Prevalence and Burden of Carotid and Femoral Atherosclerosis in Subjects Without Known Cardiovascular Disease in a Large Community Hospital in South-America.

INTRODUCTION: Clinical guidelines recommend measurement of arterial (carotid and femoral) plaque burden by vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk without known atherosclerotic cardiovascular disease (ASCVD). AIM: To evaluate the prevalence of carotid and femoral plaques by age and sex, the burden of subclinical atherosclerosis (SA), and its association with classic CVRF in subjects over 30 years of age without ASCVD. METHODS: We prospectively enrolled 5775 consecutive subjects referred for cardiovascular evaluation and determined the prevalence and burden of SA using 2D-VUS in carotid and femoral arteries. RESULTS: Sixty-one percent were men with a mean age of 51.3 (SD 10.6) years. Overall, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. The prevalence of plaques and SA burden showed an increasing trend with age, being higher in men than in women and starting before the age of 40, both in the carotid and femoral sites. There was also an increasing prevalence of plaques according to the number of CVRF, and interestingly we found a high prevalence of plaques in subjects with 0 or 1 classic CVRF. CONCLUSIONS: We observed an increased prevalence and burden of carotid or femoral SA, higher in men, beginning before the fourth decade of life and increasing with age. Despite a significant association with classic CVRF, a significant number of subjects with low CVRF were diagnosed with SA.

Blood pressure control is not enough to normalize endothelial repair by progenitor cells.

Patients presenting with classical cardiovascular risk factors within acceptable or average value ranges often develop cardiovascular disease, suggesting that other risk factors need to be considered. Considering that endothelial progenitor cells (EPCs) contribute to endothelial repair, we investigated whether EPCs might be such a factor. We compared the ability of peripheral blood EPCs to attach to extracellular matrix proteins and to grow and function in culture, between controlled hypertensive patients exhibiting a Framingham score (FS) of <10% while showing severe vascular impairment (intima-media thickness/diameter, carotid-femoral pulse wave velocity, brachial artery flow-mediated dilation, carotid and femoral atherosclerotic plaque presence; vulnerable group, N = 30) and those with an FS of ≥10% and scarce vascular changes (protected group, N = 30). When compared with vulnerable patients, protected patients had significantly higher early and late-EPC and early and late-tunneling nanotube (TNT) numbers. Significant negative associations were found between vascular damage severity and early EPC, late-EPC, or late-TNT numbers, whereas EPC or TNT numbers and patient characteristics or cardiovascular risk factors were not associated. Except for protected patients, in all controlled hypertensive patients, early and late-EPC and early and late-TNT counts were significantly lower than those in the normotensive subjects studied (N = 30). We found that the disparity in vascular status between patients presenting with both an FS of ≥10% and scarce vascular changes and those presenting with both an FS of <10% and severe vascular impairment is related to differences in peripheral blood EPC and TNT numbers. These observations support the role of EPCs as contributors to vascular injury repair and suggest that EPC numbers may be a potential cardiovascular risk factor to be included in the FS calculation.NEW & NOTEWORTHY As individuals who present with risk factors within acceptable or average value ranges often develop cardiovascular (CV) disease, it has been suggested that other CV risk factors need to be considered in addition to those that are commonly combined in the Framingham score (FS) to estimate the risk of general CV disease. We investigated whether peripheral endothelial progenitor cells (EPCs) and tunneling nanotubes (TNTs) deserve to be considered. Here we report that EPCs and TNTs are significantly lower in controlled hypertensive patients versus normotensive subjects and that the disparity in vascular status between patients presenting with an FS of ≥10% with scarce vascular changes and those presenting with an FS of <10% with severe vascular impairment is related to differences in EPC and TNT numbers. These data point to EPC and TNT numbers as potential CV risk factors to be included in the FS calculation.

Improved identification of secondary hypertension: use of a systematic protocol.

BACKGROUND: The accurate identification and diagnosis of secondary hypertension is critical, especially while atherosclerotic cardiovascular heart disease continues to be the leading cause of death in the industrialized world. Nevertheless, despite the existence of diagnostic tools, there are significant variations of the estimated prevalence of secondary hypertension, due to multiple etiologies and suboptimal recognition. This study demonstrates the results of using a systematic and protocolled approach to improve recognition of the presence of secondary hypertension. In the future, this questionnaire can be a quick and effective tool to unveil secondary hypertension in a broad array of clinical settings. METHODS: A total of 28,633 consecutive patients from January 1, 2007 to January 1, 2017 were diagnosed as having primary or secondary hypertension, utilizing the International Code of Diseases. Patients were located at the Center of Hypertension, Institute of Cardiology at Austral University Hospital, Buenos Aires, Argentina and were then further classified as having TRH, or non-resistant hypertension, to which a systematic protocol was employed in search for secondary hypertension. The confirmation of secondary hypertension was subsequently confirmed by diagnostic laboratory and imaging techniques in a hospital setting. RESULTS: A final population of 12,284 patients with treatment resistant hypertension (TRH) and non-treatment resistant hypertension (NTRH) were included in this study, where an etiology of secondary hypertension was identified in 50.9% and 36% of patients in each treatment group, respectively. Physicians used confirmatory laboratory testing and imaging of patients who were identified as having a cause for their secondary hypertension, with no significant differences in sex, age and body mass index (BMI) among study groups. CONCLUSIONS: These results illustrate the prevalence and distribution of the causes of secondary hypertension using a systematic, protocolled approach, which revealed a higher percentage of secondary hypertension than previously reported. This tool may be used by healthcare providers to ensure the appropriate recognition of secondary causes of hypertension in a wider range of patients with high blood pressure beyond resistant hypertension, changing the diagnostic paradigm of this condition.

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.

Estimación del riesgo de somatización en pacientes hipertensos / Estimation of the Risk of Somatization in Hypertensive Patients

Introducción: La somatización en el paciente hipertenso afecta no solo su calidad de vida, sino también su adherencia al tratamiento y la relación médico-paciente, constituyéndose en un problema sanitario de alto costo, por lo que la posibilidad de determinar el riesgo de somatizar en estos pacientes podría favorecer un manejo individualizado de sus manifestaciones. Objetivos: Estratificar en una cohorte de hipertensos esenciales el riesgo de somatización y caracterizar las variables hemodinámicas asociadas. Material y métodos: Se analizaron de manera prospectiva 120 individuos que asistieron para la evaluación de su riesgo cardiovascular, que se clasificaron en: 1) grupo de hipertensos controlados (HTC) (57%, n = 68) y 2) grupo control de normotensos (NT) (43%, n = 52). El riesgo de somatización se evaluó con el inventario de síntomas SCL-90-R y las escalas de depresión y ansiedad. El perfil hemodinámico se determinó con un método oscilométrico validado. Resultados: El riesgo de somatización fue más elevado en el grupo HTC de manera independiente de la presencia de otras alteraciones emocionales. Los individuos con mayor riesgo de depresión y/o ansiedad presentaron mayor evidencia de somatización (p < 0,0001). En los HTC tratados (n = 38) se observó mayor riesgo de somatización y de trastornos del sueño respecto de los HTC sin tratamiento. El índice de masa corporal se asoció con el riesgo de somatización (p = 0,0227) y el género femenino mostró que es predictivo de somatización, ansiedad y depresión (p = 0,001). Se observó una relación directa entre el gasto cardíaco y depresión y somatización y entre el riesgo de somatización y el producto de la frecuencia cardíaca por la presión arterial sistólica en reposo. Conclusiones: Los resultados muestran la factibilidad de estimar el riesgo de somatización a través de una herramienta validada y reproducible. Los síntomas de consulta frecuente en esta condición podrían estar asociados con un riesgo incrementado de somatización, especialmente vinculado al género femenino, el índice de masa corporal, el tratamiento farmacológico, la presencia de alteraciones emocionales como depresión y ansiedad y el patrón hiperdinámico.

Background: Somatization in hypertensive patients affects not only their quality of life but also their adherence to treatment and the physician-patient relationship, constituting an expensive health care issue. The possibility of estimating the risk of somatization in these patients could promote an individualized management of their manifestations. Objectives: The goal of this study was to stratify the risk of somatization in a cohort of patients with essential hypertension and to characterize the hemodynamic variables associated with the risk of somatization in hypertensive patients. Methods: A total of 120 subjects undergoing cardiovascular risk assessment were prospectively analyzed and classified in: 1) controlled hypertensive group (CHT) (57%, n=68) and 2) normotensive group (NT) (43%, n=52). The risk of somatization was evaluated using the SCL-90-R symptom ckecklist, and the anxiety and depression scales. The hemodynamic profile was determined using a validated oscillometric method. Results: The risk of somatization was higher in the CHT group independently of the presence of other emotional disorders. In subjects with higher risk of depression or anxiety, the evidence of somatization was greater (p<0.0001). In the CHT group, those who received treatment (n=38) had greater risk of somatization and of sleep disorders compared to those without treatment in the same group. Body mass index was associated with the risk of somatization (p=0.0227) and female sex was a predictor of somatization, anxiety and depression (p=0.001). A direct relationship was observed between cardiac output and depression and somatization, and between the risk of somatization and the product of heart rate and systolic blood pressure at rest. Conclusion: The estimation of the risk of somatization is feasible using a validated and reproducible tool. The frequently consulted symptoms in this condition could be associated with a higher risk of somatization, particularly linked with female sex, body mass index, drug therapy, presence of emotional abnormalities a depression and anxiety, and an hyperdynamic pattern.

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.

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.

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.