Subclinical Target Organ Damage Research Articles

Silent brain infarcts, peripheral vascular disease and the risk of cardiovascular events in patients with hypertension.

We aimed to study the relationship between cerebral small vessel disease (cSVD) lesions, as markers of subclinical target organ damage (TOD) in the brain, and incident cardiovascular events (CVE). Data from the ISSYS (Investigating Silent Strokes in hYpertensives Study), which is a longitudinal and observational study conducted in patients with hypertension aged 50-70 years, and stroke-free at the inclusion. At the baseline visit, participants underwent a clinical interview, a brain MRI, urine and blood sampling collection and vascular testing studies. Therefore, we obtained markers of TOD from the brain [white matter hyperintensities, silent brain infarcts (SBI), cerebral microbleeds and enlarged perivascular spaces (EPVS)], from kidney (microalbuminuria, glomerular filtration) and regarding large vessels [ankle-to-brachial index (ABI), carotid-femoral pulse wave velocity]. Survival analyses were used to assess the relationship between these predictors and the incidence of cardiovascular events (CVE). We followed-up 964 individuals within a median time of 5 years (4.7-5), representing 4377.1 persons-year. We found 73 patients presenting incident CVE, which corresponds to a rate of 8.2%. We found ABI less than 0.9 [hazard ratio, 2.2; 95% confidence interval (CI) 1.17-4.13, P value = 0.014] and SBI (hazard ratio, 2.9; 95% CI 1.47-5.58, P value = 0.002) independently associated with higher risk of incident CVE. The inclusion of both variables in a clinical model resulted in an increased discrimination of individuals with new CVE of 4.72%, according to the integrated discrimination index. Assessment of SBI and ABI less than 0.9 may refine the cardiovascular risk stratification in patients with hypertension.

Subclinical target organ damage as risk stratification parameter in hypertensive patients.

Subclinical target organ damage as risk stratification parameter in hypertensive patients.

Isolated diastolic hypertension in childhood and risk of adult subclinical target organ damage: a 30-year prospective cohort study.

Background:Data on the association of isolated diastolic hypertension (IDH) in childhood with adult cardiovascular risk are scarce. This study aimed to estimate the prevalence of IDH in adolescents and to explore the impact of IDH in childhood on adult subclinical target organ damage (STOD).Methods:This longitudinal study consisted of 1738 school children (55.4% boys) aged 6–15 years from rural areas of Hanzhong, Shaanxi, who were followed for 30 years. Their blood pressure was recorded to define the hypertension subtypes: normotension, IDH, isolated systolic hypertension (ISH) and mixed hypertension. Tracked STOD included arterial stiffness (n = 1738), albuminuria (n = 1652) and left ventricular hypertrophy (LVH) (n = 1429).Results:Overall, the prevalence of IDH, ISH and mixed hypertension was 5.4, 2.2 and 3%, respectively, and there was no gender difference. Over 30 years, 366 (21.1%) of participants developed arterial stiffness, 170 (10.3%) developed albuminuria and 68 (4.8%) developed LVH. Compared with normotensive participants, IDH in childhood had higher risk ratio (RR) of experiencing arterial stiffness (RR, 1.66; 95% CI, 1.01–2.76) and albuminuria (RR, 2.27; 95% CI, 1.35–4.16) in adults after being fully adjusted but not LVH. However, if the elevated blood pressure in children was used as the reference standard, IDH in childhood was associated with adult LVH (RR, 2.48; 95% CI, 1.28–4.84).Conclusion:IDH accounts for a higher proportion of adolescent hypertension subtypes and can increase the risk of adult STOD. These results highlight the necessity of improving the prevention, detection and treatment of IDH in adolescents.

CARDIOVASCULAR RISK AND SUBCLINICAL TARGET ORGAN DAMAGE IN A YOUNG ADULT POPULATION PROVIDED BY A PRIMARY HEALTHCARE UNIT

Objective: To evaluate cardiovascular (CV) risk factors and subclinical target organ damage in a young and apparently healthy population assisted in a Primary Healthcare unit Design and method: A cross-sectional population study for CV risk assessment in adults aged 20–50 years old provided by a Primary Healthcare Unit. A total of 632 individuals were evaluated (40% male; mean age 36 ± 9 years). Sociodemographic, anthropometric data, and traditional CV risk factors were recorded. All underwent office Blood Pressure (BP) and pulse pressure (PP) (systolic BP minus diastolic BP) was calculated. Ankle-brachial index (ABI) was also calculated after BP measurements in the 4 limbs. The median of the ABI was 1.14 [1.08–1.22], which is the cutoff point used to define early changes. All participants were submitted to ECG to calculate Sokolow-Lyon Index (SLI) and Cornell Voltage Index (CVI) for left ventricular hypertrophy diagnosis. We considered the median of the SLI (20 mm) and the CVI (11 mm) as the cutoff point for early alterations. Results: The prevalence of hypertension was 16%. The median [IQR] office PP was 46 [39–52] mmHg. Elevated Office PP (> 60 mmHg) were identified in 64 participants. High office PP was more frequent in men, obese, with increased neck circumference and lower ABI (1.07 vs 1.16, p < 0.001). It was also associated with higher voltage index: SLI 21.9 vs 19.8, p = 0.04 and CVI 13.4 vs 7.1, p = 0.03. Individuals with decreased ABI are more obese with smaller neck circumference (10 vs 5%, p = 0.03). They also had higher systolic BP (125 vs 119 mmHg, p < 0.001) and PP (49 vs 43 mmHg, p < 0.001). A total of 362 ECGs were performed. Increased SLI was more frequent in men, younger and overweight, in addition to a higher prevalence of hypertension and higher PP. Those with increased CVI are more often male, obese with higher BP levels. Conclusions: In this young population, early changes in subclinical target organ damage already identify a higher CV risk profile, indicating the importance of implementing primary prevention measures to reduce this risk.

ASSOCIATION OF CEREBRAL OXYGENATION DURING EXERCISE WITH TARGET ORGAN DAMAGE IN HYPERTENSIVE AND NORMOTENSIVE INDIVIDUALS

Objective: To investigate whether indices of cerebral oxygenation during exercise correlate with subclinical markers of target organ damage (TOD), namely carotid intima-media thickness (cIMT), arterial stiffness, and retinal vessel diameter in newly diagnosed hypertensives and healthy individuals. Design and method: Hypertension was diagnosed using 24-hour ambulatory blood pressure (BP) monitoring. Patients with white coat or masked hypertension were excluded. Cerebral oxygenation was measured continuously during a three-minute isometric hand grip exercise at 30% of maximal voluntary contraction using near infrared spectroscopy. The average response during exercise in oxygenated-hemoglobin (O2Hb), deoxygenated-hemoglobin (HHb), and total-hemoglobin (tHb, reflecting changes in regional blood volume) were examined. CIMT was measured using ultrasound, arterial stiffness was estimated with augmentation index and pulse wave velocity, and retinal vessel diameters were estimated by the central retinal arteriolar (CRAE) and vein (CRVE) equivalent and retinal arteriovenous ratio (AVR). Univariate analyses were performed and partial correlation was used to account for traditional cardiovascular risk factors to identify independent associations between cerebral oxygenation indices and TOD. Results: Fifty-two newly-diagnosed, never treated hypertensives and 41 healthy normotensive individuals with no known medical history of any other disease were included in our study. There were no differences in anthropometric and laboratory variables between groups except for their BP levels, as expected by study design. Mean cIMT was negatively correlated with the average exercise response in cerebral oxygenation (rhoO2Hb = -0.348, pO2Hb = 0.001; rhotHb = -0.253, ptHb = 0.02). Augmentation index was negatively correlated with cerebral-oxygenation during exercise (rhoO2Hb = -0.374, p < 0.001; rhotHb = -0.332, p = 0.02), whereas no significant correlation was observed between pulse wave velocity and cerebral oxygenation indices. In the adjusted analysis, cerebral oxygenation was correlated with central retinal arteriolar diameter (CRAE rO2Hb = 0.233, pO2Hb = 0.043). Conclusions: Our novel findings suggest that indices of cerebral oxygenation during a submaximal physical task are associated with markers of early, subclinical target organ damage, namely increased carotid intima-media thickness, arterial stiffness and retinal arteriolar narrowing in a population of newly diagnosed hypertensive individuals.

PREVALENCE OF TARGET ORGAN DAMAGE AND CARDIOVASCULAR RISK FACTORS IN PATIENTS OF THE IBERICAN STUDY

Objective: The general aim of IBERICAN study is to know the prevalence and incidence of cardiovascular risk factors and cardiovascular and renal disease in Spain. The aim of this abstract is to know the prevalence of subclinical target organ damage (TOD) and cardiovascular risk in population of the IBERICAN Study. Design and method: The IBERICAN Study is a longitudinal, observational, and multicentric study with subjects between 18 to 85 years of age, recruited in Primary Care (PC) and who will be follow up at least 10 years. The final sample size is estimated in 8,066 patients. We show the baseline characteristics of the patients in the first visit (n = 8,066). To define the TOD, we consider the ESH 2013 Guide criteria: pressure pulse in aged > 60 mmHg, ankle/brachial index < 0.9, microalbuminuria: albumin/creatinine ratio (between 30 - 299 mg/g), glomerular filtration (CDK-EPI < 60 ml/min), left ventricular hypertrophy (electrocardiogram or ECHO). Results: 2,052 patients presented TOD (25.4%). The most frequent cardiovascular risk in patients with TOD are: hypertension in 73.7% vs 39.1% p< 0.001, dyslipidemia in 65.3% vs 45.1% p < 0.001, obesity in 43% vs 32, 5% p < 0.001, type 2 diabetes mellitus (T2DM) in 35.2% vs 15% p < 0.001, sedentary lifestyle 66.2% vs 27.8% p = 0.2 and smoking in 11.1% vs 19.9% p < 0.001. Of the patients with TOD and hypertension had good control 46.4% vs 66.6% p < 0.001, TOD and T2DM 74.4% vs 66.2% p = 0.8, TOD and dyslipidemia 22.2% vs 30 .2% p < 0.001. 57% (n = 1,170) of the patients with TOD met the criteria for Metabolic Syndrome and 23.3% (n = 477) met premorbid metabolic syndrome. Conclusions: All cardiovascular risk factors were more frequent in patients with TOD, except for smoking. The most frequent cardiovascular rissk was hypertension arterial and the worst controlled was dyslipidemia. TOD classifies patients as having high cardiovascular risk, so being able to detect it in patients with one or more cardiovascular risk factor is relevant for the optimal therapeutic approach in primary prevention.

PREVALENCE OF TARGET ORGAN DAMAGE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN IBERICAN STUDY

Objective: The general aim of IBERICAN study is to know the prevalence and incidence of cardiovascular risk factors and cardiovascular and renal disease in Spain. The aim of this abstract is to know the prevalence of subclinical target organ damage (TOD) and type 2 of Diabetes mellitus (T2DM) in population of the IBERICAN Study. Design and method: The IBERICAN Study is a longitudinal, observational, and multicentric study with subjects between 18 to 85 years of age, recruited in Primary Care (PC) and who will be follow up at least 10 years. The final sample size is estimated in 8,066 patients. We show the baseline characteristics of the patients in the first visit (n = 8,066). To define the TOD, we consider the ESH 2013 Guide criteria: pressure pulse in aged > 60 mmHg, ankle/brachial index < 0.9, microalbuminuria: albumin/creatinine ratio (between 30 - 299 mg/g), glomerular filtration (CDK-EPI < 60 ml/min), left ventricular hypertrophy (electrocardiogram or ECHO). Results: 1,434 patients had T2DM (20.1%), 56.4% men. 44.8% of patients with T2DM had TOD. Of the patients with TOD, the mean BMI was 31.7 ± 9.6 Kg/m2. By type of TOD: pulse pressure at > 60 mmHg: 29.2%; ankle/brachial index < 0.9: 3.0%; microalbuminuria: 17.0%; left ventricular hypertrophy: 7.0%. The prevalence of cardiovascular risk factors in patients with T2DM and TOD compared to non-TOD was: Hypertension 84.8% vs 68.4%, p< 0.001; dyslipidemia 78.2% vs 71.6%, p < 0.01; obesity 52.0% vs 49.7% p = 0.376; alcohol consumption 17.0% vs 15.2% p = 0.369; smoking 12.4% vs 14.7%, p = 0.202; sedentary lifestyle 38.5% vs 33.7%, p = 0.061. Conclusions: The prevalence of TOD in patients with T2DM in primary care is high, half of the patients. By type of TOD, elevated pulse pressure in the elderly and microalbuminuria were the most prevalent. Arterial hypertension and dyslipidemia were more prevalent in patients with TOD.

ARTERIAL STIFFNESS FROM MONITORING OF QKD INTERVALL PREDICTS OVERALL MORTALITY

Objective: Markers of subclinical target organ damage increase cardiovascular risk prediction beyond traditional risk factors. Arterial stiffness is one of these parameters, and QKD intervall a marker of arterial stiffness. We aimed to precise if arterial stiffness through QKD intervall measurement could predict overall mortality. Design and method: The patients included in this study belong to the Bordeaux cohort of hypertensive started in 1984. It includes patients with essential hypertension and no cardiovascular complications or pathology likely to affect the prognosis. All the patients benefited from an ambulatory measurement of blood pressure coupled with the measurement of QKD interval (Diasys 200RK then Diasys integra and from 2020 Diasys 3 plus, Novacor, France). QKD interval is the time between the QRS wave on the ECG and the detection of the last Korotkoff sound on deflation of the cuff. The stiffer the arteries, the shorter the QKD intervall. The value obtained is expressed as a percentage of a theoretical normal value based on the height predicted value of a population of normal young subjects. In 2021, we made a systematic search of all cause deaths for all the patients in the registry from national institut INSEE. Results: We included 913 patients whose main characteristics are summarized in table 1. The average follow up period for the population was 11.88 ± 7.5 years. Cardiovascular prediction calcultated by the score SCORE, 24 h SBP and QKDh as a continuous or discontinuous variable were significantly and independently linked to the occurrence of cardiovascular complications or all cause deaths in multivariate Cox model. Conclusions: Arterial stiffness evaluated by the ambulatory measurement of QKD interval has an independent prognostic value in the hypertensive and add significant predictive information to the risk SCORE.

Prevalence of target organ damage in hypertensive patients with coexisting obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with cardiovascular risk and higher mortality. Assessment of subclinical organ lesions is significant for prevention of clinically manifested complications which might result in death. The aim of the study was to assess the prevalence of subclinical target organ damage in hypertensive patients with OSA, and to establish whether these lesions are dependent on the intensity of sleep-disordered breathing. The study covered 67 patients with OSA diagnosed on the basis of polygraphy. Depending on the apnea/hypopnea index (AHI), the patients were divided into two groups: G1 (n=32; AHI=5-30) and G2 (n=35; AHI>30). The control group C consisted of 31 hypertensive subjects with OSA risk estimated as low based on the Berlin Questionnaire (BQ). Each patient had the following parameters measured: intima-media thickness (IMT), ankle-brachial index (ABI), left ventricular mass index (LVMI), and estimated glomerular filtration rate (eGFR). The patients with severe OSA had significantly higher LVMI compared to the control group (130.99±44.6 g/m2 versus 106.61±27.86 g/m2; p=0.0332). The G2 group had higher eGFR than C (104.7±17.96 ml/min/1.73m2, 88.85±17.68 ml/min/1.73m2; p=0.0058). Similar results of eGFR were observed between G1 and C (104.35±21.06 ml/min/1.73m2, 88.85±17.68 ml/min/1.73m2; p=0.0081). G1 and G2 did not differ significantly in terms of eGFR. The other measured parameters, such as IMT and ABI, did not differ significantly between OSA and controls. Patients with severe OSA demonstrate signs of left ventricular hypertrophy, while early atherosclerotic lesions (ABI and IMT) were not more intense than in the control group. High eGFR levels may indicate hyperfiltration, which does not correlate with OSA intensity level.

Association of Cerebral Oxygenation During Exercise With Target Organ Damage in Middle-Aged Hypertensive and Normotensive Individuals.

The brain is one of the main target organs affected by hypertension. Impaired cerebral oxygenation during exercise is an indicator of cerebral dysfunction. We aimed to investigate whether cerebral oxygenation during exercise correlates with subclinical markers of early target organ damage in a population of middle-aged, newly diagnosed hypertensive and healthy individuals. Carotid intima-media thickness (cIMT) was measured using ultrasound, arterial stiffness was estimated measuring the augmentation index and pulse wave velocity, and retinal vessel diameter was assessed via the central retinal-arteriolar and vein equivalent and retinal-arteriovenous ratio. Participants (n = 93) performed a 3-minute isometric handgrip exercise. Cerebral prefrontal oxygenation was measured continuously using near infrared spectroscopy. The average exercise responses in oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (tHb) were assessed. Univariate analyses were performed; partial correlation was used to account for traditional cardiovascular risk factors to identify independent associations between cerebral-oxygenation indices and early markers of target organ damage. Mean cIMT was negatively correlated with the average exercise response in cerebral oxygenation (rhoO2Hb = -0.348, PO2Hb = 0.001; rhotHb = -0.253, Pthb = 0.02). Augmentation index was negatively correlated with cerebral oxygenation during exercise (rhoO2Hb = -0.374, P < 0.001; rhotHb = -0.332, P = 0.02), whereas no significant correlation was observed between pulse wave velocity and cerebral-oxygenation indices. In the adjusted analysis, cerebral oxygenation was correlated with central retinal arteriolar diameter (CRAE r = 0.233, P = 0.043). Our novel findings suggest that indices of lower cerebral oxygenation during a submaximal physical task are associated with markers of early, subclinical target organ damage, namely increased cIMT, arterial stiffness, and arteriolar retinal narrowing in newly diagnosed, untreated, hypertensive individuals.

The relationship of endothelial function and arterial stiffness with subclinical target organ damage in essential hypertension.

This study aimed to explore whether brachial‐ankle pulse wave velocity (baPWV) and brachial artery flow‐mediated dilation (FMD) or the interaction of both parameters are associated with subclinical target organ damage (STOD) indices in patients with essential hypertension. A total of 4618 patients registered from January 2015 to October 2020 were included. baPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Whereas left ventricular hypertrophy (LVH), urine albumin‐creatinine ratio (UACR), and carotid intima‐media thickness (CIMT) were obtained as STOD indicators. On multivariable logistic regression analysis with potential confounders, higher quartiles of baPWV and FMD were significantly associated with an increased risk of STOD. In patients <65 years of age, the odds ratio (OR) of LVH, UACR, and CIMT ≥.9 mm for the fourth versus the first quartile of baPWV were 1.765 (1.390–2.240), 2.832 (2.014–3.813), and 3.075 (2.315–4.084), respectively. In interaction analysis, an increase in baPWV shows a progressively higher risk of STOD across the quartiles of FMD. Also, the estimated absolute risks of LVH, UACR, and CIMT ≥.9 mm for the first to fourth quartile of baPWV increased from 1.88 to 2.75, 2.35 to 4.44, and 3.10 to 6.10, respectively, in patients grouped by FMD quartiles. The addition of baPWV to FMD slightly improved risk prediction for STOD. BaPWV and FMD were independently associated with an increased risk of STOD in patients with essential hypertension especially among patients <65 years of age. Patients with elevated baPWV and decreased FMD parameters are at increased risk of STOD.

Abstract P033: Higher Ambulatory Sbp Is Associated With Increasing Number Of Target Organ Abnormalities In Youth: The Ship Ahoy Study

Hypertension is associated with elevated left ventricular mass index (LVMI), cardiac dysfunction and increased arterial stiffness in adults which predict cardiovascular (CV) events. The extent to which elevated BP in youth is associated with subclinical CV target organ damage (TOD) is not known. We explored the relation between BP level and number of TOD abnormalities (nTOD). We measured clinic and ambulatory BP (ABP), anthropometrics, and nTOD in 244 adolescents (mean 15.5 + 1.8 years, 67% white, 60% male). Subjects were recruited as low-risk (L=98, SBP%&lt;80 th %), mid-risk (Mid=60, SBP% 80-&lt;90 th %); and high-risk (H=86, SBP% &gt;=90 th %) based on mean of 6 aneroid clinic BPs by age-, sex- and height-specific cut-points. 24-hour ABP was measured with an oscillometric device per pediatric guidelines. Four measures of TOD were: LVMI &gt; 38.6 g/m 2.7 ; LV systolic strain (Strain %) &gt; -18; LV diastolic function (E/e’) &gt; 8; pulse wave velocity (PWV) &gt; 5.8 m/sec. ANOVA was used to evaluate differences in CV risk factors and chi square for differences in nTOD across groups. Logistic regression models were used to determine if clinic and/or ABP was an independent predictor of nTOD after adjustment for age, sex, race, and BMI z-score. BP groups did not differ in BMI z-score. Clinic and ABP systolic and diastolic BP increased across BP groups. The distribution of nTOD was shifted towards higher BP group with most nTOD= 0 (47%) in the L and all (100%) nTOD = 4 in the H group (X 2 = 0.08) and became significant when L (clinic SBP&lt;75 th %) was compared to M+H (clinic SBP &gt; 80 th %; X 2 =0.04). Daytime ABP index (subject daytime systolic ABP/95 th % for daytime systolic ABP) and BMI z-score (both p &lt; 0.003) were significantly associated with nTOD in a model containing clinic SBP, age, sex and race (other covariates NS; full model p &lt; 0.0001, R 2 =0.22). We conclude that higher ABP is associated with a greater number of cardiac and vascular abnormalities in youth. ABP should be applied in youth with elevated BP to evaluate need for intensification of therapy to prevent CV TOD.

Hypertension defined by the 2017 ACC/AHA guideline is more accurate than 2018 ESC/ESH for detecting early vascular aging in young adults.

Determine the most accurate diagnostic criteria of arterial hypertension (AH) for detecting early vascular aging (EVA) defined by pulse wave velocity (PWV) higher than ≥9.2 m/s.Cross-sectional study of a birth cohort started in 1978/79. The following data were collected between April 6, 2016 and August 31, 2017 from 1775 participants: demographic, anthropometric, office blood pressure (BP) measurement, biochemical risk factors, and PWV. A subsample of 454 participants underwent 24-hour ambulatory BP monitoring. The frequencies of AH, and BP phenotypes were calculated according to both guidelines. BP phenotypes (white-coat hypertension, masked hypertension (MHT), sustained hypertension (SH) and normotension) were correlated with risk factors and subclinical target organ damage after adjustment for confounders by multiple linear regression. Receiver operating characteristic curves were constructed to determine the best BP threshold for detecting EVA.A higher frequency of AH (45.1 vs 18.5%), as well as of SH (40.7 vs 14.8%) and MHT (28.9 vs 25.8%) was identified using the 2017 ACC/AHA criteria comparing with 2018 ESC/ESH. EVA was associated with the higher-risk BP phenotypes (SH and MHT, P < .0001) in both criteria. There was a higher accuracy in diagnosing EVA, with the 2017 ACC/AHA criteria. Analysis of the receiver operating characteristic curves showed office BP cutoff value (128/83 mm Hg) for EVA closer to the 2017 ACC/AHA threshold.The 2017 AHA/ACC guideline for the diagnosis of AH, and corresponding ambulatory BP monitoring values, is more accurate for discriminating young adults with EVA. Clinical application of PWV may help identify patients that could benefit from BP levels <130/80 mm Hg.

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&amp;lt;0.001, Figure), PWV (r=0.277, p&amp;lt;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&amp;gt;115 g/m2 in men and &amp;gt;95 g/m2 in women), increased PWV (PWV&amp;gt;10m/s), decreased ABI (ABI&amp;lt;0.9) and decreased renal function (eGFR&amp;lt;60ml/min)]. Specifically, ACR exhibited significant association with the number of TOD and this association was independent of age and gender (p&amp;lt;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. Funding Acknowledgement Type of funding sources: None. Association between LVMI and ACR

Abstract P119: Cardiovascular Risk And Subclinical Target Organ Damage In A Young Adult Population Provided By A Primary Healthcare Center In Brazil (Laparc Study)

Background: In this young and apparently healthy population, it is important to identify early CV risk factors and subclinical target organ damage (TOD) with low complexity procedures, aiming regression, control and primary prevention with future reduction of CV morbidity and mortality. Objectives: To evaluate subclinical TOD using Ankle-Brachial Index (ABI), Office and Home Pulse Pressure (PP), identifying arterial stiffness. Methods: A cross-sectional population study for CV risk assessment in adults aged 20-50 years old provided by a Primary Healthcare Center in Brazil. A total of 632 individuals were evaluated (40% male; mean age 36 ± 9 years). Socio-demographic, anthropometric data, and lifestyle evaluation were recorded. All underwent Office Blood Pressure (OBP) measurements in the 4 limbs to calculate the ABI and office PP. All received the Home Blood Pressure Monitoring (HBPM) device (7 days protocol) and the mean of the general BP and the calculation of the PP were evaluated. They also performed an ECG to calculate Sokolow-Lyon Index (SLI) and Cornell Voltage Index (CVI). Results: The prevalence of hypertension according to OBP was 16% and 18% according to HBPM, but with a low agreement between diagnoses (kappa = 0.385). HBPM identified 4 phenotypes: normotension (74%), sustained hypertension (8%), masked hypertension (10%), and white coat hypertension (8%). The median of office PP was 46 [39-52] mmHg and of Home PP was 45 [41-50] mmHg. Elevated Office PP and Home PP (&gt; 60 mmHg) were identified in 64 and 28 participants, respectively. High office PP was more frequent in men, obese, with increased neck circumference and lower ABI. It was also associated with higher SLI and CVI. High Home PP was also more frequent in men, obese, with increased neck circumference and higher CVI. The median of the ABI was 1.14 [1.08-1.22], which is the cutoff point we used to define early changes in the ABI. Individuals with decreased ABI are more obese, with smaller neck circumference and lower OBP control. They also had higher systolic BP values and office PP (49 vs 43 mmHg, p&lt;0.001). Conclusion: In this young population, early changes in subclinical TOD already identify a higher CV risk profile, indicating the importance of implementing prevention measures to reduce this risk.

Abstract MP44: A Novel And 2 Known Differentially Expressed MicroRNAs Were Identified In Peripheral Blood Mononuclear Cells Of Patients With Hypertension Associated With Metabolic Syndrome

Background: Hypertension (HTN) is associated with subclinical target organ damage including cardiac, vascular and kidney injury. The immune system plays a role in hypertension and target organ damage. Activation of T cells has been reported among peripheral blood mononuclear cells (PBMCs) of patients with HTN. MicroRNAs (miRNAs) are crucial post-transcriptional regulators of immune cells. Whether miRNAs play a role in the activation of immune cells in hypertension complicated by target organ damage in humans remains unknown. We aimed to address this question by identifying differentially expressed (DE) miRNAs and their mRNA targets in PBMCs of patients with hypertension complicated or not with metabolic syndrome (MetS) or chronic kidney disease (CKD). Methods: Normotensive subjects and patients with hypertension (HTN) associated or not with at least 2 other features of MetS or CKD were studied (n=15-16). PBMCs were isolated from blood, RNA extracted for small and total RNA sequencing (RNA-seq) using Illumina HiSeq-2500 and data were analyzed using a systems biology approach. MiRDeep2 was used for novel miRNAs prediction, miRNA annotation and counting. TargetScan 7.07 was used to predict DE miRNA targets with weighted context score percentile &gt;50%. DE genes miRNAs and mRNAs were identified with fold change (FC) &gt;1.5 and P &lt;0.005. DE miRNAs with FC&gt;2 and mean read count number (MRCM) &gt;500, and with predicted targets with MRCM&gt;300 were validated by reverse transcription-quantitative PCR (RT-qPCR). Results: DE miRNAs, mRNAs and non-coding RNAs were identified in HTN (22, 19 and 0), MetS (57, 401 and 11) and CKD (6, 26 and 2) compared to NTN. TargetScan predicted that 7 miRNAs target 3 mRNAs in NTN, 57 miRNAs target 55 mRNAs in MetS and 3 miRNAs target 2 mRNAs in CKD. DE miR-409-5p (FC: 0.54±0.10 vs 1.00±0.09, P &lt;0.05), miR-411-5p (FC: 0.40±0.06, vs 1.00±0.11, P &lt;0.001) and the novel miR-pl-86 (FC: 1.96±0.17 vs 1.00±0.15, P &lt;0.05) in MetS vs NTN were validated by RT-qPCR. RNA-seq data were correlated with RT-qPCR for miR-409-5p (R 2 =0.40, P &lt;2.4E-07, n=55), miR-411-5p (R 2 =0.55, P &lt;1.1E-10, n=55), miR-pl-86 (R 2 =0.37, P &lt;5.5E-07, n=56). Conclusion: This study showed that DE miR-409-5p, miR-411-5p and miR-pl-86 may play a role in HTN associated with MetS.

DIFFERENTIALLY EXPRESSED MICRORNAS AND THEIR TARGETS WERE IDENTIFIED IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF PATIENTS WITH HYPERTENSION ASSOCIATED OR NOT WITH TARGET ORGAN DAMAGE

Objective: Hypertension is associated with subclinical target organ damage including cardiac, vascular and kidney injury. The immune system plays a role in HTN and target organ damage in animal models. Activation of T cells has been reported among peripheral blood mononuclear cells (PBMCs) of patients with HTN. MicroRNAs are crucial post-transcriptional regulators of immune cells. Whether microRNAs play a role in the activation of immune cells in HTN complicated by target organ damage in humans remains unknown. We aimed to address this question by identifying differentially expressed (DE) microRNAs and their mRNA and non-coding RNA (ncRNA) targets in PBMCs of patients with HTN complicated or not with target organ damage. mRNA targets of DE microRNAs were predicted with TargetScan using the inversely related DE mRNAs as a filter to improve prediction efficiency. Design and method: Normotensive (NTN), hypertensive patients (HTN) and patients with HTN associated with at least 2 other features of the metabolic syndrome (MetS) or with chronic kidney disease (CKD) grades 3-4 were studied (n = 15-16 in each group). PBMCs were isolated from blood, RNA extracted for RNA sequencing (RNA-seq) using Illumina HiSeq-2500 and data were analyzed using a systems biology approach. DE genes microRNAs and mRNAs were identified with fold change (FC) &gt;1.5 and P &lt; 0.005. DE miRNAs with FC &gt;2 and RNA-seq count number (CM) &gt;500, and with predicted targets with CM &gt;300 were validated by reverse transcription-quantitative PCR (RT-qPCR). Results: DE microRNAs, mRNAs and other ncRNAs were identified by RNA-seq in HTN (22, 19 and 0), MetS (57, 401 and 11) and CKD (6, 26 and 2) compared to NTN. TargetScan predicted that 7 microRNAs target 3 mRNAs in NTN, 57 microRNAs target 55 mRNAs in MetS and 3 microRNA target 2 mRNAs in CKD. Three of 14 selected miRNAs were validated by RT-qPCR: miR-409-5p (46% down, P &lt; 0.05) and miR-411-5p (60% down, P &lt; 0.001) and novel miR-pl-86 (2-fold up, P &lt; 0.05) in MetS vs NTN. Conclusions: RNA-seq and RT-qPCR validation showed that DE miR-409-5p, miR-411-5p and the novel miR-pl-86 may play a role in HTN associated with MetS.

RELATIONSHIP AMONG ARTERIAL STIFFNESS PARAMETERS AND TARGET ORGAN DAMAGE

Objective: Carotid-femoral (cf) PWV is considered the gold standard for arterial stiffness (AS) but other different parameters can add information about systemic or local AS. Whether that information is clinically redundant or complementary is currently unknown. We analyzed the relationship among different AS parameters to each other and with a target organ damage (TOD) score. Design and method: AS data were retrospectively evaluated in a sample of 1031 hypertensive patients. Cf-PWV and Augmentation index (Aix) by peripheral applanation tonometry (PAT) were determined with an SphygmoCor® device. Local PWV, local Aix, Ep module, Beta parameter and arterial compliance were determined by echo-tracking at the carotid level with an Aloka ultrasound (US) device. Left ventricular mass (LVM) was assessed by echocardiography, intima-media thickness (IMT) and plaques by carotid US and albumin-creatinine ratio (ACR) by immunonephelometry. A 24 points subclinical target organ damage (TOD) score was created using not only qualitative (presence or absence) but also quantitative information (magnitude of damage). The relationship among parameters of AS to each other and with the score of TOD were established by Pearson or Spearman correlation coefficients. Results: There was a significant relationship between cfPWV and the score of subclinical TOD, the higher the score, the higher the PWV (r = 0.19, p-value &lt; 0.05). All echo-tracking parameters, particularly the Ep module were also significantly related to the score but not the Aix by PAT. There were significant correlations among the different measures of AS to each other. The highest correlation was found between the Aix determined by tonometry and local Aix determined by carotid echo-tracking (r = 0.71, p-value &lt; 0.05). By contrast the correlation between the cfPWV and local carotid PWV was very low (r = 0.28, p-value &lt; 0.05). Conclusions: There was a significant correlation among different AS parameters and probably these parameters may add extra information to the gold standard (cfPWV). The presence of an increase in AS parameters is linearly related with the presence of subclinical TOD at other levels. Further studies are needed to determine the clinical prognostic values of combined AS parameters.

LOWER CIRCULATING MIR-191-5P AND LET-7G-5P ARE INDEPENDENT BIOMARKERS OF RENAL INJURY

Objective: Hypertension is associated with subclinical target organ damage including cardiac, vascular and kidney injury. Circulating microRNAs have been investigated as biomarkers of cardiovascular disease, but few studies have examined them as target organ damage biomarkers in hypertension. We aimed to identify circulating microRNAs that could serve as biomarkers of hypertension-induced target organ damage using an unbiased approach. Design and method: Normotensive subject, hypertensive patients (HTN) and patients with HTN associated with at least 2 other features of the metabolic syndrome (MetS) or with chronic kidney disease (CKD) grades 3–4 were studied (n = 15–16). Blood pressure was determined by automated office measurement (AOBP). Blood and urine were collected for determination of blood cell count, blood biochemistry and urinalysis. Platelet-free plasma (6 mL) was isolated from blood collected on EDTA, and RNA extracted for small RNA deep sequencing using Illumina HiSeq-2500. Differentially expressed (DE) genes were identified with a threshold of false discovery rate &lt; 0.1. The most abundant DE miRNAs were confirmed by reverse transcription-quantitative PCR (RT-qPCR). Right common carotid artery remodeling and stiffness were assessed by ultrasound and aorta stiffness by carotid to femoral pulse wave velocity. Results: We found 4 up-regulated and 4 down-regulated miRNAs uniquely associated with the HTN group, 1 up-regulated uniquely associated with the MetS group, 1 up-regulated and 12 down-regulated miRNAs uniquely associated with the CKD group and 8 were found similarly DE in different groups (P &lt; 0.01 and q &lt; 0.1). Two down-regulated miRNAs, let-7g-5p and miR-191–5p of 11, the most abundant DE miRNAs, were validated by RT-qPCR. Correlation analysis revealed that let-7g-5p was associated with large vessel stiffening, miR-191–5p with diabetes, and both microRNAs with estimated glomerular filtration rate (eGFR) and inflammatory markers. Using let-7g-5p and miR-191–5p and parameters that correlated with eGFR as candidate variables, stepwise multiple linear regression generated a model showing that let-7g-5p, miR-191–5p and urinary albumin/creatinine ratio predicted eGFR with an adjusted R2 of 0.40 (P = 1.1e-5). Conclusions: Circulating let-7g-5p and miR-191–5p were identified as independent biomarkers of chronic kidney disease among patients with hypertension, which could have pathophysiological and therapeutic implications.

Uric Acid Associates With Executive Function in Children and Adolescents With Hypertension.

[Figure: see text].