents met the inclusion criteria (50.1% female decedents, 79.9% non-Hispanic White decedents, and 11.7% non-Hispanic Black decedents; mean [SD] age, 72.8 [18.5] years). In contrast with heart disease mortality, for which improvements slowed between 1999-2011 and 2011-2018, decreases in total cancer AAMR relative change accelerated between 1999-2011 (-1.48 [95% CI, -1.43 to -1.52]) and 2011-2018 (-1.77 [95% CI, -1.67 to -1.86]) (P < .001). For obesity-associated cancer mortality, which accounted for approximately 33% of total cancer deaths annually, decreases in annual AAMR relative change decelerated from -1.19 (95% CI, -1.13 to -1.26) in 1999-2011 to -0.83 (95% CI, -0.70 to -0.96) in 2011-2018 (P < .001). The largest decelerations in obesity-associated cancer mortality were observed for female decedents (-1.45 [95% CI, -1.36 to -1.53] in 1999-2011 and -0.91 [95% CI, -0.75 to -1.07] in 2011-2018; P < .001) and non-Hispanic White individuals (-1.16 [95% CI, -1.09 to -1.22] in 1999-2011 and -0.68 [95% CI, -0.55 to -0.81] in 2011-2018; P < .001). Conclusions and Relevance: Slowing improvements in obesity-associated cancer mortality were obscured when considering total cancer mortality. These findings potentially signal a changing profile of cancer-associated mortality that may parallel trends previously observed for heart disease as the consequences of the obesity epidemic are understood.

An Aboriginal and Torres Strait Islander Cardiac Rehabilitation program delivered in a non-Indigenous health service (Yeddung Gauar): a mixed methods feasibility study.

BACKGROUND: There is limited evidence of Aboriginal and Torres Strait Islander people attending cardiac rehabilitation (CR) programs despite high levels of heart disease. One key enabler for CR attendance is a culturally safe program. This study evaluates improving access for Aboriginal and Torres Strait Islander women to attend a CR program in a non-Indigenous health service, alongside improving health workforce cultural safety. METHODS: An 18-week mixed-methods feasibility study was conducted, with weekly flexible CR sessions delivered by a multidisciplinary team and an Aboriginal and/or Torres Strait Islander Health Worker (AHW) at a university health centre. Aboriginal and Torres Strait Islander women who were at risk of, or had experienced, a cardiac event were recruited. Data was collected from participants at baseline, and at every sixth-session attended, including measures of disease risk, quality-of-life, exercise capacity and anxiety and depression. Cultural awareness training was provided for health professionals before the program commenced. Assessment of health professionals' cultural awareness pre- and post-program was evaluated using a questionnaire (n = 18). Qualitative data from participants (n = 3), the AHW, health professionals (n = 4) and referrers (n = 4) was collected at the end of the program using yarning methodology and analysed thematically using Charmaz's constant comparative approach. RESULTS: Eight referrals were received for the CR program and four Aboriginal women attended the program, aged from 24 to 68 years. Adherence to the weekly sessions ranged from 65 to 100%. At the program's conclusion, there was a significant change in health professionals' perception of social policies implemented to 'improve' Aboriginal people, and self-reported changes in health professionals' behaviours and skills. Themes were identified for recruitment, participants, health professionals and program delivery, with cultural safety enveloping all areas. Trust was a major theme for recruitment and adherence of participants. The AHW was a key enabler of cultural authenticity, and the flexibility of the program contributed greatly to participant perceptions of cultural safety. Barriers for attendance were not unique to this population. CONCLUSION: The flexible CR program in a non-Indigenous service provided a culturally safe environment for Aboriginal women but referrals were low. Importantly, the combination of cultural awareness training and participation in the program delivery improved health professionals' confidence in working with Aboriginal people. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) 12618000581268, http://www.ANZCTR.org.au/ACTRN12618000581268.aspx , registered 16 April 2018.

Adverse Trends in Premature Cardiometabolic Mortality in the United States, 1999 to 2018.

Background Life expectancy in the United States has recently declined, in part attributable to premature cardiometabolic mortality. We characterized national trends in premature cardiometabolic mortality, overall, and by race-sex groups. Methods and Results Using death certificates from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research, we quantified premature deaths (<65 years of age) from heart disease, cerebrovascular disease, and diabetes mellitus from 1999 to 2018. We calculated age-adjusted mortality rates (AAMRs) and years of potential life lost (YPLL) from each cardiometabolic cause occurring at <65 years of age. We used Joinpoint regression to identify an inflection point in overall cardiometabolic AAMR trends. Average annual percent change in AAMRs and YPLL was quantified before and after the identified inflection point. From 1999 to 2018, annual premature deaths from heart disease (117 880 to 128 832), cerebrovascular disease (18 765 to 20 565), and diabetes mellitus (16 553 to 24 758) as an underlying cause of death increased. By 2018, 19.7% of all heart disease deaths, 13.9% of all cerebrovascular disease deaths, and 29.1% of all diabetes mellitus deaths were premature. AAMRs and YPLL from heart disease and cerebrovascular disease declined until the inflection point identified in 2011, then remained unchanged through 2018. Conversely, AAMRs and YPLL from diabetes mellitus did not change through 2011, then increased through 2018. Black men and women had higher AAMRs and greater YPLL for each cardiometabolic cause compared with White men and women, respectively. Conclusions Over one-fifth of cardiometabolic deaths occurred at <65 years of age. Recent stagnation in cardiometabolic AAMRs and YPLL are compounded by persistent racial disparities.

Dose-dependent Cardiac Dysfunction and Structural Damage in Rats after Shortwave Radiation.

OBJECTIVE: To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment. METHODS: One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm 2 for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca 2+, glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy. RESULTS: The results showed that the 5, 10, and 30 mW/cm 2 shortwave radiation caused a significant increased in the levels of Ca 2+, AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation. CONCLUSION: Shortwave radiation of 5, 10, and 30 mW/cm 2 can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm 2 induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.

Heterogeneous trends in burden of heart disease mortality by subtypes in the United States, 1999-2018: observational analysis of vital statistics.

OBJECTIVE: To describe trends in the burden of mortality due to subtypes of heart disease from 1999 to 2018 to inform targeted prevention strategies and reduce disparities. DESIGN: Serial cross sectional analysis of cause specific heart disease mortality rates using national death certificate data in the overall population as well as stratified by race-sex, age, and geography. SETTING: United States, 1999-2018. PARTICIPANTS: 12.9 million decedents from total heart disease (49% women, 12% black, and 19% <65 years old). MAIN OUTCOME MEASURES: Age adjusted mortality rates (AAMR) and years of potential life lost (YPLL) for each heart disease subtype, and respective mean annual percentage change. RESULTS: Deaths from total heart disease fell from 752 192 to 596 577 between 1999 and 2011, and then increased to 655 381 in 2018. From 1999 to 2018, the proportion of total deaths from heart disease attributed to ischemic heart disease decreased from 73% to 56%, while the proportion attributed to heart failure increased from 8% to 13% and the proportion attributed to hypertensive heart disease increased from 4% to 9%. Among heart disease subtypes, AAMR was consistently highest for ischemic heart disease in all subgroups (race-sex, age, and region). After 2011, AAMR for heart failure and hypertensive heart disease increased at a faster rate than for other subtypes. The fastest increases in heart failure mortality were in black men (mean annual percentage change 4.9%, 95% confidence interval 4.0% to 5.8%), whereas the fastest increases in hypertensive heart disease occurred in white men (6.3%, 4.9% to 9.4%). The burden of years of potential life lost was greatest from ischemic heart disease, but black-white disparities were driven by heart failure and hypertensive heart disease. Deaths from heart disease in 2018 resulted in approximately 3.8 million potential years of life lost. CONCLUSIONS: Trends in AAMR and years of potential life lost for ischemic heart disease have decelerated since 2011. For almost all other subtypes of heart disease, AAMR and years of potential life lost became stagnant or increased. Heart failure and hypertensive heart disease account for the greatest increases in premature deaths and the largest black-white disparities and have offset declines in ischemic heart disease. Early and targeted primary and secondary prevention and control of risk factors for heart disease, with a focus on groups at high risk, are needed to avoid these suboptimal trends beginning earlier in life.

Effect of An Online Physical Activity Promotion Program and Cardiovascular Symptoms Among Asian American Women at Midlife.

Despite an increasing number of online programs to promote physical activity, they have rarely been evaluated for their effects on cardiovascular symptoms of racial/ethnic minority women at midlife. This study aimed to determine the preliminary efficacy of a newly developed online program for physical activity promotion on cardiovascular symptoms of Asian American midlife women. This study was a pilot repeated-measures randomized controlled trial (pretest/posttest) among 26 Asian American midlife women. The variables were measured using multiple instruments on background features, physical activity, and cardiovascular symptoms at three points of time (baseline, after 1 month, and after 3 months). Linear mixed models were used to analyze the data. The prevalence and severity of cardiovascular symptoms did not show a statistically significant group-time interaction. However, the increase in lifestyle physical activity over time was significant only among the intervention group (Δ = 0.49, P = .016). The results supported the program's preliminary efficacy on lifestyle physical activity for Asian American women at midlife, but not on cardiovascular symptoms.

Description of a large cohort of Caucasian patients with V122I ATTRv amyloidosis: Neurological and cardiological features.

V122I is one of more than 130 mutations in transthyretin gene associated with hereditary TTR (ATTRv) amyloidosis. Main clinical expression is an infiltrative pseudohypertrophic cardiomyopathy with mild or no neurological symptoms. It is particularly common among African-Americans (prevalence: 3%-4%). We report 12 subjects from seven unrelated Caucasian families hailing from Sicily and carrying the V122I mutation. One patient was homozygous for V122I and in another family two subjects also carried the E89Q variant in compound heterozygosity. All the subjects underwent neurologic/neurophysiologic evaluation and cardiologic baseline tests; in five of them, cardiac magnetic resonance and/or (99 m) Tc-DPD scintigraphy were performed. Three of 12 subjects were asymptomatic carriers. Of the remaining nine subjects, in four of nine patients, the nerve conduction studies revealed a polyneuropathy; in one of them, this represents the only sign of disease after 5 years of follow-up. In eight of nine subjects, we found a hypertrophic restrictive cardiomyopathy and cardiac failure, associated with a carpal tunnel syndrome. Although in non-Afro-American individuals V122I prevalence is low, subjects carrying this mutation have been identified in the United Kingdom, Italy, and France. Our report describes a large cohort of V122I Caucasian patients from a non-endemic area, confirming the possible underestimation of this mutation in the non-African population. Moreover, it highlights the heterogeneity in the genotype-phenotype correlation of ATTRv mutations, suggesting that the presence of a polyneuropathy has to be identified as soon as possible, since available treatments are, in Europe, so far authorized only for ATTRv amyloid peripheral neuropathy.

Change in quality of life over eight years in a nationally representative sample of US adults with heart disease and type 2 diabetes:minority race and toxic stress as keysocial determinants.

BACKGROUND: Toxic stress (TS), minority race and their interaction are evaluated as determinants of change in quality of life (QOL) over 8 years follow-up in a nationally representative sample of United States (US) adults (≥50 years old) with heart disease (HD) and/or type-2 diabetes (T2DM) diagnosed by 2006 as part of the Health and Retirement Study (HRS). METHODS: Recent and life-course stress plus experiences of lifetime discrimination were measured every 2 years using the stressful life experiences questionnaire. QOL was assessed by participant self-rated health (SRH) and operationally defined as improved, unchanged or declined in current year versus two years prior. Repeated measures multinomial logistic regressionusing generalized estimating equations (GEEs) was implemented to estimate race-, TS and their interaction- related odds of worse SRH from2006-2014. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with adjustment for time, age, sex and socio-economic status. RESULTS: Three thousand nine hundred four adults with HD/T2DM, mean age 71.1 ± 9.3 years old, 80.9, 14.7 and 4.4% that respectively self-identified as Caucasian, African-American and Other race, were included. Over the eight-year follow-up, the odds of worse SRH for African-American and Other race were respectively 1.46 (95% CI: 1.25-1.70) and 1.43 (95% CI, 1.10-1.86) times higher relative to Caucasians. Relative to older Americans that reported ≥2 lifetime discrimination events, the odds of poor SRH was respectively 33% (OR = 0.67, 95%CI: 0.50-0.89) and 17% (OR = 0.83, 95%CI: 0.59-1.17) lower for those that reported none vs one lifetime discrimination experience. Furthermore, the relationship of life-course stress to SRH decline over 8 years varied by race (time*stress*race, p = 0.1173). Specifically, increasing life-course stress predicted worse QOL among Caucasians (p = 0.0063) and among African-American (p = 0.0820) but not among Other race (p = 0.9943). CONCLUSION: Toxic stress and minority race are social determinants of deterioration in QOL among older Americans with chronic diseases (HD/T2DM). The types and prevalence of toxic stressors varied by race/ethnicity. Policy interventions to address root causes of TS while targeted at proximate drivers of TS by race/ethnicity represent a viable strategy for mitigating racial disparities in overall wellbeing and improving QOL in all aging Americans regardless of race.

Pathogenic and Uncertain Genetic Variants Have Clinical Cardiac Correlates in Diverse Biobank Participants.

Background Genome sequencing coupled with electronic heath record data can uncover medically important genetic variation. Interpretation of rare genetic variation and its role in mediating cardiovascular phenotypes is confounded by variants of uncertain significance. Methods and Results We analyzed the whole genome sequence of 900 racially and ethnically diverse biobank participants selected from a single US center. Participants were equally divided among European, African, Hispanic, and mixed races/ethnicities. We evaluated the American College of Medical Genetics and Genomics medically actionable list of 59 genes, focusing on the cardiac genes. Variation was interpreted using the most recent reports in ClinVar, a database of medically relevant human variation. We identified 19 individuals with pathogenic or likely pathogenic variants in cardiac actionable genes (2%) and found evidence of related clinical correlates in the electronic health record. Participants of African ancestry, compared with those of European ancestry, had more variants of uncertain significance in the medically actionable genes including the 30 cardiac actionable genes, even when normalized to total variant count per person. Longitudinal measures of left ventricle size from ≈400 biobank participants (1723 patient-years) were correlated with genetic findings. The presence of ≥1 uncertain variant in the actionable cardiac genes and a cardiomyopathy diagnosis correlated with increased left ventricular internal diameter in diastole and in systole. In particular, MYBPC3 was identified as a gene with excess variants of uncertain significance. Conclusions These data indicate that a subset of uncertain genetic variants may confer risk and should not be considered benign.

Racial Disparity in Cardiac Surgery Risk and Outcome: Report From a Statewide Quality Initiative.

BACKGROUND: Racial disparities persist in health care. Our study objective was to evaluate racial disparity in cardiac surgery in Maryland. METHODS: A statewide database was used to identify patients. Demographics, comorbidities, and predicted risk of death were compared between races. Crude mortality and incidence of complications were compared between groups, as were risk-adjusted odds for mortality and major morbidity or mortality. RESULTS: The study included 23,094 patients. Most patients were white (75.8%), followed by African American (16.3%), Asian (3.8%), and other races (4.1%). African Americans had a higher preoperative risk for mortality based on The Society of Thoracic Surgeons predictive models compared with white patients (3.0% vs 2.3%, P < .001). African Americans also had higher prevalence of diabetes mellitus, hypertension, peripheral vascular disease, and cerebral vascular disease than white patients. After adjustment for preoperative risk, there was no difference in 30-day mortality between African Americans (odds ratio [OR], 1.26; 95% confidence interval [CI], 0.99-1.59), Asians (OR, 1.22; 95% CI, 0.75-1.97), and other races (OR, 1.18; 95% CI, 0.74-1.89) compared with whites. African Americans had lower risk-adjusted odds of major morbidity or mortality compared with whites (OR, 0.83; 95% CI, 0.75-0.93). CONCLUSIONS: African American cardiac surgical patients have the highest preoperative risk in Maryland. Patients appeared to receive excellent cardiac surgical care, regardless of race, as risk-adjusted mortality did not differ between groups, and African American patients had lower risk-adjusted odds of major morbidity or mortality than white patients. Future interventions in Maryland should be aimed at reducing preoperative risk disparity in cardiac surgical patients.