Abstract 432: Race Differences in the Relationship between Urinary ET-1 and BP-related Target Organ Damage in Youth

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Gregory A Harshfield ◽  
Gregory A Harshfield ◽  
Jennifer Pollock ◽  
David Pollock

The overall goal of this study was to determine race/ethnic differences in the associations between renal ET-1 and indices of blood pressure-related target organ damage in healthy adolescents. The subjects ranged in age between 15-19 years, had no history of any disease, and were not on any prescription medications. The 92 subjects consisted of 48 Caucasians (CA) and 44 African-Americans (AA). The two groups were similar with respect to height, weight, body mass index, blood pressure, ET-1), albumin excretion rate (AER), and left ventricular mass). Results: The CA’s were slightly older 17±1 v 16±1 (p=.02). The protocol was preceded by a 3 day self-selected sodium controlled diet of 250 mEq/day day which the subject picked up each day. The test day began with an echocardiogram for the assessment of left ventricular mass. Next, the subjects were seated for 60 minutes of rest during which the subjects consumed 200 ml of water. This was followed by the collection of a urine sample for the measurement of ET-1 and AER. Overall, ET-1 excretion was correlated with AER (r=.278), LV mass/ht 2.7 (r=.341), and systolic blood pressure (SBP; r=.365; p=.01 for each). The significant overall correlations were the result of significant correlations in AAs for AER (r=.344; p=.05), LV mass/ht 2.7 (r=.520; p=.01), and SBP (r=.645; p=.01) which were not apparent in CA’s. These findings suggest urinary ET-1 contributes to the development of BP-related target organ damage in AA youths prior to the development of increases in blood pressure.

2018 ◽  
Vol 25 (15) ◽  
pp. 1587-1595 ◽  
Author(s):  
Michél Strauss ◽  
Wayne Smith ◽  
Ruan Kruger ◽  
Wen Wei ◽  
Olga V Fedorova ◽  
...  

Background The endogenous steroidal inhibitor of sodium–potassium-dependent adenosine triphosphate and natriuretic hormone, marinobufagenin, plays a physiological role in ionic homeostasis. Animal models suggest that elevated marinobufagenin adversely associates with cardiac and renal, structural and functional alterations. It remains uncertain whether marinobufagenin relates to the early stages of target organ damage development, especially in young adults without cardiovascular disease. We therefore explored whether elevated 24-hour urinary marinobufagenin excretion was related to indices of subclinical target organ damage in young healthy adults. Design This cross-sectional study included 711 participants from the African-PREDICT study (black 51%, men 42%, 24.8 ± 3.02 years). Methods We assessed cardiac geometry and function by two-dimensional echocardiography and pulse wave Doppler imaging. 24-Hour urinary marinobufagenin and sodium excretion were measured, and the estimated glomerular filtration rate determined. Results Across marinobufagenin excretion quartiles, left ventricular mass ( P < 0.001), end diastolic volume ( P < 0.001), stroke volume ( P = 0.004) and sodium excretion ( P < 0.001) were higher within the fourth compared with the first quartile. Partial regression analyses indicated that left ventricular mass ( r = 0.08, P = 0.043), end diastolic volume ( r = 0.10, P = 0.010) and stroke volume ( r = 0.09, P = 0.022) were positively related to marinobufagenin excretion. In multivariate-adjusted regression analysis, left ventricular mass associated positively with marinobufagenin excretion only in the highest marinobufagenin excretion quartile (adjusted R2 = 0.20; β = 0.15; P = 0.043). This relationship between left ventricular mass and marinobufagenin excretion was evident in women (adjusted R2 = 0.06; β = 0.127; P = 0.015) but not in men (adjusted R2 = 0.06; β = 0.007; P = 0.92). Conclusions Left ventricular mass positively and independently associates with marinobufagenin excretion in young healthy adults with excessively high marinobufagenin excretion. Women may be more sensitive to the effects of marinobufagenin on early structural cardiac changes.


2011 ◽  
Vol 119 (1) ◽  
pp. c27-c34 ◽  
Author(s):  
Eirini Andrikou ◽  
Costas Tsioufis ◽  
Kyriakos Dimitriadis ◽  
Dimitrios Flessas ◽  
Vagelis Chatzistamatiou ◽  
...  

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Gilad Hamdani ◽  
Michael A Ferguson ◽  
Marc B Lande ◽  
Kevin Meyers ◽  
Mark Mitsnefes ◽  
...  

Ambulatory BP (ABP) is increasingly used to confirm the diagnosis of hypertension. Pediatric but not adult guidelines consider BP load (% readings above 95 th %ile) in risk-stratification of the ABP phenotype. We compared ABP sex- and height- specific percentile and BP load as predictors of left ventricular hypertrophy (LVH) in youth. We measured casual BP, ABP, anthropometrics, and calculated LV mass by echo as (g)/height (m) 2.7 (LVMI) in 357 adolescents (mean age 15.5 + 1.7 years, 63% white, 59% male). ABPM was performed with the Ontrak device (Spacelabs Inc., Snoqualmie, WA). ABP index was defined as mean ABP/sex- and height-specific 95 th %ile. LVH was defined as LVMI ≥38.6 (pediatric cut-point). Logistic regression was used to assess different ABP measures as predictors of LVH. Sensitivity and specificity of different ABP cut points as predictors of LVH were calculated. Seventy (19.6%) participants had LVH. Systolic 24-hour, wake and sleep ABP indices as well as 24-hour SBP load were all significantly associated with LVH, while wake and sleep SBP load were not. When adjusted for BMI percentile and sex, only the associations between ABP indices and LVH remained statistically significant (table). SBP percentiles also had better balanced sensitivities and specificities in predicting LVH (24-hour 65 th percentile: 63% and 59%; wake 70 th percentile: 54% and 62%; sleep 75 th percentile: 60% and 61%). There was no significant association between diastolic BP measures and LVH. We conclude that there is no significant contribution of BP load in predicting LVH in youth. Systolic ABP percentiles lower than the commonly used 95 th percentile are the best predictors of LVH in this population.


Author(s):  
Federica Nista ◽  
Federico Gatto ◽  
Manuela Albertelli ◽  
Natale Musso

Salt intake is too high for safety nowadays. The main active ion in salt is sodium. The vast majority of scientific evidence points out the importance of sodium restriction for decreasing cardiovascular risk. International Guidelines recommend a large reduction in sodium consumption to help reduce blood pressure, organ damage, and cardiovascular risk. Regulatory authorities across the globe suggest a general restriction of sodium intake to prevent cardiovascular diseases. In spite of this seemingly unanimous consensus, some researchers claim to have evidence of the unhealthy effects of a reduction of sodium intake, and have data to support their claims. Evidence is against dissenting scientists, because prospective, observational, and basic research studies indicate that sodium is the real villain: actual sodium consumption around the globe is far higher than the safe range. Sodium intake is directly related to increased blood pressure, and independently to the enlargement of cardiac mass, with a possible independent role in inducing left ventricular hypertrophy. This may represent the basis of myocardial ischemia, congestive heart failure, and cardiac mortality. Although debated, a high sodium intake may induce initial renal damage and progression in both hypertensive and normotensive subjects. Conversely, there is general agreement about the adverse role of sodium in cerebrovascular disease. These factors point to the possible main role of sodium intake in target organ damage and cardiovascular events including mortality. This review will endeavor to outline the existing evidence.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jennifer A. Smith ◽  
Jeremy Raisky ◽  
Scott M. Ratliff ◽  
Jiaxuan Liu ◽  
Sharon L. R. Kardia ◽  
...  

Abstract Background Epigenetic age acceleration, a measure of biological aging based on DNA methylation, is associated with cardiovascular mortality. However, little is known about its relationship with hypertensive target organ damage to the heart, kidneys, brain, and peripheral arteries. Methods We investigated associations between intrinsic (IEAA) or extrinsic (EEAA) epigenetic age acceleration, blood pressure, and six types of organ damage in a primarily hypertensive cohort of 1390 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. DNA methylation from peripheral blood leukocytes was collected at baseline (1996–2000), and measures of target organ damage were assessed in a follow-up visit (2000–2004). Linear regression with generalized estimating equations was used to test for associations between epigenetic age acceleration and target organ damage, as well as effect modification of epigenetic age by blood pressure or sex. Sequential Oligogenic Linkage Analysis Routines (SOLAR) was used to test for evidence of shared genetic and/or environmental effects between epigenetic age acceleration and organ damage pairs that were significantly associated. Results After adjustment for sex, chronological age, and time between methylation and organ damage measures, higher IEAA was associated with higher urine albumin to creatinine ratio (UACR, p = 0.004), relative wall thickness (RWT, p = 0.022), and left ventricular mass index (LVMI, p = 0.007), and with lower ankle-brachial index (ABI, p = 0.014). EEAA was associated with higher LVMI (p = 0.005). Target organ damage associations for all but IEAA with LVMI remained significant after further adjustment for blood pressure and antihypertensive use (p < 0.05). Further adjustment for diabetes attenuated the IEAA associations with UACR and RWT, and adjustment for smoking attenuated the IEAA association with ABI. No effect modification by age or sex was observed. Conclusions Measures of epigenetic age acceleration may help to better characterize the functional mechanisms underlying organ damage from cellular aging and/or hypertension. These measures may act as subclinical biomarkers for damage to the kidney, heart, and peripheral vasculature; however more research is needed to determine whether these relationships remain independent of lifestyle factors and comorbidities.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Minjung Kho ◽  
Wei Zhao ◽  
Scott M. Ratliff ◽  
Farah Ammous ◽  
Thomas H. Mosley ◽  
...  

Abstract Background Hypertension is a major modifiable risk factor for arteriosclerosis that can lead to target organ damage (TOD) of heart, kidneys, and peripheral arteries. A recent epigenome-wide association study for blood pressure (BP) identified 13 CpG sites, but it is not known whether DNA methylation at these sites is also associated with TOD. Methods In 1218 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, a cohort of hypertensive sibships, we evaluated the associations between methylation at these 13 CpG sites measured in peripheral blood leukocytes and five TOD traits assessed approximately 5 years later. Results Ten significant associations were found after adjustment for age, sex, blood cell counts, time difference between CpG and TOD measurement, and 10 genetic principal components (FDR q < 0.1): two with estimated glomerular filtration rate (eGFR, cg06690548, cg10601624), six with urinary albumin-to-creatinine ratio (UACR, cg16246545, cg14476101, cg19693031, cg06690548, cg00574958, cg22304262), and two with left ventricular mass indexed to height (LVMI, cg19693031, cg00574958). All associations with eGFR and four associations with UACR remained significant after further adjustment for body mass index (BMI), smoking status, and diabetes. We also found significant interactions between cg06690548 and BMI on UACR, and between 3 CpG sites (cg19693031, cg14476101, and cg06690548) and diabetes on UACR (FDR q < 0.1). Mediation analysis showed that 4.7% to 38.1% of the relationship between two CpG sites (cg19693031 and cg00574958) and two TOD measures (UACR and LVMI) was mediated by blood pressure (Bonferroni-corrected P < 0.05). Mendelian randomization analysis suggests that methylation at two sites (cg16246545 and cg14476101) in PHGDH may causally influence UACR. Conclusions In conclusion, we found compelling evidence for associations between arteriosclerotic traits of kidney and heart and previously identified blood pressure-associated DNA methylation sites. This study may lend insight into the role of DNA methylation in pathological mechanisms underlying target organ damage from hypertension.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Terentes-Printzios ◽  
C Vlachopoulos ◽  
L Korogiannis ◽  
G Christopoulou ◽  
P Xydis ◽  
...  

Abstract Background/Introduction Cardiac autonomic dysfunction and target organ damage are associated with increased cardiovascular mortality and arrhythmias. Purpose The aim of the study was to investigate the effect of heart rate variability (HRV) and markers of target organ damage in the prognosis of future arrhythmic events. Methods We studied 292 untreated at baseline hypertensives (mean age 53±13, 153 males). Cardiac autonomic function was evaluated by analysis of short-term HRV measures over 24-h using 24-h ambulatory blood pressure monitoring and the standard deviation of the measurements. Echocardiography was also performed and left ventricular mass index (LVMI) was estimated with the Demereux formula. Aortic stiffness was assessed with carotid-femoral pulse wave velocity (cfPWV) and wave reflections with aortic augmentation index corrected for heart rate (Alx@75). Patients were followed up for a median period of 13 years. The primary endpoint was a composite of atrial/ventricular tachycardias, symptomatic multiple premature ventricular contractions, second and third-degree heart blocks and pacemaker/defibrillator placement. Results In comparison without events, patients with the primary endpoint (n=37, 13%) had lower 24-h daytime HRV (9.6 beats per minute vs. 11.1 beats per minute, p=0.005), higher systolic blood pressure (168 mmHg vs. 163 mmHg, p=0.003), higher cfPWV (8.4 m/s vs. 7.7 m/s, p=0.005), higher LVMI (133 g/m2 vs. 122 g/m2, p=0.002) and higher AIx@75 (29.0% vs. 26.3%, p=0.043). In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of HRV, cfPWV, LVMI and AIx@75 to discriminate subjects with arrhythmic events. The area under the curve (AUC) and 95% CIs of the ROC curves were AUC=0.35 (95% CI: 0.26–0.44, p=0.003) for HRV, AUC=0.64 (95% CI: 0.54–0.73, P<0.006) for cfPWV, AUC=0.67 (95% CI: 0.58–0.75, P=0.001) for LVMI and AUC=0.55 (95% CI: 0.47–0.64, P=0.298) for AIx@75 (Figure). In Cox regression analysis, only HRV was associated with increased risk of arrhythmic events (Hazard ratio per 1 unit =0.87, 95% Confidence intervals 0.76 to 0.995, p=0.043) when adjusted for age, gender, cfPWV, LVMI and AIx@75. ROC curves of HRV & target organ damage Conclusions Low heart rate variability is associated with increased risk of future arrhythmic events suggesting an early sympathovagal imbalance that could lead to future events in hypertension.


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