Early-onset Hypertension Research Articles

Characteristics of patients with autosomal polycystic kidney disease reaching kidney failure by age 40.

Autosomal dominant polycystic kidney disease (ADPKD) demonstrates broad genetic and phenotypic variability, with kidney failure (KF) occurring across a wide age spectrum. Despite several predictor tools, there remains a need to identify factors associated with rapid disease progression. This study describes the phenotypic characteristics of a multicentric cohort experiencing early-onset KF by age 40. This retrospective, multicenter cohort study analyzed longitudinal data of rapidly progressive ADPKD patients (n = 199). The prevalence of established risk factors was compared to nine existing ADPKD cohorts (ntotal = 6782) with KF after 40years of age. We examined the longitudinal impact of early hypertension and urological events on the risk of developing KF. The median age at ADPKD diagnosis was 22.3years (IQR, 16.5-28.6) and median age of KF was 35.6years (31.7-38.0). Hypertension was observed in 68.1% of cases, with early-onset hypertension being more common among those with accelerated progression towards KF. Urological events were present in 60.1% of cases, with a high burden of gross hematuria (30.4%). Existing ADPKD cohorts had a mean age of 45.5years, with weighted prevalences of hypertension (71.1%), kidney stones (22.4%), hematuria (22.9%), and urinary tract infections (22.8%). Extrarenal manifestations were less prevalent compared to other ADPKD cohorts. This study outlines a cohort of ADPKD patients with accelerated disease progression, reaching KF before age 40. Hypertension and urological events were highly prevalent at a young age, emphasizing the importance of early and regular blood pressure monitoring.

Integrated Use of Autosomal Dominant Polycystic Kidney Disease Prediction Tools for Risk Prognostication.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure. Specific treatment is indicated upon observed or predicted rapid progression. For the latter, risk stratification tools have been developed independently based on either total kidney volume or genotyping as well as clinical variables. This study aimed to improve risk prediction by combining both imaging and clinical-genetic scores. We conducted a retrospective multi-center cohort study of 468 patients diagnosed with ADPKD. Clinical, imaging, and genetic data were analyzed for risk prediction. We defined rapid disease progression as an estimated glomerular filtration rate (eGFR) slope ≥3 ml/min/1.73m2/year over two years, Mayo imaging classification (MIC) 1D-1E, or a Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score of ≥7 points. Using MIC, PROPKD, and Rare Exome Variant Ensemble Learner (REVEL) scores, several combined models were designed to develop a new classification with improved risk stratification. Primary endpoints were the development of advanced chronic kidney disease (aCKD) stages G4-G5, longitudinal changes in eGFR, and clinical variables such as hypertension or urological events. Statistically, logistic regression, survival, Receiver Operating Characteristic (ROC) analyses, linear mixed models, and Cox proportional hazards models were used. PKD1-genotype (p <0.001), MIC class 1E (p <0.001), early-onset hypertension (p <0.001) and early-onset urological events (p =0.003) correlated best with rapid progression in multivariable analysis. While the MIC showed satisfactory specificity (77%), the PROPKD was more sensitive (59%). Among individuals with an intermediate risk in one of the scores, integration of the other score (combined scoring) allowed for more accurate stratification. The combined use of both risk scores was associated with higher ability to identify rapid progressors and resulted in a better stratification, notably among intermediate risk patients.

Effects of Cacna1d D307G Mutation on Blood Pressure and Kidney Function in Rats with Salt Loading

Introduction: Our recent findings revealed that CACNA1D D307G mutation participates in the early-onset hypertension. Methods: We used the CRISPR/Cas9 technique to generate the Cacna1d D307G mutation rat model and investigated the effects of Cacna1d D307G mutation on blood pressure (BP) and renal function. Rats fed normal-salt diet had normal plasma aldosterone levels but higher plasma ET-1 and mildly elevated systolic BP (SBP) in D307G and G307G rats compared with the wild type (WT) until 24 weeks. Renal function and renal histopathology did not significantly differ among the three groups. Results: When fed high-salt diet (HSD), D307G and G307G rats showed more sensitivity to HSD. The results showed a further increase in SBP than in WT rats. Plasma and vascular endothelin-1 (ET-1) level and cortex and renal artery endothelin type A (ETA) receptor protein expression were significantly increased. Enhanced renal injury was also noted as indicated by an increased ratio of kidney weight/body weight, elevated urinary protein and albumin/creatinine ratio, higher kidney injury molecule-1 (KIM-1) levels, advanced fibrosis and apoptosis, and inflammation. Further experiments revealed a reduction in urinary sodium excretion and creatinine clearance. Higher protein expression of renal cortex epithelial sodium channel α subunit (αENaC) was confirmed in D307G and G307G rats fed HSD. However, a selective ETA receptor blockade (ABT-627) could partially reverse the increased SBP, increased serum KIM-1 level, upregulated renal cortex protein expression of αENaC, and reduced urinary sodium excretion with reduced creatinine clearance in D307G rats fed HSD. Conclusion: Activation of the ET-1/ETA system in D307G mutation rats might have contributed to increased sensitivity to salt loading, augmented hypertension, and exacerbated the renal injury.

Modifiable lifestyle factors in the primordial prevention of hypertension in three US cohorts

BackgroundEvidence is lacking on the relative contributions of specific lifestyle factors and their overall contribution to prevention of hypertension, in particular early-onset hypertension. MethodsThis prospective cohort study included participants of the Nurses’ Health Study (NHS, N = 52,780 women, aged 40–67 in 1986), the NHS II (N = 83,871 women, aged 27–46 in 1991), and the Health Professionals Follow-up Study (HPFS, N = 31,269 men, aged 40–75 in 1986), who were free from hypertension, cardiovascular disease and cancer at baseline. Four modifiable lifestyles were evaluated based on hypertension guidelines: BMI, moderate-to-vigorous physical activity, Dietary Approaches to Stop Hypertension (DASH) score, and alcohol intake. Primary outcome was incident self-reported diagnosis of hypertension with 27–31 years of follow-up. ResultsEach lifestyle factor was associated with incident hypertension in dose-dependent manners across the cohorts, with BMI having the strongest associations. On average, adhering to BMI <25 kg/m2 was associated with 20.3 [18.5, 22.0], 25.0 [23.2, 26.8], and 18.6 [16.7, 20.7] months longer periods free from hypertension during 25-year follow-up in each cohort respectively. BMI accounted for approximately 20 % of incident hypertension in NHS and HPFS, and 35 % of early-onset hypertension (age < 55 y). Moderate-to-vigorous physical activity and diet accounted for 10–15 % of incident hypertension in women, and the contributions were greater for early-onset hypertension. ConclusionHealthy weight during adulthood was most substantially associated with incident hypertension among lifestyle factors, but diet, physical activity, and alcohol intake were also related to the risk across all ages, and hypertension-free periods, with stronger associations in early-onset hypertension.

The Influence of Non-Dipping Pattern of Blood Pressure in Gestational Hypertension on Early Onset of Hypertension Later in Life-Single Center Experience in Very-High-Risk Southeast and Central European Country.

Gestational hypertension (GH) and preeclampsia (PE) are associated with the onset of hypertension. This study aimed to investigate whether the blood pressure (BP) pattern in GH is associated with the prevalence of hypertension later in life. In this prospective cohort study pregnant women screened for GH underwent medical history, laboratory analysis, ambulatory blood pressure monitoring (AMBP), and transthoracic echocardiography (with left ventricular global longitudinal strain (LVGLS)) assessment. Overall, 138 GH (67 non-dippers and 71 dippers), 55 preeclamptic, and 72 normotensive pregnant controls were included. Women were followed in the postpartum period, first after 6 weeks and later on, for the occurrence of hypertension. The median follow-up was 8.97 years (8.23; 9.03). Non-dippers and PE compared with normotensives and dippers had a higher prevalence of hypertension onset (p < 0.01), as well as significantly reduced absolute values of LVGLS during pregnancy, after delivery, and at the time of onset of hypertension during follow-up (p < 0.01). Night-time diastolic BP, LVGLS, age, and left ventricular ejection fraction were the strongest predictors of postpartum onset of hypertension. The non-dipping BP pattern in GH was significantly associated with the onset of hypertension later in life, as well as with decreased systolic function.

Liddle Syndrome in a Family Presenting with Early-Onset Hypertension, Sudden Death, and Bilateral Kidney Cysts

Liddle Syndrome in a Family Presenting with Early-Onset Hypertension, Sudden Death, and Bilateral Kidney Cysts

Abstract MP22: Association between 2,5-dimethylfuran exposure and the risk of early-onset hypertension: evidence from NHANES data

Objective: This study aimed to investigate the relationship between exposure to volatile organic compounds (VOCs) and the prevalence of early-onset hypertension (EHT) within the US population. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) was utilized for this cross-sectional analysis. Weighted logistic regression models, adjusted for potential confounding variables, were employed to determine the association between blood VOC concentrations and EHT prevalence. The combined impact of exposure to multiple VOCs was assessed using weighted quantile sum (WQS) regression analysis. Results: Statistically significant, independent associations were observed between elevated blood VOC concentrations and increased EHT prevalence. Each unit increase in the WQS index was associated with a 91% increased risk of EHT (Odds Ratio [OR]: 1.82, 95% Confidence Interval [CI]: 1.54-2.16, P &lt; 0.01). Among the VOCs studied, 2,5-dimethylfuran demonstrated the highest weight in the WQS model. Restricted cubic spline analysis revealed a linear, positive correlation between blood 2,5-dimethylfuran levels and EHT probability, with the risk of EHT increasing by 37% (OR: 1.37, 95% CI: 1.18-1.59) for each additional unit (10 -1 ng/mL) of 2,5-dimethylfuran. This association between 2,5-dimethylfuran exposure and EHT remained consistent across various statistical models and demographic subgroups, with more pronounced effects observed in individuals with lower body mass index and smokers. Conclusion: This study highlights the potential role of 2,5-dimethylfuran exposure in the development of EHT. These findings emphasize the need to consider 2,5-dimethylfuran exposure in public health initiatives aimed at mitigating the rising prevalence of EHT. Further research is warranted to elucidate the underlying mechanisms of this association and investigate the long-term health consequences of 2,5-dimethylfuran exposure in young adults.

Abstract P155: Elevated Long-Term Triglyceride-to-High Density Lipoprotein Cholesterol Ratio Variability From Childhood Is Linked To Higher Risk Of Early-Onset Hypertension: The Bogalusa Heart Study

Background: Early-onset hypertension is linked to higher risk of hypertensive organ damage compared to late-onset hypertension. Insulin resistance has been shown to be associated with greater risk of hypertension. Greater triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL-C), a surrogate marker of insulin resistance, has been linked to higher risk of hypertension. However, whether elevated long-term TG/HDL-C variability from childhood is associated with higher risk of early-onset hypertension is unclear. Methods: We studied 1271 participants of the Bogalusa Heart Study (age at enrollment: 9.9 ± 4.0 years, follow-up : 38.3 ± 3.8 years, age at last exam: 48.2 ± 5.2 years, 59.5% women, 34.4% Black participants) with ≥3 lipid measurements during follow-up. TG/HDL-C was obtained as TG (mg/dL) divided by HDL-C (mg/dL). Onset of hypertension was defined as blood pressure ≥140/90 mmHg or taking antihypertensive medications detected during follow-up. According to age at onset of hypertension, 4 subgroups were formed: &lt;35 years (early-onset hypertension), 35-44 years, ≥45 years, and people without hypertension. Long-term TG/HDL-C variability from childhood was calculated as the deviation from age predicted values (DEV) and residual SD (RSD). DEV and RSD were obtained from the growth curves derived from linear mixed effect models, as the mean and SD of the residuals of observed and predicted TG/HDL-C levels. Associations between TG/HDL-C variability and hypertension onset subgroups were evaluated using multinomial logistic regression models. People who did not have hypertension during follow-up were the reference group. Interactions by race and sex were performed. Results: Among the 1271 participants, 585 (46.0%) had hypertension at last exam; among the 585, 124 (21.2%) had early-onset hypertension. For 1 SD increase in DEV and RSD of TG/HDL-C, the odds of early-onset hypertension increased by 30.6% (95% CI 1.06, 1.61) and 28.8% (95% CI 1.06,1.57), compared to people without hypertension, after adjusting for race, sex, diabetes, obesity, and smoking status, education, and TG/HDL-C at last exam. No significant associations were observed between DEV and RSD of TG/HDL-C and other hypertension onset subgroups. No significant interactions were found between both DEV and RSD and race and sex. Conclusions: Our results suggest that individuals with higher long-term variability in insulin resistance may be at a greater risk of having early-onset hypertension.

Abstract P372: Greater Long-Term Non-High Density Lipoprotein Cholesterol Variability From Childhood Is Associated With Higher Risk Of Early-Onset Hypertension: The Bogalusa Heart Study

Background: Early-onset hypertension is associated with greater risk of cardiovascular mortality and hypertension associated organ damage, compared to late-onset hypertension. Non-high-density lipoprotein cholesterol (non-HDL-C) is known to better predict future cardiovascular event risk, compared to low-density lipoprotein cholesterol. Whether higher long-term non-HDL-C variability from childhood is associated with higher risk of early-onset hypertension is unclear. Methods: We included 1271 participants of the Bogalusa Heart Study (age at enrollment: 9.9 ± 4.0 years, follow-up: 38.3 ± 3.8 years, age at last exam: 48.2 ± 5.2 years, 59.5 % women, 34.4 % Black participants) with ≥3 lipid measurements during follow-up. Non-HDL-C was calculated as total cholesterol (mg/dL) - HDL-C (mg/dL). Onset of hypertension was defined as having blood pressure ≥140/90 mmHg or using antihypertensive medications during follow-up. Participants were categorized according to age at hypertension onset (years) into 4 subgroups: &lt;35 (early-onset), 35-44, ≥45, and people without hypertension. Long-term non-HDL-C variability was obtained from the deviation from age predicted values (DEV) and residual SD (RSD). DEV and RSD were calculated from growth curves derived from linear mixed effect models, as the mean and SD of the residuals of observed and predicted non-HDL-C levels. Associations between non-HDL-C variability and hypertension onset subgroups were analyzed using multinomial logistic regression models. Interactions by race and sex were performed. Results: For 1-SD increase in DEV and RSD of non-HDL-C, the odds of hypertension increased for all hypertension onset subgroups compared to people without hypertension, after adjusting for race, sex, diabetes, obesity, and smoking status, education, and non-HDL-C at last exam. The odds of hypertension was highest in the early-onset subgroup (Table). No significant interactions were found between both DEV and RSD and race and sex. Conclusions: Our findings suggest that individuals with higher long-term non-HDL-C variability may be at a greater risk of having early-onset hypertension.

Abstract P425: Role of 24h UNaK ratio in patients with hypertension and resistant hypertension by gender and race

RHTN is defined as blood pressure above goal despite using ≥3 antihypertensive medications. Patients with RHTN are at an increased risk for CVD compared to those with more easily controlled hypertension (HTN). High sodium intake and higher 24h urinary (U) sodium (Na) potassium(K) ratio is associated with higher CVD risk. The role of this ratio in RHTN has not been investigated. Methods: We conducted a cross-sectional analysis of a large cohort of 2397 black and white patients with RHTN who were referred to the RHTN Clinic at the University of Alabama at Birmingham and who underwent a 24h urine collection. Patients with HTN served as a control group. Results: Patients with RHTN had significantly higher 24h UNaK ratio than patients with HTN (3.2±1.6 vs 3.6 ±2.0, p &lt;0.001 ) and had an earlier onset of HTN (38.8±13.7 years (yrs) vs 47.6±16.2 yrs, p=0.001) and longer duration 17.6±11.2 vs 12.0±10.7 yrs, p=0.001), higher BMI (32.6±7.2 vs 29.98±6.5 kg/m2), and 24-hourUNa (181±88 vs 164±77 mmol, p=0.01). Within the RHTN group (n=1340) females had a significant higher 24h UNaK ratio than males (3.5±1.9 vs 3.2±1.7, p =0.006) and blacks had a significant higher 24h UNaK ratio than whites (3.0±1.6 vs 3.9±2.0, p&lt;0.001). Conclusion: Higher 24h UNaK ratio as index of higher sodium and lower potassium intakes were found in patients with RHTN as well as resistant hypertensive females and blacks and may explain certain higher CV risks in these populations.

Abstract P218: Resistant hypertension is associated with elevated 24-hour cortisol to cortisone ratios in black patients.

Background: RHTN is defined as blood pressure above goal despite using ≥3 antihypertensive medications. Patients with RHTN are at an increased risk for cardiovascular (CVD) compared to those with more easily controlled hypertension (HTN). Blacks With RHTN are at a specifically high risk for CVD. Mineralocorticoid receptor activation has been found as an important mechanism of RHTN. However, aldosterone levels are not different in blacks versus whites. The role of 24-hour cortisol-to-cortisone ratios in this group has not been investigated. Methods: We conducted a cross-sectional analysis of a large cohort of 2397 black and white patients with RHTN who were referred to the RHTN Clinic at the University of Alabama at Birmingham and who underwent 24-hour urine collection including cortisol and cortisone. Patients with HTN served as a control group. Results: Black patients with RHTN compared to whites had a trend to higher 24h cortisol levels (17.7±27.6 vs 16.9±14.9, p =0.70, significantly lower 24h cortisone levels (60.45±37.7 vs 75.3±40.0, p 0.000234), and significantly higher 24h cortisol-to-cortisone ratios (0.23±0.14 vs 0.20 ±0.10, p=0.027). They were younger (53.3±11.6 vs 59.4±12.9 years), more obese (BMI 34.9±7.6 vs 30.8±6.1 kg/m2, p&lt;0.001), had earlier onset of HTN (35.6±12.5 vs 41.4±11.6 years of age, p&lt;0.001), higher 24-hour urinary sodium excretion (188.2±92.5 vs 174.9±83.1 mmol, p=0.006) and lower potassium excretion (54.5 ±28.6 vs 65.5 ±30.5 mmol, p&lt;0.001). Furthermore, they had a significantly higher rate of heart failure (p=0.000455) and diabetes (p=0.0006). Conclusion: Cortisol dysregulation and a higher cortisol-to-cortisone ratio as an index of 11beta HSD2 activity may play a role in black patients with RHTN and may be related to adverse outcomes in this population.

Abstract P219: Risk factors for Accelerated Vascular Aging in Resistant Hypertension: Should we screen our patients earlier?

Background: There is an increase in Cardiovascular disease(CVD) mortality rates among young adults worldwide. Patients with resistant hypertension (RHTN) are at particularly high risk for CVD compared to those with more easily controlled hypertension (HTN). RHTN is defined as blood pressure above goal despite using ≥3 antihypertensive medications. The role of accelerated vascular aging (AVA) in this group has not been well investigated. Our study aims to evaluate risk factors for AVA and its role in RHTN. Methods: We conducted a cross-sectional analysis of a large cohort of 965 black and white patients with RHTN referred to the RHTN Clinic at the University of Alabama at Birmingham. Patients with HTN served as a control group. Results: The most compelling data was seen in young patients (age 41-55 yrs). Those with RHTN had significantly higher arterial stiffness than patients with HTN (pulse pressure: 63.3±17.9 vs 51.2 ±11.7 mm Hg, p=&lt;0.001) earlier onset of HTN (34.2 ±7.3 vs 39.4±10.3 yrs, p=0.001) and longer duration (15.5±9.6 vs 10.7±9.0 yrs, p=0.001), higher BMI (35.4±8.3 vs 31.9±6.6 kg/m2), higher Aldosterone Renin Ratio (12.4±13.2 vs 7.9±12.9, p=0.026), and 24-hour urinary sodium excretion (217.2±104.6 vs 182.8±77.2 mmol, p=0.036). Conclusion: Younger patients with RHTN, when compared with HTN, seem to have AVA as evidenced by higher prevalance of obesity, arterial stiffness, overactivation of the renin-angiotensin-aldosterone system, and higher salt intake. Earlier screening, starting at the age of 35 yrs, may help detect AVA quicker and prevent complications associated with RHTN in younger adults

P059 IDENTIFYING PREDICTORS OF EARLY-ONSET HYPERTENSION IN MIDDLE-AGED INDIVIDUALS WITH OBESITY

Background: Hypertension is a leading risk factor for cardiovascular diseases, with obesity being one of its primary modifiable predictors. This longitudinal study aims to identify early predictors of developing hypertension in middle-aged individuals with obesity, contributing to targeted prevention strategies. Methods: A cohort of 112 middle-aged participants (mean age 48.6 ± 10.8 years, 55% male) with a body mass index (BMI) ≥ 30 kg/m^2 but without hypertension at baseline were followed for an average of 5.8 ± 2.4 years. The study sought to determine significant predictors for the development of hypertension, including demographic variables, lifestyle factors, and biochemical markers. Cox proportional hazards regression models were employed to estimate hazard ratios (HR) for the development of hypertension, with Kaplan-Meier analysis used to visualize time-to-event outcomes. Statistical significance was determined by p-values &lt; 0.05. Results: Over the follow-up period, 34% of participants developed hypertension. Kaplan-Meier analysis indicated a significant difference in hypertension-free outcomes based on baseline insulin resistance levels and waist-to-hip ratio (WHR) (p &lt; 0.01). Cox regression analysis revealed that insulin resistance (HR = 1.12 per unit increase, 95% CI: 1.06-1.19, p = 0.001) and WHR (HR = 2.48 for the highest quartile vs. lowest, 95% CI: 1.32-4.67, p = 0.005) were independent predictors of developing hypertension. Furthermore, a sedentary lifestyle was associated with an increased risk (HR = 1.89, 95% CI: 1.01-3.54, p = 0.046), whereas dietary factors did not show a significant relationship after adjusting for other variables. Conclusion: This study identifies insulin resistance and WHR as significant predictors of early-onset hypertension among middle-aged individuals with obesity, with lifestyle factors also playing a crucial role. These findings underscore the importance of targeted interventions focusing on reducing insulin resistance and central obesity, along with promoting physical activity, to prevent the development of hypertension in this high-risk population.

#395 Gut dysbiosis in ADPKD patients: a controlled pilot study

Abstract Background and Aims Gut dysbiosis has been associated with chronic kidney disease (CKD) and nephrolithiasis and may thus be a factor explaining variability of outcome in autosomal dominant polycystic kidney disease (ADPKD). However, beside a single pilot study the gut microbiome has not been studied in ADPKD. Due to the implications of microbiota in inflammation and crystal formation, we hypothesized that gut dysbiosis could also negatively affect PKD. For this reason, we aimed to characterize the intestinal microbiome in a controlled pilot study of PKD patients and explore the potential impact of dysbiosis on PKD disease progression. Method This study was designed as an observational, cross-sectional controlled pilot study. 25 ADPKD patients were recruited from the AD(H)PKD patient cohort. 12 healthy control subjects were age- and sex matched. Patients with chronic bowel disease were excluded. Serum parameters including eGFR were analyzed around the timepoint of stool collection. The gut microbiome was analyzed by 16S rRNA gene profiling of stool samples. The sequencing data was processed using the DADA2 pipeline and QIIME version 2. Differentially abundant features were identified using linear discriminant analysis (LDA) effect size (LEfSe) analysis. Bacteria-derived serum uremic toxins (total and free Trimethylaminoxid, Indoxylsulfate, p-Cresyl-Sulfate) were measured using liquid chromatography coupled to tandem mass spectrometry (LC- MS/MS). Microbiome data was then correlated with age, kidney function, and markers of PKD disease progression like Mayo classification and early onset of arterial hypertension or urologic complications (&amp;lt;35 years of age). Results Healthy control subjects revealed a significantly higher abundance Actinobacteria (LEfSe LDA score = 3.9, p = 0.025) including probiotic Bifidobacteriaceae (LEfSe LDA score = 3.9, p = 0.021). ADPKD patients displayed a significantly increased abundance of potentially dysbiotic Enterobacteriaceae (LEfSe LDA score = 3.6, p = 0.009). Those findings were independent of kidney function. Most notably, the abundance of Streptococcaceae were significantly overrepresented in PKD patients with Mayo Classes 1D and 1E compared to 1A-1C (p = 0.011). Additionally, early onset of hypertension (&amp;lt; 35 years of age) was associated with an increased abundance of potentially dysbiotic Proteobacteria and a decreased abundance of potentially probiotic Tannerelleaceae. Furthermore, ADPKD patients revealed increased abundance of Peptococcaceae with increasing age and declining kidney function. Finally, serum uremic toxins were significantly increased in ADPKD patients and highly correlated with eGFR. Serum uremic toxins revealed a tendency of positive correlation with the abundance of Peptococcaceae which did not reach statistical significance. Conclusion This controlled pilot study confirms alterations of specific OTUs in PKD patients showing an increase of Enterobacteriaceae and decrease of probiotic Bifidobacteriaceae upon PKD. This suggests a potential shift towards gut dysbiosis. Most notably, the abundance of specific OTUs were observed to be associated with markers of rapid disease progression like Mayo classification 1D and 1E, as well as early onset of arterial hypertension. This suggests for the first time, that gut dysbiosis could affect PKD disease progression. However, it still remains unknown whether gut dysbiosis is caused by ADPKD itself or is a consequence of secondary circumstances such as antibiotic treatment which is common in ADPKD due to frequent urinary tract or cyst infections. Thus, further investigation in larger cohorts is warranted to elucidate the impact of gut microbiota on ADPKD.

#2961 Association of polygenic risk scores for blood pressure with incidence of hypertension and chronic kidney disease

Abstract Background and Aims Genetic risk for elevated blood pressure (BP) has been associated with a higher risk of hypertension and cardiovascular disease. However, the generalizability of previous findings has been limited due to a lack of studies among Asian populations. This study aimed to investigate whether genetic risk for BP predicts the incidence of hypertension and chronic kidney disease (CKD) in Asian populations. Method We performed genome-wide association studies for systolic and diastolic BP (SBP and DBP, respectively) using data from the Korean Genome and Epidemiology Study (KoGES). We then meta-analyzed these results with summary statistics from Biobank Japan to construct polygenic risk scores (PRSs) and examined the association between BP PRSs and incident hypertension or CKD. This study included participants without hypertension, cardiovascular disease, or CKD at baseline (n=4349, median age 48.5 years, 48.8% men). Participants were categorized into four groups based on their PRS percentile (&amp;lt;5, 5–50, 50–95, &amp;gt;95). Results As the PRS percentile increases, the median SBP and DBP at baseline also increase. Compared to the lowest SBP PRS percentile, higher PRS percentile was associated with increased risk of hypertension (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.22–1.83 for PRS percentile 5–50, HR 1.94, 95% CI 1.58–2.38 for PRS percentile 50–95, and HR 2.35, 95% CI 1.80–3.07 for PRS percentile &amp;gt;95). Elevated DBP PRS was also associated with higher risk of hypertension (HR 1.27, 95% CI 1.04–1.54 for PRS percentile 5–50, HR 1.72, 95% CI 1.41–2.09 for PRS percentile 50-95, and HR 2.09, 95% CI 1.60–2.72 for PRS percentile &amp;gt;95). The highest PRS percentile for SBP and DBP was associated with earlier onsets of hypertension by median 11 and 9 years, respectively, compared to the lowest PRS percentile for SBP and DBP. However, both SBP and DBP RPSs were not associated with incident CKD. Conclusion Genetic risk for elevated BP was associated with a higher risk of incident hypertension and earlier onset of hypertension in the Asian population. However, there was no association between PRS for elevated BP and the incidence of CKD.

A Rare Case of Apparent Mineralocorticoid Excess Presenting as Endocrine Hypertension

A 3-year-old boy presented with polyuria and polydipsia for 18 months, along with growth failure. He was born prematurely, at 34 weeks of gestation, with a low birth weight. On examination, the child was severely underweight and hypertensive. Clinical history and evaluation could not identify any secondary causes of hypertension. There was no significant family history. An endocrine workup was planned, considering hypokalemia and metabolic alkalosis. This demonstrated hyporeninemic hypoaldosteronism and raised the possibility of apparent mineralocorticoid excess (AME) and Liddle syndrome. Clinical exome sequence analysis of HSD11B2 revealed a homozygous mutation in exon 5 (911A&gt;G; p.His304Arg), which resulted in a missense mutation that confirmed the diagnosis of AME. A novel homozygous variant was found in the HSD11B2 gene in a subject with early onset hypertension associated with hypokalemic metabolic alkalosis, establishing the diagnosis of AME.

Prediction of various insulin resistance indices for the risk of hypertension among military young adults: the CHIEF cohort study, 2014–2020

BackgroundNon-insulin-based insulin resistance (NI-IR) indices have been reported to have an association with prevalent hypertension, however, no cohort studies to date have compared their prediction of hypertension among young adults.MethodsA total of 2,448 military men and women, aged 18–39 years, without baseline hypertension in Taiwan were followed for incident hypertension events from 2014 until the end of 2020. All subjects underwent annual health examinations including measurements of blood pressure (BP) in mmHg. Systolic BP (SBP) 130–139/diastolic BP (DBP) < 80, SBP < 130/DBP 80–89, and SBP 130–139/DBP 80–89 were respectively defined as stage I isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and combined hypertension (CH). The cut-off levels of stage II hypertension for SBP and DBP were 140–159 and 90–99, respectively. Four NI-IR indices included the ratio of serum triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C), TyG index defined as ln[TG* fasting glucose (FG)/2], Metabolic Score for IR (METS-IR) defined as ln[(2* FG) + TG)* body mass index (BMI)/(ln(HDL-C))], and ZJU index defined as BMI + FG + TG + 3* alanine transaminase/aspartate transaminase (+ 2 if female). Multivariable Cox regression analysis was performed with adjustments for baseline age, sex, body mass index, BP, substance use, family history for early onset cardiovascular diseases or hypertension, low-density lipoprotein cholesterol, kidney function, serum uric acid and physical activity to determine the associations.ResultsDuring a median follow-up of 6.0 years, there were 920 hypertension events (37.6%). Greater TyG, TG/HDL-C and METS-IR indices were associated with a higher risk of stage I IDH (hazard ratios (HRs) and 95% confidence intervals: 1.376 (1.123–1.687), 1.082 (1.039–1.127) and 3.455 (1.921–6.214), respectively), whereas only greater ZJU index was associated with a higher risk of stage II IDH [HRs: 1.011 (1.001–1.021)]. In addition, greater ZJU index was associated with a higher risk of stage II ISH [HR: 1.013 (1.003–1.023)], and greater TyG index was associated with a higher risk of stage II CH [HR: 2.821 (1.244–6.395)].ConclusionInsulin resistance assessed by various NI-IR indices was associated with a higher risk of hypertension in young adults, while the assessment ability for specific hypertension category may differ by NI-IR indices.

Early-Onset Hypertension and Sex-Specific Residual Risk for Cardiovascular Disease in Type 2 Diabetes.

To investigate whether the sex disparities in type 2 diabetes-associated cardiovascular disease (CVD) risks may be related to early-onset hypertension that could benefit from intensive blood pressure (BP) control. We analyzed intensive versus standard BP control in relation to incident CVD events in women and men with type 2 diabetes, based on their age of hypertension diagnosis. Among 3,792 adults with type 2 diabetes (49% women), multivariable-adjusted CVD risk was increased per decade earlier age at hypertension diagnosis (hazard ratio 1.11 [1.03-1.21], P = 0.006). Excess risk associated with early-diagnosed hypertension was attenuated in the presence of intensive versus standard antihypertensive therapy in women (P = 0.036) but not men (P = 0.76). Women with type 2 diabetes and early-onset hypertension may represent a higher-risk subpopulation that not only contributes to the excess in diabetes-related CVD risk for women but may benefit from intensive BP control.

Abstract HUP20: Early Onset Hypertension Increases Risk Of Midlife Stroke Among Black Women

Background: Stroke at midlife contributes to earlier mortality and greater disability. There is a critical lack of data about early life stroke risk factors among Black women, a group with higher rates of hypertension compared to other racial groups. The hypothesis of the study is that early onset hypertension increases risk of midlife stroke among Black women. Methods: The Black Women’s Health Study is a prospective study of 59000 Black women from across the US who were followed since 1995. Baseline year for this analysis was the 1999 questionnaire. We included stroke-free participants younger than age 65 (46754 participants, mean age 42±9.6 [range 24-64] years). History of hypertension was determined by self-report, defined as physician-diagnosed hypertension with use of an antihypertensive medication or diuretic, or use of an antihypertensive alone. Ischemic and hemorrhagic stroke were ascertained by self-report at biennial health questionnaires. Using Cox models, we estimated risk of midlife stroke, comparing persons with and without hypertension before age 45, between ages 45-64, and at 10-year age intervals. Follow up was from 1999 until whichever came first: incident stroke, death, loss to follow-up, or end of study follow-up (12/31/19). Results: At baseline, 2980 (10.5%) of participants age &lt;45 and 7147 (38.7%) of participants between ages 45-64 had hypertension. Stroke occurred in 1485 participants (3.2%) during up to 23 years of follow up (mean 17.1±5.0 years). Compared to women with no history of hypertension, Black women with hypertension before age 45 had a higher risk of midlife stroke (HR=2.23, 95% CI=1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes. Risk was also increased with hypertension at midlife age 45-64 (HR=1.69, 95% CI=1.47-1.95) and was highest among those with hypertension at age 24-34 (HR=3.15, 95% CI=1.92-5.16). Conclusion: Black women with hypertension before age 45 have more than twice the risk of stroke at midlife and hypertension before age 35 more than triples the risk. The findings are important to inform public health interventions to expand hypertension screening and treatment in this high-risk population.

Abstract 101: Early Onset Hypertension Increases Risk of Midlife Stroke Among Black Women

Background: Stroke at midlife contributes to earlier mortality and greater disability. There is a critical lack of data about early life stroke risk factors among Black women, a group with higher rates of hypertension compared to other racial groups. The hypothesis of the study is that early onset hypertension increases risk of midlife stroke among Black women. Methods: The Black Women’s Health Study is a prospective study of 59000 Black women from across the US who were followed since 1995. Baseline year for this analysis was the 1999 questionnaire. We included stroke-free participants younger than age 65 (46754 participants, mean age 42±9.6 [range 24-64] years). History of hypertension was determined by self-report, defined as physician-diagnosed hypertension with use of an antihypertensive medication or diuretic, or use of an antihypertensive alone. Ischemic and hemorrhagic stroke were ascertained by self-report at biennial health questionnaires. Using Cox models, we estimated risk of midlife stroke, comparing persons with and without hypertension before age 45, between ages 45-64, and at 10-year age intervals. Follow up was from 1999 until whichever came first: incident stroke, death, loss to follow-up, or end of study follow-up (Dec 31, 2019). Results: At baseline, 2980 (10.5%) of participants age &lt;45 and 7147 (38.7%) of participants between ages 45-64 had hypertension. Stroke occurred in 1485 participants (3.2%) during up to 23 years of follow up (mean 17.1±5.0 years). Compared to women with no history of hypertension, Black women with hypertension before age 45 had a higher risk of midlife stroke (HR=2.23, 95% CI=1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes. Risk was also increased with hypertension at midlife age 45-64 (HR=1.69, 95% CI=1.47-1.95) and was highest among those with hypertension at age 24-34 (HR=3.15, 95% CI=1.92-5.16). Conclusion: Black women with hypertension before age 45 have more than twice the risk of stroke at midlife and hypertension before age 35 more than triples the risk. The findings are important to inform public health interventions to expand hypertension screening and treatment in this high-risk population.