S. Obregon

Sympathetic predominance is associated with impaired endothelial progenitor cells and tunneling nanotubes in controlled-hypertensive patients

Early endothelial progenitor cells (early EPC) and late EPC are involved in endothelial repair and can rescue damaged endothelial cells by transferring organelles through tunneling nanotubes (TNT). In rodents, EPC mobilization from the bone marrow depends on sympathetic nervous system activity. Indirect evidence suggests a relation between autonomic derangements and human EPC mobilization. We aimed at testing whether hypertension-related autonomic imbalances are associated with EPC impairment. Thirty controlled-essential hypertensive patients [systolic blood pressure/diastolic blood pressure = 130(120-137)/85(61-88) mmHg; 81.8% male] and 20 healthy normotensive subjects [114(107-119)/75(64-79) mmHg; 80% male] were studied. Mononuclear cells were cultured on fibronectin- and collagen-coated dishes for early EPC and late EPC, respectively. Low (LF)- and high (HF)-frequency components of short-term heart rate variability were analyzed during a 5-min rest, an expiration/inspiration maneuver, and a Stroop color-word test. Modulations of cardiac sympathetic and parasympathetic activities were evaluated by LF/HF (%) and HF power (ms(2)), respectively. In controlled-hypertensive patients, the numbers of early EPC, early EPC that emitted TNT, late EPC, and late EPC that emitted TNT were 41, 77, 50, and 88% lower than in normotensive subjects (P < 0.008), respectively. In controlled-hypertensive patients, late EPC number was positively associated with cardiac parasympathetic reserve during the expiration/inspiration maneuver (rho = 0.45, P = 0.031) and early EPC with brachial flow-mediated dilation (rho = 0.655; P = 0.049); also, late TNT number was inversely related to cardiac sympathetic response during the stress test (rho = -0.426, P = 0.045). EPC exposure to epinephrine or norepinephrine showed negative dose-response relationships on cell adhesion to fibronectin and collagen; both catecholamines stimulated early EPC growth, but epinephrine inhibited late EPC growth. In controlled-hypertensive patients, sympathetic overactivity/parasympathetic underactivity were negatively associated with EPC, suggesting that reducing sympathetic/increasing parasympathetic activation might favor endothelial repair.

Sodium Intake Is Associated With Parasympathetic Tone and Metabolic Parameters in Mild Hypertension

BACKGROUND Although the impairment of parasympathetic cardiac control was described in hypertensives submitted to a high salt diet, the impact of this autonomic abnormality on metabolic and inflammation markers in patients with mild hypertension has not been explored. METHODS Four hundred and ninety mild essential hypertensive patients (144 ± 9/94 ± 9 mm Hg, 49.5 ± 13.9 years, 67.9 % male) were studied. Dietary sodium intake was estimated by measuring 24-h urinary sodium excretion (UNa), and the patients were classified according to UNa levels as follows: low (<50 mEq/l), medium (50-99 mEq/l), and high UNa (≥100 mEq/l). Parasympathetic tone was evaluated by assessing heart rate recovery (HRR) after an exercise stress test. HRR, plasma lipids, glucose metabolism, and inflammatory biomarkers were compared across UNa groups. RESULTS HRR and high-density lipoprotein (HDL)-cholesterol were progressively lower, and insulin (INS), homeostasis model assessment of insulin resistance (HOMAir), ultrasensitive-C-reactive protein (usCRP) were progressively higher across increasing UNa groups. In the low and medium UNa groups, HDL-cholesterol was higher and CRP was lower than that in high UNa (P < 0.01 and P < 0.05, respectively) (Dunnett post-hoc test). In the low UNa group, triglycerides (TGs), INS, and HOMAir were lower than that in high UNa (P < 0.05). Multiple linear regression analysis showed that UNa, HOMAir, and heart rate (HR) were negatively associated with HRR (P < 0.0001, P < 0.0001, and P = 0.001, respectively). CONCLUSIONS In the essential hypertensive patients studied high sodium intake is associated with parasympathetic inhibition, lipid disturbances, and inflammation. Studies designed to assess causality between sodium intake and metabolic and autonomic status are needed to evaluate the relevance of controlling sodium intake, especially in hypertensive patients.

Are plasma renin activity and aldosterone levels useful as a screening test to differentiate between unilateral and bilateral renal artery stenosis in hypertensive patients

Objective To evaluate the serum aldosterone (Ald)/plasmatic renin activity (PRA) ratio as a surrogate marker of renin–angiotensin–aldosterone system status in unilateral (Uni)- and bilateral (Bi)-renal artery stenosis (RAS). Methods Seven hundred and eight hypertensive patients (HTP) were studied. Intermediate and high pretest risk of RAS was detected in 66 HTP who subsequently underwent renal gadolinium-enhanced magnetic resonance and arteriography. After application of exclusion criteria 51 HTP remained: 16 with Uni-RAS, 16 with Bi-RAS and 19 essential hypertensives with normal arteries. Nineteen normotensive individuals were also studied. Ald and PRA were determined before and after stenosis resolution by balloon angioplasty and stent implantation. Results Ald/PRA (ng/dl per (ng/ml per h−1)) was markedly high in Bi-RAS (5.92 ± 2.30, P < 0.001), and markedly low in Uni-RAS (0.38 ± 0.17, P < 0.001) versus essential hypertensives (1.52 ± 2.02). Multilevel likelihood ratios for Bi-RAS were positive for Ald/PRA higher than 3.6, negative for Ald/PRA lower than 0.2, and neutral for Ald/PRA at least 0.2 and 3.6 or less. ROC analysis identified Ald/PRA lower than 0.5 and Ald/PRA higher than 3.7 to have the best sensitivity and specificity to detect Uni-RAS and Bi-RAS, respectively. In Uni-RAS, but not in Bi-RAS, postinterventional PRA was significantly lower than basal PRA. In Uni-RAS and Bi-RAS, postinterventional Ald was approximately 30% and approximately three times lower than basal Ald, respectively. In essential hypertensives, PRA and Ald showed no changes in the same period. Conclusion In the population studied, Ald, PRA and Ald/PRA were significantly different among essential hypertensives, and HTP with Uni-RAS or Bi-RAS. Studies with a higher number of patients will allow exploration of the usefulness of pharmacologic aldosterone blockade in Bi-RAS, and to assess the relevance of Ald/PRA to differentiate Uni-RAS from Bi-RAS.

Lack of RAAS inhibition by high-salt intake is associated with arterial stiffness in hypertensive patients

Hypothesis/introduction: The relationship between salt intake, blood pressure and RAAS activation is still controversial, being that both high- and low-salt intakes are associated with cardiovascular events in a J-shaped curve pattern. We hypothesized that different patterns of RAAS response to dietary salt intake among hypertensives could be identified, while vascular damage would be related to high-salt intake plus absence of expected RAAS inhibition. Objective: We aim to assess the relationship between sodium intake, RAAS and vascular stiffness in hypertension. Materials and methods: We screened 681 hypertensive patients for urinary/plasma electrolytes, renin, aldosterone and pulse wave velocity (PWV) under their usual salt intake level. Results: After applying exclusion criteria, an inverse relation between urinary sodium and RAAS was observed in the 300 remaining subjects. Additionally, four types of response were identified: 1) Low (L) sodium (S)-Low RAAS, 2) LS-High (H) SRAAS, 3) HS-Low RAAS, 4) HS-High RAAS. We found no differences in age/BP among groups, but type 4 response individuals included more females and a higher pulse wave velocity. Conclusions: We showed a) an inverse salt-RAAS relation, b) an association between HS plus high RAAS with increased PWV that could identify a higher-risk hypertensive condition.

DEPRESSION-MEDIATED ARTERIAL STIFFNESS AND AUTONOMIC DISBALANCE IN YOUNG HYPERTENSIVE PATIENTS: A PATHWAY TO STROKE?: PP.4.144

Systemic hypertension and depression are currently considered risk factors for cardio-cerebral-vascular disease and particularly for stroke. The mechanisms how depression increases the risk of stroke have not been fully elucidated. It is also well known that elevated pulse wave velocity (PWV) as evidence of arterial stiffness and target organ damage (TOD) increases risk of cerebral events. Furthermore, autonomic disbalance has been related as a physiopatological mechanism in depression and cardiovascular disease. Based on this unexplored issue, we explored the hyphotesis that the association between hypertension and depression is related to greater PWV increase, and that autonomic disbalance could be one of the pathways involved. Objective: To evaluate PWV and the autonomic balance in young hipertensive patients with depression. Methods: We studied 34 consecutive hypertensive patients (39 ± 9,1 years; 68 % men) admitted for TOD assessment. All patients completed voluntarily a sheet with two questions validated for depression screening and validated scales (CES-D/Hamilton) to obtain a severity score of depression. Arterial stiffness was determined by non-invasive PWV measurement and autonomic response by heart rate variability, previously described by others, during stress test recovery period. Results: This population was analyzed in a 2:1 ratio, classified as depressive (n:11) when at least one question was positive, and non-depressive (n:23) when both were negative. Results were analyzed with chi2 and T-test. There were no significative differences in baseline characteristics. Depressive patients showed a significative higher PWV (11 ± 2,1 vs 9,2 ± 1,6 m/s; p = 0.025). There was also found a difference in stress test recovery period, showing a faster recovery in the same group (p = 0.006). Figure 1. No caption available. Conclusions: An association between an increased arterial stiffness, autonomic disbalance and depression was found in the young hypertensive population we evaluated. Further studies would be necessary to identify their contribution to the increased risk of stroke previously reported (MRFIT/WHI). Autonomic disbalance could be a probable physiopathological pathway while arterial stiffness would be a marker of its early atherosclerotic impact.

Frequency of early vascular aging and associated risk factors among an adult population in Latin America : the OPTIMO study

The main objective was to estimate the frequency of early vascular aging (EVA) in a sample of subjects from Latin America, with emphasis in young adults. We included 1416 subjects from 12 countries in Latin America who provided information about lifestyle, cardiovascular risk factors (CVRF), and anthropometrics. We measured pulse wave velocity (PWV) as a marker of arterial stiffness, and blood pressure (BP) using an oscillometric device (Mobil-O-Graph). To determine the frequency of EVA, we used multiple linear regression to estimate each subject’s PWV expected for his/her age and systolic BP, and compared with observed values to obtain standardized residuals (z-scores). We defined EVA when z-score was ≥1.96. Finally, a multivariable logistic regression analysis was performed to determine baseline characteristics associated with EVA. Mean age was 49.9 ± 15.5 years, male gender was 50.3%. Mean PWV was 7.52 m/s (SD 1.97), mean systolic BP was 125.3 mmHg (SD 16.7) and mean diastolic BP was 78.9 mmHg (SD 12.2). The frequency of EVA was 5.7% in the total population, 9.8% in adults of 40 years or less and 18.7% in those 30 years or less. In these young adults, multiple logistic regression analyses demonstrated that dyslipidemia and hypertension showed an independent association with EVA, and smoking a borderline association (p  =  0.07). In conclusion, the frequency of EVA in a sample from Latin America was around 6%, with higher rates in young adults. These results would support the search of CVRF and EVA during early adulthood.

[PP.09.29] DISTRIBUTION OF CENTRAL AORTIC PRESSURE VALUES AND HIDDEN CENTRAL HYPERTENSION IN A LARGE COHORT OF ARGENTINA

Objective: The objetive is to determine the distribution of central aortic pressure values in a large cohort of Argentina, and the distribution of elevated central aortic pressure values in normotensives and controlled hypertensives. Design and method: From a large prospective cohort of 10300 subjects in a cardiovascular prevention programme (2013–2015), 8249 individuals were evaluated with central aortic pressure measurements (median arterial pressure calibration / Mobil-O-Graph, IEM, Germany). Associations with cardiovascular risk factors and other hemodynamic variables were performed in a group of 1473 normotensive people with complete clinical data, and also a group of 945 controlled hypertensives (bSBP/bDBP <140/90 mm Hg). Elevated aSBP was considered as 130 mm Hg or higher. Analysis of variables was performed with Excel 2016 and SPSS 22. Results: More than a half (53.3%) of the total population (54.5 ± 13.4 years; 61.2% male; bSBP/bDBP 128.8 ± 15.9/83.4 ± 11.4 mm Hg; cSBP/cDBP 132.8 ± 18.7/85 ± 11.8 mm Hg) were observed with an elevated aSBP (56.3 ± 13.8 years; 67.8% male; bSBP/bDBP 137.9 ± 14.5/87.9 ± 11.4 mm Hg; cSBP/cDBP 146.2 ± 14.5/90.1 ± 11.6 mm Hg). In normotensives (52.5 ± 11.7 years; 58.1% male; bSBP/bDBP 123 ± 9.8/81.2 ± 9.1 mm Hg; cSBP/cDBP 126.4  ± 14/82.6 ± 9.4 mm Hg), elevated aSBP was found in a proportion of 33.9% (53.6 ± 12.2 years; 69.8% male; bSBP/bDBP 129.3  ± 7/84.4 ± 8.6 mm Hg; cSBP/cDBP 139.5 ± 8.5/86.5 ± 8.9 mm Hg). In controlled hypertensives (52.5 ± 11.7 years; 67.7% male; bSBP/bDBP 123 ± 9.8/81.2 ± 9,1 mm Hg; cSBP/cDBP 126.4  ± 14/82.6 ± 9.4 mm Hg), 50% were observed with elevated aSBP (59.6 ± 10 years; 71.9% male; bSBP/bDBP 126.8 ± 9.1/83.6 ± 9 mm Hg; cSBP/cDBP 133.3  ± 13/85.5 ± 9.5 mm Hg). Conclusions: A large proportion of patients with elevated aSBP was observed in this population of Argentina, both in one third of normotensive patients and half of controlled hypertensives. This data contributes to considering the so called hidden central hypertension as a frequent clinical situation for future hypertension research and management.

[PP.25.01] RESILIENCE AND VASCULAR DISEASE: A NEW PARADOX

Objective: Resilience is the ability to adapt to adverse situations. The objective of our study was to evaluate patients with great resilience, verify their vascular risk and identify their epidemiological characteristics in cardiovascular disease. Could the resilience have a protective function in the disease development? Design and method: Patients participating in a cardiovascular prevention program were included in the study. Resilience condition and low, moderate and high statuses were assessed through the RS Wagnild & Young (WyY test. Arterial stiffness was determined by measurement of PWV (Mobil O Graph, IEM, Germany). Intima media thickness (IMT) was measured with ultrasonography. CV risk was estimated with ACC 2013 calculator. Age was split in 3 groups to verify if a link between resilience and age actually exists. Results: Population was 241p (55.06 ± 9.05 years old, 46% female), 161p (77%) presented high resilience status (HRS), and 80p presented moderate resilience status (MRS, 33%). Patients with HRS versus RSM had similar age 53.79 vs. 55.70 p 0.1178, greater ACC/2013 score (6,1 ± 0.3 vs 5,0 ± 0,7 p: = 0.00001), and Asymptomatic Carotid Diseases (ACD) (76p vs. 26p; p = 0.0296). After comparing the resilience in different age categories (40–55, 55–65 and greater than 66 years) the group = > 66 years had more RS (p 0,0188), personal competences (p 0.0313), life acceptance (p 0,0354). Also this group (= > 66 years) had a greater proportion of patients with a ACC cardiovascular risk score = > 7,5% (p 0,00001), high PWV (p.0,001), ACD (p 0,0026), IMT = > 0,9 MM (p 0,002) and vascular stiffness (VS) (p 0,0100). When considering the characteristics of the highly resilient patients adjusted by age and gender the results were: TABLE Figure. No caption available. Conclusions: Older subjects presented higher resilience. Contrary to our original hypothesis they presented higher cardiovascular risk, higher cardiovascular stiffness and higher vascular disease.

[PP.19.21] ASSOCIATION BETWEEN QTC AND VASCULAR STIFFNESS

Objective: QTc prolongation is associated with hypertension, insulin resistance, body mass index increase (BMI), left ventricular hypertrophy, female gender, and subclinical artheriosclerosis. Among hypertensives an increased arterial stiffness is considered as a subclinical target organ damage. Our hypothesis was that a direct association between QT interval duration and arterial stiffness could be identified suggesting their interaction towards a higher cardiovascular risk. Aims (a) To evaluate the distribution of corrected QTc duration in hypertensive patients (HP) in comparison with a control group and (b) to determine the association between QTc and vascular stiffness in the general population. Figure. No caption available. Design and method: The study included 53 patients considered as general population, and then classified as hypertensive (n: 30), and normotensive (n:23), age: 55,13 +/− 9,94 years, male: 34, female:19. Arterial pressure, vascular stiffness, index of left ventricular mass (LVMI) and QTc interval were measured. Patients were divided in tertiles according to the QTc duration: T1 QTc 350–400 msec, T2 QTc 400–439 msec and T3 QTc > 440 msec. Results: No major differences was observed between the hypertensive patients group and the control group in terms of age (p 0,0873), gender (p 0,6142), diabetes (p 0,8721), sedentary lifestyle (p 0,0650), and smoking (p 0,9121). Difference was observed in systolic blood pressure (SBP), p 0,00365, diastolic blood pressure (DBP) p 0,001 and QTc (406,10 +/− 29,6 versus 391,76 +/− 21,1 p 0,0345). Table 1 The QTc correlated in univariate form with PWV (p 0,0050) and with SBP (p 0,0328). When making a multivariate analysis the association between PWV and QTc remained unchanged (p 0, 0232). The AUC was 0,686 (p 0.0154), with a 83, 3% sensitivity, 58.54% specificity and a cut point of 402 mseg for QTc as predictor of vascular stiffness increase. Conclusions: The QTc values were more prolonged in hypertensive patients. Furthermore, a direct association between QTc length and arterial stiffness was observed.

[PP.21.30] ELEVATED PREVALENCE OF EARLY VASCULAR AGING IN YOUNG ADULTS IN LATIN AMERICA: A CALL FOR ACTION? OPTIMO STUDY RESULTS

Objective: Early Vascular Aging (EVA) represents an arterial wall damage at an earlier age than expected by natural aging. It is dominated by an increased arterial stiffness and predicts a high cardiovascular risk. Our main objective was to analyze the prevalence of EVA in a population of Latin America with emphasis in young adults. Design and method: recruited 1416 subjects from 13 countries in Latin America who provided information about lifestyle, cardiovascular risk factors and anthropometrics. We performed a measurement of pulse wave velocity (PWV) as a marker of arterial stiffness and blood pressure (BP), by use of Mobil-O-Graph. To determine the prevalence of EVA we estimated PWV adjusted by age and systolic BP in a multiple linear regression model and compared expected versus observed PWV. Then, we analyzed standardized residuals (z-scores) of adjusted PWV applying Observed PWV - Expected PWV / SD of Expected PWV. We defined EVA when z-score was > = 1.96. Finally, we performed multivariable logistic regression analysis to determine variables associated to EVA in all the subjects and in young adults (<41 years-old). Results: Mean age was 49.9 ± 15.5 years-old, male gender was 50.3%. Mean PWV was 7.52 m/s (+−1.97) and mean systolic BP was 125.29 mmHg (+−16.78). Z-score analyses determined that observed PWV values were predicted by age and systolic BP in 1272 subjects (89.8%). The remaining 81 (5.7%) cases represent the observed prevalence of EVA and 63 (4.4%) the prevalence of low PWV. Prevalence of EVA restricted to adults <41 years-old was 9.8% (37/376) and <31 years-old was 18.7% (30/160). Multiple logistic regression analysis showed that dyslipidemia, hypertension and regular alcohol intake (p < 0.05) were independently associated to EVA in young adults. Body mass index showed a borderline association (p = 0.06). Conclusions: After adjusting PWV for age and systolic BP, the observed prevalence of EVA in young adults in Latin America was very high, around 1 out of 10 and 1 out of 5 in those who were 40 and 30 years old or less, respectively. These results call for efforts to investigate, diagnose and treat cardiovascular risk factors from youth.