Hypertension In Cohort Research Articles

Validation of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from UK Biobank

BackgroundCurrently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, in which 10% 10-year CVD risk indicates clinical intervention. However, this benchmark has limited efficacy in clinical practice and the need for a more simple, non-invasive risk stratification tool is necessary. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aims to further validate our biomarker, Reti-CVD, (1) to detect risk group of ≥ 10% in 10-year CVD risk and (2) enhance risk assessment in individuals with QRISK3 of 7.5–10% (termed as borderline-QRISK3 group) using the UK Biobank.MethodsReti-CVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of Reti-CVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding Reti-CVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups.ResultsAmong 48,260 participants with no history of CVD, 6.3% had CVD events during the 11-year follow-up. Reti-CVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.41; 95% confidence interval [CI], 1.30–1.52) with a 13.1% (95% CI, 11.7–14.6%) 10-year CVD risk in Reti-CVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in Reti-CVD-high-risk group (11.5% in non-statin cohort [n = 45,473], 11.5% in stage 1 hypertension cohort [n = 11,966], and 14.2% in middle-aged cohort [n = 38,941]). C statistics increased by 0.014 (0.010–0.017) in non-statin cohort, 0.013 (0.007–0.019) in stage 1 hypertension cohort, and 0.023 (0.018–0.029) in middle-aged cohort for CVD event prediction after adding Reti-CVD to QRISK3.ConclusionsReti-CVD has the potential to identify individuals with ≥ 10% 10-year CVD risk who are likely to benefit from earlier preventative CVD interventions. For borderline-QRISK3 individuals with 10-year CVD risk between 7.5 and 10%, Reti-CVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in adult groups that may be pre-disposed to CVD.

Remote physiologic monitoring for hypertension in primary care: a prospective pragmatic pilot study in electronic health records using propensity score matching.

Since 2019, the Centers for Medicare and Medicaid Services covers remote physiologic monitoring (RPM) for blood pressure (BP) per hypertension diagnosis and treatment guidelines. Here, we integrated Omron VitalSight RPM into the health system's electronic health record to transmit BP and pulse without manual entry, assessed feasibility, and used pragmatic prospective matched cohort studies to assess initial effects in (1) uncontrolled (last two office BP ≥140/90 mmHg) and (2) general (diagnosed hypertension or last office BP ≥140/90 mmHg) hypertension patient populations. Seventeen clinicians at two internal medicine practices were oriented. Eligible patients were aged 65-85 years had Medicare insurance with ≥1 office visit in the previous year. We prospectively identified matched controls (age, sex, BP, and number of office visits in previous year) from other primary care practices within the health system and estimated the association between RPM availability (clinic-level) and patient BP outcomes after 6 months. ClinicalTrials.gov: NCT04604925. Feasibility. Uptake was low at pilot clinics: 10 physicians prescribed RPM to 118 patients during the 6-month pilot. This included 7% (14/207) of the prespecified uncontrolled hypertension cohort and 3.3% (78/2356) of the general hypertension cohort. Surveyed clinicians (n = 4) reported changing their patients' medical treatment in response to RPM BPs, although they recommended having a dedicated RN or LPN to review BP readings. Effectiveness. At 6 months, BP control was greater at pilot practices than among matched controls (uncontrolled: 31.4% vs 22.8%; P = .007; general: 64.0% vs 59.7%; P < .001). Systolic BP at last office visit did not differ (mean [SD] 146.0 [15.7] vs 147.1 [15.6]; P = .48) in the uncontrolled population, and was lower in the general population (131.8 [15.7] vs 132.8 [15.9]; P = .04).The frequency of antihypertensive medication changes was similar in both groups (uncontrolled P = .986; general P = .218). Uptake notwithstanding, RPM may have improved BP control. A potential mechanism is increased physician awareness of and attention to uncontrolled hypertension. Barriers to RPM use among physicians require further study.

PS-P10-4: A NOVEL AND NONINVASIVE RISK ASSESSMENT SCORE AND ITS CHILD-TO-ADULT TRAJECTORIES TO SCREEN SUBCLINICAL RENAL DAMAGE IN MIDDLE AGE

This study aimed to develop a noninvasive, economical and effective subclinical renal damage (SRD) risk assessment tool to identify the high-risk asymptomatic people from large-scale population and improve current clinical SRD screening strategies. 2303 participants were included from Hanzhong Adolescent Hypertension Cohort, an ongoing prospective study followed for 30 years. Three noninvasive prediction factors (SBP, DBP and BMI) were identified as SRD-associated variables. Based on these three variables., an SRD risk assessment score with excellent classification ability (AUC value of ROC curve: 0.778 for SRD estimation, 0.729 for 4-year SRD risk prediction), calibration (Hosmer-Lemeshow goodness-of-fit test P = 0.62 for SRD estimation, P = 0.34 for 4-year SRD risk prediction) and more potential clinical benefits was developed. In addition, we identified three child-to-adult SRD risk assessment score trajectories: increasing, increasing-stable and stable. Further difference analysis and logistic regression analysis also showed these SRD risk assessment score trajectories were highly associated with the incidence of SRD in middle age. In brief, we developed a novel and noninvasive SRD risk assessment tool with excellent performance to help identify high-risk asymptomatic people from large-scale population and assist in SRD screening. JOURNAL/jhype/04.03/00004872-202301001-01109/figure1/v/2023-10-24T163949Z/r/image-jpeg

A Comparative Study of Left Atrial Function Index of Hypertensive Heart Failure Patients Versus Controls in a Teaching Hospital, Sub-Saharan Africa.

The left atrium contributes significantly to the left ventricular filling as it functions as a reservoir, conduit, and pump. These functions are referred to as the phasic function of the left atrium and they are assessed using left atrial volumes. The left atrial function index on the other hand is a rhythmic independent composite index which is a better marker of left atrial function. The study therefore aimed at comparing left atrial function (using the left atrial function index) among hypertensive heart failure patients, patients with hypertension but not in heart failure, and normotensive patients. The study was a cross-sectional analytical study that was carried out at Delta State University Teaching Hospital, Nigeria. A total of 80 hypertensive heart failure patients, 80 hypertensive, and 40 normotensive patients who met the inclusion criteria were recruited from the cardiology clinics using the convenience sampling method. The left atrial function index was determined using the volumetric method. Significance was assessed atp< 0.05. The left atrial function index (21.13 ± 8.83 versus 42.28 ± 10.40 versus 50.47 ± 14.37,p= 0.001) of the hypertensive heart failure group was significantly lowest when compared with the hypertensive (p< 0.001) and normotensive (p< 0.001) groups. Although the left atrial function index of the hypertensive group (42.28 ± 10.40) was lower than the normotensive group (50.47 ± 14.37), it was however not found to be significant (p= 0.12). Also, the left atrial function index was significantly (p= 0.001) worse among the patients with heart failure with reduced ejection fraction (13.5 ± 5.94) compared to heart failure with preserved ejection fraction (40.81 ± 12.12). Left atrial function index was lowest among hypertensive heart failure patients compared with hypertensive and normotensive cohorts, and it was worse among heart failure with reduced ejection fraction patients. However, there was no significant difference between the left atrial function index of the hypertensive and normotensive groups. As a result, we recommend that the left atrial function index should be incorporated into the routine echocardiographic assessment of patients in our day-to-day clinical practice and large studies should be carried out to determine the cut-off value for the left atrial function.

Risk stratification, prognosis, and survival in a pulmonary arterial hypertension cohort in Latin America. A multicenter study

BackgroundPulmonary arterial hypertension (PAH) guidelines suggest that achieving a low-risk profile should be the treatment goal. Our aim was to assess a risk assessment strategy based on three non-invasive variables from the ESC/ERS 2015 guidelines in a Latin American cohort. Methods92 incident patients (mean [SD] age 47, 77% female, 53% idiopathic PAH) were included in this retrospective, multicenter study. Patients were stratified at baseline and at early follow-up, within the first year, using three non-invasive variables (WHO functional class, 6-minute walking distance, BNP/NT-proBNP) from the ESC/ERS 2015 risk assessment instrument. Median (IQR) follow-up was 3.11 years (3.01 years). ResultsAt baseline assessment, 25% of patients were at low risk, 61.9% at intermediate-risk, and 13% at high-risk. At early follow-up (median 9.5 months), 56.5% of patients were at low-risk, 40.2% at intermediate-risk, and 3.2% at high-risk (p<0.001 vs. baseline). According to risk stratification at early follow-up, one, three and five-year overall survival was 100% in the low-risk group (no deaths at five-year follow-up), and 100%, 84% (95% CI: 72–98%), and 66% (95% CI: 48–90%) respectively in the intermediate-risk group, p = 0.0003. Mortality in the high-risk patients at early follow-up was 1/3 (33.3%). One, three, and five-year event-free survival (death or transplant or first hospitalization due to worsening PAH) based on early follow-up risk assessment was higher in the low-risk group, p = 0.0003. ConclusionOur study validates a risk assessment strategy based on three non-invasive variables and confirms that early achievement of a low-risk profile should be the treatment goal.

Long-term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort.

This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Association of Cerebrovascular Reactivity and Cognitive Performance in a Racially Diverse Cohort

AbstractBackgroundCerebrovascular reactivity (CVR) to increased carbon dioxide (CO2) reflects cerebral microvascular function and is impaired in hypertension and stroke. Limited studies have looked at its relationship with cognitive performance in African Americans and Whites.MethodsWe used data from the Brain‐Stress Hypertension and Aging Program cohort (B‐SHARP) consisting of racially diverse individuals with normal cognition or mild cognitive impairment (MCI). CVR was measured using advanced signal modeling approach developed by BH/IH during blood oxygenation level dependent (BOLD) resting state ‐fMRI. Participants underwent cognitive assessment using global and domain‐specific tests such as Montreal Cognitive Assessment (MoCA), Boston Naming Test (BNT), Hopkins Verbal Learning Test‐Revised (HVLT‐R), and Trail Making Test. We used multivariate regression models to assess the relationship of CVR and cognitive domains and tested interaction of CVR with race.ResultsSuccessful CVR data were completed on 219 participants with mean age= 65.3 years (SD 7.8), 46% African American and 65% women. An increased resting whole brain CVR was associated with a higher MoCA score (β = 6.46, SE 2.43, p‐value 0.008), higher BNT score (β =2.15, SE 0.93 p‐value 0.02), and shorter time on Trail B‐A, (β= ‐113.4, SE 42.0, p‐value 0.007) after adjusting for mean arterial pressure. After adjusting for age, sex, and race, increased resting whole brain CVR was associated with higher MoCA (β =4.4, SE 2.26, p‐value 0.05), BNT score (β =1.46, SE 0.89, p‐value 0.1) and Trail B‐A score (β =‐86.7, SE 40.3, p‐value 0.03). There was no association with delayed memory based on HVLT‐R. The results were similar for individuals with normal cognition or MCI. There was a significant interaction by race (p&lt;0.01) such that whole brain CVR was associated with better performance on all cognitive tests for African Americans but not for Whites.ConclusionsHigher CVR, reflected by resting state BOLD‐fMRI, was associated with higher overall cognitive status and specific domains including language and executive functioning in individuals with normal cognition or MCI. The differential effect in African Americans vs Whites could suggest a greater contribution of microvascular dysfunction for the higher prevalence of cognitive impairment in African Americans.

Influence of Iron Deficiency on Clinical and Haemodynamic Parameters in Pulmonary Arterial Hypertension Cohorts.

Iron deficiency (Fedef) has been shown to be common in patients with group 1 or pulmonary arterial hypertension (PAH). Several studies have shown a negative impact of Fedef on clinical and haemodynamic parameters of the disease, but data from individual studies have not been strong enough to lead to incorporation of the finding of Fedef into prognostic or therapeutic algorithms. The goal of this meta-analysis was to combine data from available studies to better define any associations between Fedef and established variables of prognostic importance in PAH. A literature search identified nine studies with extractable data relevant to the study questions. The impact of Fedef upon the following parameters was evaluated: 6-minute walk distance (6MWD), WHO-functional class, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, echocardiography, and findings from right heart catheterisation (RHC). Pooled results were reported as mean difference or risk difference with 95% confidence intervals utilising a random effects modeling approach. Fedef in the PAH population was common (47% of cases) and was associated with cardiovascular dysfunction (lower tricuspid annular plane systolic excursion [TAPSE], elevated NT-proBNP, and lower mixed venous oxygen saturation) and with reduction in functional capacity (lower 6MWD and higher functional class). This meta-analysis strengthens the relationships between Fedef and several markers of poor outcome in PAH. Fedef in patients with PAH warrants further scrutiny and merits consideration as a cause of clinical deterioration. Even though causation and longitudinal relationships between Fedef and PAH could not be identified, effect of Fedef on factors that affect disease prognosis is noteworthy and worthy of more focussed studies.

Long-Term Follow-up of Human Immunodeficiency Virus-Associated Pulmonary Hypertension: Clinical Features and Survival Outcomes of the Pan Africa Pulmonary Hypertension Cohort (PAPUCO).

Data characterizing risk factors and long-term outcome studies on human immunodeficiency virus (HIV)-associated pulmonary hypertension (PH) in Africa are lacking. The Pan African Pulmonary Hypertension Cohort, a multinational registry of 254 consecutive patients diagnosed with PH (97% of African descent) from 9 centers in 4 African countries was implemented. We compared baseline characteristics and 3-year survival of an HIV-infected cohort newly diagnosed with PH (PH/HIV+) to an HIV-uninfected cohort with PH (PH/HIV-). One hundred thirty-four participants with PH completed follow up (47 PH/HIV+ and 87 PH/HIV-; age median, 36 versus 44 years; P = .0004). Cardiovascular risk factors and comorbidities were similar except for previous tuberculosis (62% versus 18%, P < .0001). Six-minute walk distance (6MWD) <300 meters was common in PH/HIV- (P = .0030), but PH/HIV+ had higher heart (P = .0160) and respiratory (P = .0374) rates. Thirty-six percent of PH/HIV+ and 15% of PH/HIV- presented with pulmonary arterial hypertension (PAH) (P = .0084), whereas 36% of PH/HIV+ and 72% of PH/HIV- exhibited PH due to left heart disease (PHLHD) (P = .0009). Pulmonary hypertension due to lung diseases and hypoxia (PHLD) was frequent in PH/HIV+ (36% versus 15%) but did not reach statistical significance. Human immunodeficiency virus-associated PAH tended to have a poorer survival rate compared with PHLHD/PHLD in HIV-infected patients. The PH/HIV + patients were younger and commonly had previous tuberculosis compared to PH/HIV- patients. Despite a better 6MWD at presentation, they had more signs and symptoms of early onset heart failure and a worse survival rate. Early echocardiography assessment should be performed in HIV-infected patients with history of tuberculosis who present with signs and symptoms of heart failure or posttuberculosis lung disease.

Trends over Time in Overall Survival of Patients with Multiple Myeloma By Race/Ethnicity and By Comorbidity Status: A Surveillance, Epidemiology, and End Results (SEER)-Medicare Analysis

Introduction: New advances in multiple myeloma (MM) treatments have improved overall survival (OS), though there is uncertainty regarding the benefits of these treatments for all patients (pts) with MM. This study assessed OS trends over time in subgroups of pts with MM defined by race/ethnicity and comorbidity status. Methods: Newly diagnosed pts with MM (2007-16) in the US were identified from the SEER-Medicare database. Medicare enrollment on initial diagnosis date was required and pts with other cancers were excluded. Pt characteristics at initial diagnosis and comorbidities during the 6-month baseline period were described for pts with continuous enrollment in the baseline period. OS was described using Kaplan-Meier analysis from initial MM diagnosis to death. Trends in OS over time were evaluated by creating cohorts based on year of diagnosis (2007-09, 2010-12, and 2013-16), and log-rank tests compared OS between the cohorts. All outcomes were described separately for the following race/ethnicity subgroups: non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic (HIS) and for subgroups defined by the presence of diabetes mellitus (DM) or hypertension (HTN), two of the most common comorbidities in pts with MM, in the baseline period. Results: The study included 21,757 pts with MM. Median age at diagnosis was 75 years (range 27-101), 51% of pts were male, and mean Charlson Comorbidity Index (CCI) was 1.2. Overall, 14,077 (64.7%) were NHW, 4078 (18.7%) were NHB, and 2371 (10.9%) were HIS. At baseline, HTN (44.9%), DM (20.4%), renal disease (14.0%), lung disease (13.6%), and heart failure (11.4%) were common comorbidities not related to MM. Monoclonal gammopathy of undetermined significance was identified in 10.0% of pts overall, and in 7.6%, 9.8%, and 11.2% of the NHW, NHB, and HIS cohorts, respectively; 5.5% of pts overall were obese. Median OS was 3.26 years, OS improved significantly over time (P < 0.001 for 2007-09 vs 2010-12, 2007-09 vs 2013-16, 2010-12 vs 2013-16), and median OS increased with each time period (2007-09, 2.78 years; 2010-12, 3.16 years; 2013-16, 3.64 years) (Table 1). The NHW subgroup had a median age of 75 years, 53% male pts, and a mean CCI of 1.1. Trends over time in OS were similar to the overall sample, with P < 0.001 for all-year cohort comparisons and increasing median OS over time. The NHB subgroup had a median age of 73 years, 43% male pts, and a mean CCI of 1.5. Improvements in OS were observed relative to the oldest subgroup (2007-09 vs 2010-12, P < 0.05; 2007-09 vs 2013-16, P < 0.001), but not in the most recent year subgroups (2010-12 vs 2013-16, P = 0.125). The HIS subgroup had a median age of 74 years, 50% male pts, and a mean CCI of 1.4. There was no significant improvement in OS across year cohorts (2007-09 vs 2010-12, P = 0.163; 2007-09 vs 2013-16, P = 0.053; 2010-12 vs 2013-16, P = 0.850), although median OS increased over time (2007-09, 2.92 years; 2010-12, 3.48 years; 2013-16, 3.53 years). Among pts with MM and DM (N = 4410, 20.3%), OS improved over time relative to the oldest cohort (2007-09 vs 2010-12 and 2007-09 vs 2013-16, P < 0.01). No improvement was observed between the most recent cohorts (2010-12 vs 2013-16, P = 0.844) (Table 2). Median OS showed a similar trend (2007-09, 2.44 years; 2010-12, 2.90 years; 2013-16, 2.80 years) and was shorter than the overall population. In the HTN cohort (N = 9646, 44.3%), median OS increased over time (2007-09, 2.58 years; 2010-12: 2.79 years; 2013-16: 3.07 years), but OS showed statistically significant improvements only when comparing the oldest to the most recent cohort (2007-09 vs 2010-12, P = 0.058; 2007-09 vs 2013-16, P < 0.001; 2010-12 vs 2013-16, P = 0.081). Conclusions: Variation in OS trends over time in pts with MM was observed across subgroups. While OS improved significantly across cohorts for NHW and NHB pts, significant improvement was not seen for HIS pts. Comorbidities were common and for pts with HTN and DM, no significant improvement in OS was observed in recent years. Median OS was lower in both comorbidity cohorts compared with the total MM population. Reasons for racial disparities need to be explored further; these differences in outcomes confirm the need for equitable access to effective treatments and tailored treatments for pts with comorbidities. Additional analyses are underway assessing trends over time in gaps in survival between pts with MM and the general population for these subgroups. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 10113: Validation of a Deep-Learning-Based Retinal Biomarker in the Prediction of Cardiovascular Disease: Data From UK Biobank

Introduction: Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, with a benchmark of 10% for 10-year CVD risk determining clinical intervention. Yet, effects on clinical practice are limited and the barriers call for a simple, non-invasive risk stratification tool. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aimed to further validate our biomarker, Reti-CVD, 1) to detect risk group of ≥10% in 10-year CVD risk and 2 ) enhance risk assessment in individuals with QRISK3 of 7.5%-10% (termed as borderline-QRISK3 group) using the UK Biobank. Methods: RetiCVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of RetiCVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding RetiCVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups. Results: Among 45,233 participants with no history of CVD, 6.7% had CVD events during the 11-year follow-up. RetiCVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.34 (95% confidence interval [CI], 1.26-1.42) with a 14.7% (95% CI, 13.6-15.9%) 10-year CVD risk in RetiCVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in RetiCVD-high-risk group (12.8% in non-statin cohort [n=16240], 11.5% in stage 1 hypertension cohort [n=5102], and 14.9% in middle-aged cohort [n=11,474]). C statistics increased by 0.013 (0.010-0.017) in non-statin cohort, 0.017 (0.010-0.024) in stage 1 hypertension cohort, and 0.022 (0.017-0.027) in middle-aged cohort for CVD event prediction after adding RetiCVD to QRISK3. Conclusion: RetiCVD has the potential to identify individuals with ≥10% 10-year CVD risk who are likely to benefit from earlier, upstream preventative CVD interventions. For borderline-QRISK3 individuals, RetiCVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in early vulnerable adult groups.

Abstract 9486: miR-425/CFL2 Regulates Natriuretic Peptides Expression in Human CVD

Introduction: Previously, miR-425 have been implicated in the inhibition of the cardiac natriuretic peptide (NP) ANP gene expression with their role on BNP undefined. The mechanism by which miR-425 modulates NP expression remains to be explored. In heart failure (HF), adrenergic and neurohormone pathways are aberrantly activated. Our goal was to investigate the role of miR-425 and its downstream target Cofilin 2 (CFL2) on ANP and BNP expression in human CV disease (CVD). Hypothesis: We hypothesized miR-425, via CFL2, supresses NPs expression in vitro. MiR-425, CFL2 and NP levels were also determined in CVD patients. Methods: In vitro, human cardiomyocytes (HCM) were treated with vehicle (Veh), catecholamine isoproterenol (ISO) and cytokine endothelin (ET), miR-425 mimic. Cells were transfected with CFL2 plasmid or CFL2 siRNA. Normal (NM, n=100), Hypertension (HTN, n=30) and Acute HF (AHF, n=74) cohorts were studied. A confirmatory cohort was recruited. Plasma NT-proBNP, miR-425 were measured. In left ventricles (LV) from NM or HF (n=5 each), NP, CFL2 and miR-425 expression were assessed. Data expressed as means±SEM. * p&lt;0.05 vs NM or Veh. Results: In vitro in HCM, treatment with ISO or ET in HCM reduced miR-425 and elevated NP mRNA levels. Furthermore, miR-425 mimic reduced Nppa (Veh: 1.0±0.03, mimic: 0.7±0.02*) and Nppb levels (Veh: 1.0±0.03, mimic: 0.5±0.01*). We showed that a top predicted target of miR-425, CFL2, was also reduced by the mimic. Further, NP mRNA was elevated by CFL2 overexpression and reduced by the knockdown of CFL2. In humans, MiR-425 was lower in HTN and AHF patients (NM: 0.15±0.03, HTN: 0.03±0.005*, HF: 0.01±0.003*) than NM. MiR-425 negatively correlates with NT-proBNP in NM and AHF cohorts. Downregulation of miR-425 was validated in a second AHF cohort. Similarly, in HF LV tissues, miR-425 (NM: 2.5±0.5, HF: 1.0±0.5*) was lower than NM group, while CFL2 and NP gene and protein expression were increased. Conclusion: In vitro, cardiac stress hormones downregulate miR-425 and increase NP gene expression, potentially through a novel target, CFL2. In CVD patients, miR-425 is lower, accompanied by an elevation of CFL2 and NP. Our findings implicate the pathway of stress hormones/miR-425/CFL2/NP production in CVD.

APOL1 Genotype, Proteinuria, and the Risk of Kidney Failure: A Secondary Analysis of the AASK (African American Study of Kidney Disease and Hypertension) and CRIC (Chronic Renal Insufficiency Cohort) Studies

Patients with a high-risk Apolipoprotein L1 (APOL1) genotype are more likely to develop chronic kidney disease and kidney failure. It is unclear whether this increased risk is entirely mediated by the development of proteinuria. Retrospective observational study of the African American Study of Kidney Disease and Hypertension cohort and Chronic Renal Insufficiency Cohort. Self-identified race (Black/non-Black) and presence of high-risk APOL1 genotype. The primary model was adjusted for age, sex, diabetes, estimated glomerular filtration rate, and urinary protein-creatinine ratio. Time to kidney failure defined as time to dialysis or transplantation. We used Cox proportional hazard models to study how proteinuria mediates the association between APOL1 and kidney failure. We modeled proteinuria at baseline and as a time-varying covariate. A high-risk APOL1 genotype was associated with a significantly higher risk of kidney failure, even for patients with minimal proteinuria (HR, 1.87; 95% CI, 1.23-2.84). The association was not significant among patients with high proteinuria (HR, 1.22; 95% CI, 0.93-1.61). When modeling proteinuria as a time-varying covariate, a high-risk APOL1 genotype was associated with higher kidney failure risk even among patients who never developed proteinuria (HR, 2.04; 95% CI, 1.10-3.77). Compared to non-Black patients, Black patients without the high-risk genotype did not have higher risk of kidney failure (HR, 0.96; 95% CI, 0.85-1.10). Two datasets were combined to increase statistical power. Limited generalizability beyond the study cohorts. Residual confounding common to observational studies. A high-risk APOL1 genotype is significantly associated with increased kidney failure risk, especially among patients without baseline proteinuria. Although our results suggest that the risk is partially mediated through proteinuria, higher kidney failure risk was present even among patients who never developed proteinuria. Providers should consider screening for the high-risk APOL1 genotype, especially among Black patients without proteinuria in populations with chronic kidney disease.

261 HIGH FRACTURE RISK IN OLDER IRISH ADULT FALLERS

Abstract Background Fracture risk due to falls depends on several factors including bone density, quality and size, hip geometry (axis length), direction of fall (forward, backwards or sideways), body mass index (BMI), type of surface impacted, body site of impact and mechanism of fall (eg syncope). We aimed to identify the fracture risk per fall in frail older Irish adults. Methods Participants were from the hypertensive and cognitive cohort of the Trinity, Ulster, Dept Agriculture (TUDA) study of Irish adults (aged &amp;gt;60) recruited from hospital outpatient services and GP practises. Falls and falls resulting in fracture in the previous year were self-reported so those with an MMSE &amp;lt; 25 were excluded to avoid recall bias. We identified fallers, recurrent fallers and fractures due to falls in the previous year. Results 892 fallers, mean age 76.3 ± 8.4 yrs, 65.2% female. 23.8% had 2 falls and 24.2% ≥3 falls. Mean timed up and go was 17.3 ± 9.5 seconds. Commonest fracture due to falls were hip (20.1%), upper limb (18.5%) and lower limb (17.9%) with one fracture of neck and skull. Fracture rate per fall was 7.1%: 1.7% for hip, 1.3% for lower and 1.2% for upper limb. Annual fracture rate per faller was 16.5%. The only predictors of fall with fracture versus no fracture were female sex (OR 2.4, 1.6-3.6, P&amp;lt;0.001) and lower body mass index (P=0.001). Conclusion We identified similar hip fracture rates (1.7%) due to falls as in other studies. However, one in six fallers had sustained a fracture in the previous year reflecting the high proportion of recurrent fallers. Lower BMI and female sex predicted fall with fracture as both are strongly correlated with risk of osteoporosis. Recent guidelines now factor in recurrent falls when estimating the probability of future osteoporotic fractures.

Comparison of the efficiency between electrocardiogram and echocardiogram for left ventricular hypertrophy evaluation in patients with hypertension: Insight from the Korean Hypertension Cohort Study.

In patients with hypertension, left ventricular hypertrophy (LVH) represents a risk factor for cardiovascular disease and asymptomatic organ damage. Currently, electrocardiography (ECG) and two-dimensional echocardiography (Echo) are the most widely used methods for LVH evaluation. This study aimed to compare the long-term outcomes of LVH, as evaluated by ECG and Echo, in patients with hypertension. Patients diagnosed with hypertension as a primary disease between 2006 and 2011 were enrolled in the Korean Hypertension Cohort study. The study finally included 1743 patients who underwent both ECG and Echo. The primary endpoint was defined as the composite of major adverse cardiovascular events (MACEs) or death. Overall, LVH was identified in 747 patients. The patients were categorized into four groups according to the detection of LVH by ECG or Echo: No LVH (n=996), LVH diagnosed by ECG alone (n=181), LVH diagnosed by Echo alone (n=415), LVH diagnosed by both ECG and Echo (n=151). After adjusting for variables, the incidence of MACEs or death was significantly greater in patients with LVH diagnosed by ECG alone (hazards ratio [HR]: 1.69; 95% confidence interval [CI]: 1.22-2.35; P=.001), LVH diagnosed by Echo alone (HR: 1.54; 95% CI: 1.16-2.05; P=.002), and LVH diagnosed by both ECG and Echo (HR: 1.87; 95% CI: 1.18-2.94; P=.002) than in those with no LVH. Both ECG and Echo are efficient diagnostic tools for LVH and useful for long-term risk stratification. Additional Echo evaluation for LVH is helpful for predicting long-term outcomes only in patients without LVH diagnosis by ECG.

Pregnancy and Childbirth in Women With Idiopathic Intracranial Hypertension.

Background Idiopathic intracranial hypertension affects many women of childbearing age. However, the literature is sparse regarding pregnancy outcomes for these women. The goal of this study is to investigate the relationship between pregnancy outcomes in patients with a diagnosis of idiopathic intracranial hypertension. Methodology The TriNetX Research Network database was used to query 57 healthcare organizations for patients with idiopathic intracranial hypertension while pregnant (cohort 1) versus those who were pregnant without idiopathic intracranial hypertension (cohort 2). Cohorts were propensity-score matched for confounders related to pregnancy outcomes. The primary outcomes of interest were ectopic or molar pregnancy, cesarean section, abortion, preterm labor, depression, pre-eclampsia or eclampsia, and mortality. Chi-square analysis and logistic analysis were used on categorical variables. Results Ectopic/molar pregnancy was seen in 106 (1.75%) versus 117 (1.93%) (odds ratio (OR) 0.904, 95% confidence interval (CI) (0.694, 1.179), p = 0.4572) patients in cohorts 1 and 2, respectively. Cesarean section was seen in 785 (12.94%) versus 886 (14.59%) (OR 0.869, 95% CI (0.784, 0.964), p = 0.0078) patients, abortion in 536 (8.83%) versus 682 (11.24%) (OR 0.765, 95% CI (0.679, 0.862), p < 0.0001), preterm labor in 498 (8.206%) versus 668 (11.01%) (OR 0.723, 95% CI (0.640, 0.816), p < 0.0001), depression in 1,057 (17.42%) versus 1,061 (17.48%) (OR 0.995, 95% CI (0.906, 1.093), p = 0.9238), and pre-eclampsia/eclampsia in 501 (8.26%) versus 492 (8.11%) (OR 0.1.02, 95% CI (0.896, 1.161), p = 0.7657). Mortality was seen in 68 patients in cohort 1 versus 13 patients in cohort 2 (OR 5.279, 95% CI (2.913, 9.564), p < 0.0001). Conclusions This retrospective study examined pregnancy outcomes for pregnant women with a diagnosis of idiopathic intracranial hypertension. Women with idiopathic intracranial hypertension do not have an increase in rates of abortion, ectopic/molar pregnancy, cesarean section, preterm labor, or depression when compared to women without idiopathic intracranial hypertension. The mortality rate was higher in the idiopathic intracranial hypertension cohort, but still very low. This study demonstrates that pregnancy is generally well tolerated in the idiopathic intracranial hypertension population.

Quadratic relationship between systolic blood pressure and white matter lesions in individuals with hypertension.

There is a well documented relationship between cardiovascular risk factors and the development of brain injury, which can lead to cognitive dysfunction. Hypertension (HTN) is a condition increasing the risk of silent and symptomatic ischemic brain lesions. Although benefits of hypertension treatment are indisputable, the target blood pressure value where the possibility of tissue damage is most reduced remains under debate. Our group performed a cross-sectional ( n = 376) and longitudinal ( n = 188) study of individuals without dementia or stroke (60% women n = 228, age 68.5 ± 7.4 years; men n = 148, age 70.7 ± 6.9 years). Participants were split into hypertensive ( n = 169) and normotensive ( n = 207) groups. MR images were obtained on a 3T system. Linear modeling was performed in hypertensive and normotensive cohorts to investigate the relationship between systolic (SBP) and diastolic (DBP) blood pressure, white matter lesion (WML), and brain volumes. Participants in the hypertensive cohort showed a quadratic relationship between SBP and WML, with the lowest amounts of WML being measured in participants with readings at approximately 124 mmHg. Additionally, the hypertensive cohort also exhibited a quadratic relationship between DBP and mean hippocampal volume; participants with readings at approximately 77 mmHg showing the largest volumes. Longitudinally, all groups experienced WML growth, despite different BP trajectories, further suggesting that WML expansion may occur despite or because of BP reduction in individuals with compromised vascular system. Overall, our study suggests that in the hypertensive group there is a valley of mid-range blood pressures displaying less pathology in the brain.

Impact of COVID-19 pandemics upon nationwide pulmonary hypertension cohort: 18-months analysis of BNP-PL national database

Abstract Introduction Pulmonary hypertension (PH) patients may be vulnerable to SARS-CoV-2 infection, but large analytic studies on morbidity and mortality risks are limited. Aim Assessment of the incidence and course of COVID-19 among patients (pts) diagnosed with PH, treated under the NFZ program, registered in the national BNP-PL database with the assessment of the impact of the SARS-CoV-2 pandemic on the care of patients with pulmonary hypertension in Poland. Methods We analyzed the records of the complete population of Polish pts treated under the National Drug Program of PH (PAH and CTEPH), registered in the national database of BNP-PL, and updated on an ongoing basis by all PH centers. The frequency of SARS-CoV-2 infections, clinical severity of COVID-19 course and mortality were reviewed. Clinical characteristics of infected and deceased patients were compared to the remaining patients registered in the BNP-PL database. The rate of increase of new diagnoses ended with inclusion in the Drug Program between 01 March 2020 and 31 August 2021, compared to the pre-pandemic year 2019, and the change in the treatment profile were reviewed. Results The analysis included 1923 pts (PAH 1292, CTEPH 631). The incidence of SARS-CoV-2 infections was 7.4% (n=143) and similar to general population (7.6%), with a slight preponderance in PAH 8.1% (n=105) vs. CTEPH 6.0% (n=38) (p=0.099). 47 patients (33%) required hospitalization. Mortality rate was 24% (34/143) vs. 2.6% for general population – including 19/34 outside of hospital. Those who died due to COVID-19 were older (mean age 56±17.6 vs. 70.5±12.8 yrs; p&amp;lt;0.0001) and had more cardiovascular comorbidities (1.35 vs. 1.97; p=0.01). Systemic arterial hypertension was the strongest unique risk factor for mortality, present in 71% decedents vs. 45% of survivors, and the only independent risk factor in multivariate logistic regression analysis (OR 2.94, 95% CI 1.28–6.73). Moreover, there was a trend towards a higher incidence of diabetes and coronary artery disease in the group of non-survivors (Table 1). The number of new diagnoses of PH decreased during the pandemic compared to 2019 (new diagnoses rate in 2019 was 28.2/month vs. 19.2/month during COVID). A significant increase in total mortality was also observed in the PH group (11.1/month in 2019 vs. 13.7/month during COVID). Escalation of specific PH therapy also reduced (rate of specific therapy escalation in 2019 was 30.4/month vs. 20.5/month during COVID). Conclusions The COVID-19 pandemic has deeply affected the care of patients with pulmonary hypertension by reducing the number of new diagnoses, escalation of therapy, and increasing overall mortality in this population, and this impact continues into second year of pandemics. Pulmonary hypertension is associated with a more severe course and higher mortality in COVID-19. Funding Acknowledgement Type of funding sources: None.

Blood pressure control measures and cardiovascular outcomes: a prospective hypertensive cohort

Purpose We investigated whether blood pressure (BP) control measures, visit-to-visit BP variability, and time in therapeutic range (TTR) are associated with future cardiovascular outcomes in hypertensive patients. Materials and Methods Among 1,408 hypertensive patients without cardiovascular disease, we prospectively evaluated the incident major cardiovascular events over 6 years. In newly diagnosed patients, antihypertensive drug treatment was initiated. We estimated two markers of on-treatment BP control, (1) visit-to-visit BPV as the coefficient of variation of office systolic BP (BP-CV), and (2) TTR calculated as the percentage of office systolic BP measurements within 120–140mmHg across visits. Results The hypertensive cohort (672 males, mean age 60 years, 31% newly diagnosed) had a mean systolic/diastolic BP of 142/87 mmHg. The mean number of visits was 4.9 ± 2.6, while the mean attained systolic/diastolic BP during follow-up was 137/79 mmHg using 2.7 ± 1.1 antihypertensive drugs. The BP-CV and TTR were 9.1 ± 4.1% and 45 ± 29%, respectively, and the incidence of the composite outcome was 8.3% (n = 117). After adjustment for relevant confounders and standardization to z-scores, BP-CV and TTR were associated with a 43% (95% CI, 27–62%) increase and a 33% (95% CI, 15–47%) reduction in the outcome. However, the joint evaluation of TTR and BP-CV in a common multivariable model indicated that a standardized change of TTR was associated with the outcome to a greater extent than BP-CV (mean hazard ratios of 30% vs. 24%, respectively). When combined with the higher BP standardized-CV quartile, the lower TTR quartile predicted the outcome by 2.3 times (95% CI, 1.1–5.4) compared to the inverse TTR and BP-CV quartile pattern. Conclusion High BP-CV or low TTR was associated with future cardiovascular events in a cohort of treated hypertensive patients. As a determinant, the extent of TTR value appears greater than BP-CV when these measures are considered in the same multivariable model.

Clinical event reductions in high-risk patients after renal denervation projected from the global SYMPLICITY registry.

Renal denervation has been shown to lower blood pressure in sham-controlled trials and represents a device-based treatment option for hypertension. We sought to project clinical event reductions after radiofrequency renal denervation using a novel modelling approach. The Global SYMPLICITY Registry is a global, prospective all-comer registry to evaluate safety and efficacy after renal denervation. For this analysis, change in office systolic blood pressure from baseline was calculated from reported follow-up in the Global SYMPLICITY Registry. Relative risks for death and other cardiovascular events as well as numbers needed to treat for event avoidance were obtained for the respective blood pressure reductions based on previously reported meta-regression analyses for the full cohort and high-risk subgroups including type 2 diabetes, chronic kidney disease, resistant hypertension, and high basal cardiovascular risk. Average baseline office systolic blood pressure and reduction estimates for the full cohort (N=2651) were 166±25 and -14.8±0.4mmHg, respectively. Mean reductions in blood pressure ranged from -11.0--21.8mmHg for the studied high-risk subgroups. Projected relative risks ranged from 0.57 for stroke in the resistant hypertension cohort to 0.92 for death in the diabetes cohort. Significant absolute reductions in major adverse cardiovascular events over 3 years compared with the projected control (8.6 ± 0.7% observed vs. 11.7 ± 0.9% for projected control; P<0.01) were primarily due to reduced stroke incidence. The robustness of findings was confirmed in sensitivity and scenario analyses. Model-based projections suggest radiofrequency renal denervation for patients with uncontrolled hypertension adds considerable clinical benefit across a spectrum of different cohort characteristics.