scholarly journals Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older African Americans

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jennifer A. Smith ◽  
Jeremy Raisky ◽  
Scott M. Ratliff ◽  
Jiaxuan Liu ◽  
Sharon L. R. Kardia ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dna Methylation ◽  
African Americans ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Effect Modification ◽  
Target Organ ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration

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.

scholarly journals Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Minjung Kho ◽  
Wei Zhao ◽  
Scott M. Ratliff ◽  
Farah Ammous ◽  
Thomas H. Mosley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dna Methylation ◽  
African Americans ◽  
Genetic Epidemiology ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Cpg Sites ◽  
Cell Counts

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.

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
Keyword(s):  
Blood Pressure ◽  
Left Ventricular Mass ◽  
Target Organ Damage ◽  
Albumin Excretion Rate ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Related Target ◽  
Ventricular Mass ◽  
Lv Mass

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.

scholarly journals Sodium Intake and Target Organ Damage in Hypertension—An Update about the Role of a Real Villain

2020 ◽  
Vol 17 (8) ◽  
pp. 2811 ◽  
Author(s):  
Federica Nista ◽  
Federico Gatto ◽  
Manuela Albertelli ◽  
Natale Musso
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Sodium Intake ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Main Role ◽  
Sodium Consumption

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.

P3833Low heart rate variability is associated with future arrhythmic events in hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Terentes-Printzios ◽  
C Vlachopoulos ◽  
L Korogiannis ◽  
G Christopoulou ◽  
P Xydis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Primary Endpoint ◽  
Target Organ Damage ◽  
Roc Curves ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Increased Risk

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.

scholarly journals The patients of high cardiovascular risk of healthy: unrecognized metabolic syndrome

2016 ◽  
Vol 13 (4) ◽  
pp. 60-65
Author(s):  
N V Blinova ◽  
Yu V Zhernakova ◽  
I E Chazova ◽  
E V Oshchepkova
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Blood Pressure Monitoring ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Control Group ◽  
Vasoactive Mediators ◽  
Atherosclerotic Process

Aims: to study the target organ damage in patients with metabolic syndrome (MS) and arterial hypertension (AH) 1 degree. Design and methods. We included 20 healthy volunteers and 60 patients with MS, AH 1 degree and dyslipidemia. Office blood pressure, 24-hour ambulatory blood pressure monitoring, measurements of the endothelial vasoactive mediators, carotid ultrasonography and echocardiography had performed at baseline. Results. The majority of patients with MS and AH 1 degree had metabolic abnormalities; the levels of vasoactive mediators were higher in comparison with control group; 30% of patients had signs of atherosclerotic process in carotid arteries; 40% of patients had left ventricular hypertrophy. Conclusion: the results showed high prevalence of target organ damage in patients with MS and AH 1 degree.

scholarly journals Associations between measurements of central blood pressure and target organ damage in high-risk patients

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Ki-Hyun Jeon ◽  
Hack-Lyoung Kim ◽  
Woo-Hyun Lim ◽  
Jae-Bin Seo ◽  
Sang-Hyun Kim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Risk ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Central Blood Pressure ◽  
Atherosclerotic Cardiovascular Disease ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background It is not well-known which components of central blood pressure (CBP) are more influential to target organ damage (TOD). This study aimed to determine the relationship between CBP measurements and various types of TOD in high-risk patients. Methods A total of 148 patients who had documented atherosclerotic cardiovascular disease or its multiple risk factors were prospectively enrolled. CBP was measured by using applanation tonometry of the radial artery. The following nine TOD parameters were evaluated: left ventricular mass index, relative wall thickness, septal e′ velocity, septal E/e′, brachial-ankle pulse wave velocity, ankle-brachial index, estimated glomerular filtration rate, urine protein and obstructive coronary artery disease. Results The mean age of the study population was 67.1 ± 9.0 years and 108 (73 %) were male. Among four CBP measurements (systolic, diastolic, mean, and pulse pressures), central pulse pressure (CPP) was associated with the largest number of TOD parameters. As CPP increased, the number of TOD increased (P = 0.010), but this association was not observed in other CBP measurements (P > 0.05 for each). Conclusions CPP had a stronger correlation with TOD than other CBP measurements. Non-invasive CPP could be a useful indicator for predicting TOD in patients at high coronary risk.

P804The significance of 24h blood pressure variability improvement regarding target organ damage indices three years after medical treatment initiation in essential hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Triantafyllidi ◽  
A Schoinas ◽  
D Benas ◽  
D Birba ◽  
D Voutsinos ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Medical Treatment ◽  
Blood Pressure Variability ◽  
Treatment Initiation ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Hypertensive Patients ◽  
Damage Indices

Abstract Background Blood pressure variability (BPV) has been associated with development, progression and severity of cardiac and vascular organ damage and with an increased risk of cardiovascular events and mortality, independently adding to cardiovascular risk, over and above the contribution of elevated mean BP levels. We aimed to explore any correlation between differences in BPV and target organ damage indices (TOD) in hypertensive patients three years after medical treatment initiation. Methods At baseline and before medical treatment initiation, we measured 24h average SBP and DBP as well as 24h systolic BPV after 24h ambulatory blood pressure monitoring (ABPM) in newly diagnosed and never treated hypertensive patients (n=171, mean age=52+12 years, 110 males, 24h average SBP/DBP=138+10/87+9 mmHg, 24h systolic BPV=15+3) who were also subjected to arterial stiffness by carotid-femoral pulse wave velocity (PWV), left ventricular hypertrophy by left ventricular mass index (LVMI) and coronary flow reserve (CFR) estimations. All the above tests were repeated approximately three years later after treatment initiation. Results Patients were characterized as controlled (n=113, mean age=54+12 years, 62 males, 24h average SBP/DBP=118+6/71+6 mmHg) or non-controlled hyperensives (n=58, mean age=48+11 years, 48 males, 24h average SBP/DBP=133+8/83+7 mmHg) based on ABPM results three years later (controlled BP=24h average BP<130/80 mmHg). In the whole population, 24h average SBP/DBP, systolic BPV (p<0.001) and LVMI (p=0.01) were decreased while systolic BPV difference was related with LVMI difference (r=0.27, p<0.001). In controlled hypertensives, 24h average SBP/DBP, systolic BPV (p<0.001) and LVMI (p=0.02) were decreased while systolic BPV difference was related with LVMI difference (r=0.35, p<0.001). In non-controlled hypertensives, 24h average SBP (p=0.001), DBP p<0.001) and systolic BPV (p=0.04) were decreased while PWV was increased (p=0.03) and no correlations were found between systolic BPV and TOD. Correlation between BPV and LVMI Conclusions It seems that antihypertensive-induced systolic BPV improvement relate with cardiovascular risk decrease occur only in the setting of blood pressure treated within normal limits and confirmed by ABPM. Our study confirms that left ventricular mass between other TOD primarily improves due to successful antihypertensive treatment.

scholarly journals The relationship of plasma renin , angiotensin , and aldosterone levels to blood pressure variability and target organ damage in children with essential hypertension

2020 ◽  
Author(s):  
Yang Liu ◽  
Yao Lin ◽  
Ming-Ming Zhang ◽  
Tong Zheng ◽  
Xiao-Hui Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Essential Hypertension ◽  
Blood Pressure Variability ◽  
Target Organ Damage ◽  
Plasma Renin ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Renin Angiotensin

Abstract Background To investigate the relationships of plasma renin, angiotensin, and aldosterone levels to blood pressure variability and target organ damage in children with essential hypertension. Methods A case-control study was conducted on 132 children diagnosed with essential hypertension(103 males and 29 females with the mean age of 11.8 ± 2.4 years). The plasma RAAS levels were measured using the enhanced chemiluminescence method, the ambulatory blood pressure was monitored for 24 h, and then the average real variability (ARV) was calculated. Data on indicators were used for assessing cardiac and renal damages. The correlations of plasma renin, angiotensin, and aldosterone (RAAS) levels to blood pressure variability (BPV) and target organ damage (TOD) were studied. A comparison between the groups was conducted using SPSS 20． Results Among the 132 children, 55 cases had target organ damage. The 24-h ARV and the daytime ARV of the systolic blood pressure of the high angiotensin II (AT II) group was significantly higher than that of the normal AT II group (t = 2.175, P = 0.031; t = 2.672, P = 0.009). Plasma AT II and aldosterone levels were significantly associated with the left ventricular mass index (r = 0.329, P= 0.0001; r = 0.175, P = 0.045). Linear regression analysis showed that AT II [ β± s.e.= 0.025±0.006, 95% CI ( 0.013–0.038), P = 0.0001] and aldosterone [ β± s.e.= 0.021±0.007, 95% CI( 0.008–0.034), P = 0.002] were risk factors for LVH. Conclusions The AT II level in children with essential hypertension affected the variability of the 24-h and the daytime SBP. Plasma AT II and aldosterone levels were associated with cardiac damage. Results from this study indicated that AT II and aldosterone are risk factors for LVH in childhood hypertension and are of great significance for improving the clinical prognosis of pediatric patients with hypertension.

scholarly journals Ambulatory blood pressure is better associated with target organ damage than clinic blood pressure in patients with primary glomerular disease

2020 ◽  
Author(s):  
ruowei wen ◽  
xiaoqiu chen ◽  
ye zhu ◽  
jianting ke ◽  
yi du ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ambulatory Blood Pressure ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Glomerular Disease ◽  
Target Organ ◽  
Clinic Blood Pressure ◽  
Multivariate Logistic Regression ◽  
Primary Glomerular Disease

Abstract Background: Blood pressure is an important and modifiable cardiovascular risk factor. Ambulatory blood pressure monitoring (ABPM) provides valuable prognostic information in patients with chronic kidney disease (CKD), yet little is known about the association of various types of BP measurements with target organ damage (TOD) in patients with primary glomerular disease. The goal of this study was to investigate whether ambulatory blood pressure is better associated with TOD than clinic blood pressure in patients with primary glomerular disease. Methods: 1178 patients with primary glomerular disease were recruited in this cross-sectional study. TOD were assessed by the following 4 parameters: left ventricular mass index (LVMI or LVH, left ventricular hypertrophy), estimated glomerular filtration rate (eGFR<60ml/min/1.73m 2 ), albumin-to-creatinine ratio (ACR≥30mg/g) and carotid intima-media thickness (cIMT) or plaque. Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were used to evaluate the relationship between ambulatory or clinic systolic blood pressure (SBP) indexes and TOD. Results: Among 1178 patients (mean age, 39 years,54% men), 116, 458, 1031 and 251 patients had LVH, eGFR < 60 ml/min/1.73m 2 , ACR≥30mg/g and cIMT≥0.9mm or plaque respectively. Area under ROC curves for TOD in ambulatory SBP, especially nighttime SBP, was greater than that in clinic SBP ( P <0.05). Multivariate logistic regression analyses showed that 24h SBP, daytime SBP and nighttime SBP were significantly associated with LVH, eGFR<60 ml/min/1.73m 2 and ACR≥30mg/g after adjustment for clinic SBP, while the association of clinic SBP was attenuated after further adjustment for nighttime SBP. Conclusions: Ambulatory blood pressure, especially nighttime blood pressure, is superior to clinic blood pressure in estimating TOD in patients with primary glomerular disease. Key Words: Ambulatory blood pressure, Clinic blood pressure, Target organ damage, Primary glomerular disease

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