Renal biomarkers reflect overall hypertensive organ damage: “one organ to rule them all”

Abstract Background/Introduction Hypertension is associated with higher cardiovascular risk as well as several markers of subclinical target organ damage (TOD). Albumin to creatinine ratio (ACR) in urine has been recognized as an independent risk factor for cardiovascular events. Purpose We hypothesized that there is a relationship between ACR and markers of TOD in never-treated hypertensives. Methods We enrolled 924 consecutive essential hypertensives (mean age 53±12 years, 486 males) without known cardiovascular disease (CVD). Markers of subclinical TOD [left ventricular mass index (LVMI), pulse wave velocity (PWV), ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR)] were evaluated in all patients. LVMI was assessed echocardiographically using the Devereux formula. Carotid-femoral PWV was estimated with the Complior device. eGFR was calculated by the Cockcroft-Gault formula. ABI was calculated by dividing the highest ankle systolic blood pressure by the highest brachial systolic blood pressure. Results ACR exhibited significant association with LVMI (r=0.277, p<0.001, Figure), PWV (r=0.277, p<0.001) ABI (r=−0.078, p=0.018) and eGFR (r=−0.100, p=0.002). In further analysis, ACR was associated with TOD as suggested by the 2018 European Guidelines for Hypertension [left ventricular hypertrophy (LVMI>115 g/m2 in men and >95 g/m2 in women), increased PWV (PWV>10m/s), decreased ABI (ABI<0.9) and decreased renal function (eGFR<60ml/min)]. Specifically, ACR exhibited significant association with the number of TOD and this association was independent of age and gender (p<0.05). Conclusions Our findings support the close relationship between ACR and TOD in hypertension, as well as, the predictive ability of ACR for TOD. FUNDunding Acknowledgement Type of funding sources: None. Association between LVMI and ACR

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Prevalence, Biochemical and Clinical Characteristics of Resistant Hypertension

Revista de Chimie ◽

10.37358/rc.18.10.6637 ◽

2018 ◽

Vol 69 (10) ◽

pp. 2845-2849

Author(s):

Daniela Gurgus ◽

Elena Ardeleanu ◽

Carmen Gadau ◽

Roxana Folescu ◽

Ioan Tilea ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Resistant Hypertension ◽

Clinical Characteristics ◽

Salt Intake ◽

Target Organ Damage ◽

Multivariate Logistic Regression Analysis ◽

Organ Damage ◽

Left Ventricular ◽

High Salt Intake

The objectives of the present study were to evaluate the prevalence of resistant hypertension (RH) in primary care setting and to analyse its biochemical and clinical characteristics. After 3 months of treatment and evaluation, 721 (14.01%) of 5,146 patients with hypertension did not reach target office blood pressure of [ 140/90 mmHg. After exclusion of �white-coat effect� with ambulatory blood pressure, of secondary and pseudo- resistant hypertension, prevalence of RH was 6.74%. Lifestyle factors associated with RH were physical inactivity, obesity, high salt intake, smoking and excessive alcohol ingestion. Compared to controlled hypertension, RH patients presented higher incidence of family history of cardiovascular disease (38.90% vs 25.94%), diabetes mellitus (34.87% vs 19.01%), impaired fasting glucose (21.91% vs 19.07%), target organ damage (29.1% vs 15.95%), and cardiovascular disease (27.09% vs 17.06%). Dyslipidaemia (52.90% vs 42.03%), fasting plasma glucose (116.10�38.9 vs 107.80�37.2), HbA1c (6.41�1.42 vs 5.96�0.94), serum creatinine (1.09�0.27 vs 1.03�0.24) and microalbuminuria (21.90% vs 10.95%) were significantly higher in RH. Predictors of RH, determined by a multivariate logistic regression analysis were left ventricular hypertrophy (OD 2.14, 95% CI 1.32-3.69), renal impairment expressed as eGFR [ 60 ml/min/1.73m2 (OD 1.62, 95% CI 1.21-2.21) and the presence of cardiovascular disease (OD 1.48, 95% CI 1.02-2.16).

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220 Relationship of blood pressure variability to left ventricular mass and micro-albuminuria as measures of target-organ damage

Journal of Hypertension ◽

10.1097/00004872-199312050-00389 ◽

1993 ◽

Vol 11 (5) ◽

pp. S494

Author(s):

Dirk P. Veerman ◽

K. de Blok ◽

B. L.M. Delemarre ◽

Gert A. van Montfrans

Keyword(s):

Blood Pressure ◽

Left Ventricular Mass ◽

Blood Pressure Variability ◽

Target Organ Damage ◽

Organ Damage ◽

Left Ventricular ◽

Target Organ ◽

Ventricular Mass ◽

Relationship Of

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

Hypertension ◽

10.1161/hyp.60.suppl_1.a432 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

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.

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Feline blood pressure measurement: when is it needed?

Companion Animal ◽

10.12968/coan.2021.0063 ◽

2021 ◽

Vol 26 (11) ◽

pp. 222-228

Author(s):

Sarah Caney

Keyword(s):

Blood Pressure ◽

Systolic Blood Pressure ◽

Pressure Measurement ◽

Blood Pressure Measurement ◽

Target Organ Damage ◽

Organ Damage ◽

Target Organ ◽

Systemic Hypertension ◽

Ophthalmological Examination ◽

Target Organs

Systemic hypertension is a common disorder, primarily affecting older cats. Most cases are secondary to underlying medical conditions, such as chronic kidney disease. If left untreated, systemic hypertension has the potential to cause serious damage to certain target organs and can be fatal. Target organs include the nervous system, cardiovascular system, eyes and kidneys. Target organ damage to the eyes is often pathognomonic and is detected on ophthalmological examination in up to 80% of cats with systemic hypertension. Blood pressure measurement is essential in confirming a diagnosis and should be prioritised in cats showing evidence of target organ damage. Blood pressure screening of apparently healthy older cats is justified, since the risk of hypertension increases with age. Systemic hypertension is diagnosed in cats with persistent elevation in their systolic blood pressure of 160 mmHg or higher. Stress and anxiety can cause a transient increase in systolic blood pressure so measurements should be collected in a manner that is as calm and ‘cat friendly’ as possible. In the presence of confirmed target organ damage, a single high systolic blood pressure reading confirms systemic hypertension. Where no target organ damage is detectable, evidence of elevated systolic blood pressure on two or more occasions is needed to confirm the diagnosis.

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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17082811 ◽

2020 ◽

Vol 17 (8) ◽

pp. 2811 ◽

Cited By ~ 2

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.

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

BMC Medical Genomics ◽

10.1186/s12920-019-0585-5 ◽

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.

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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

BMC Medical Genomics ◽

10.1186/s12920-020-00791-0 ◽

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.

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

European Heart Journal ◽

10.1093/eurheartj/ehz745.0674 ◽

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.

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The Epidemiology of Plasma Renin

Clinical Science ◽

10.1042/cs0640273 ◽

1983 ◽

Vol 64 (3) ◽

pp. 273-280 ◽

Cited By ~ 78

Author(s):

T. W. Meade ◽

J. D. Imeson ◽

D. Gordon ◽

W. S. Peart

Keyword(s):

Blood Pressure ◽

Systolic Blood Pressure ◽

Target Organ Damage ◽

Plasma Renin ◽

Organ Damage ◽

Blood Cholesterol ◽

Occupational Groups ◽

Predisposing Factor ◽

Significant Difference ◽

Epidemiological Characteristics

1. The epidemiological characteristics of plasma renin activity (PRA) were established in 1999 members of occupational groups in North and West London. 2. The main finding was that PRA was inversely associated with systolic blood pressure in men, the percentage fall in PRA (on a log scale) being 8.4% for each increase of one standard deviation in systolic blood pressure. There was a less obvious inverse relationship in women. 3. However, blood pressure accounted for less than 1% of the variance in PRA. 4. Mean PRA in both smokers and ex-smokers was about 20% higher than in non-smokers. 5. PRA fell with increasing age, was lower in women than in men and considerably lower in blacks (of either sex) than whites. 6. PRA was lower in the first quarter of the menstrual cycle than in the rest of the cycle. 7. Haemoglobin, blood cholesterol, leucocyte count and Factor VIII were positively correlated with PRA. 8. PRA was lower in men with diagnosed hypertension than in those without; there was no significant difference in the women. 9. PRA was lower in those who had had myocardial infarcts in the past than in those who had not. 10. The data as a whole suggest that it may be low, not high, levels of PRA which are associated with increased risks of cardiovascular disease in which hypertension is a predisposing factor. 11. The explanation may be a homoeostatic fall in PRA in response to a rise in blood pressure rather than a major causal role for PRA in the pathogenesis of essential hypertension and target-organ damage.

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