M. Koretzky

Can the cold pressor test predict future cardiovascular events in patients without demonstrated ischemic heart disease by SPECT

OBJECTIVE To assess whether a cold pressor test (CPT) could help identify patients at a high risk of cardiovascular events in a population without known coronary artery disease (CAD) with a normal myocardial perfusion scintigraphy (MPS). METHODS Our population consisted of 870 patients with a mean age of 59.3years with several CAD risk factors, having been referred for an MPS. The CPT was performed between the third day and fifth day after the MPS. RESULTS The CPT was positive in 38.2% of the patients. After a mean 40-month follow-up, the patients were contacted to check for cardiac death, non-fatal myocardial infarction, and myocardial revascularization procedures. The event-free survival rates were 98.1% and 90.4% after a negative or positive CPT, respectively (p=0.0001). The positive CPT group exhibited a fourfold increased risk of CV events. All CV events in the negative CPT group occurred after a 30-month follow-up. The risk of CV events was 4.5 times higher in diabetic patients. CONCLUSION A positive CPT in patients with a negative MPS could help identify a subgroup of patients at a higher risk of developing symptomatic CAD. PRACTICE IMPLICATIONS Our results suggest that after a normal post-exercise MPS, patients should undergo a CPT.

[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.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.

[OP.1B.03] IDENTIFICATION OF A CUT-OFF LEVEL OF URIC ACID ASSOCIATED WITH VASCULAR STIFFNESS IN A GENERAL POPULATION.

Objective: The role of uric acid (UA) in the development of hypertension and atherosclerosis has been extensively studied. In regard to vascular stiffness, UA has demonstrated an independent association with age, gender, obesity, blood pressure and renal function. However, research has focused on the relationship between UA elevation and high blood pressure or atherosclerosis in hypertensive and renal failure patients. Recent data from the Framingham cohort, showed that this association persists in the general population. However there is no clear evidence of the cutoff level above which UA has a predictive value for vascular stiffness. Objective: To evaluate the relationship between UA and vascular stiffness in a general population, and to determine the cutoff level of serum uric acid for this association. Design and method: We recruited consecutively individuals without previous cardiovascular events, who attended a medical center for cardiovascular risk assessment. A blood sample was obtained and vascular stiffness was determined by the measurement of pulse wave velocity (PWV) using the Mobil-O-Graph (Germany). We excluded those diagnosed with gout, diabetes, renal failure, malignancies, and use of drugs for hyperuricemia. The population was categorized in quartiles of uric acid and PWV. The association of PWV and UA was explored by adjusted multiple regression. The cut-off level for the association of UA and PWV (abnormal vascular stiffness >=10 m/sec) was determined by ROC curve analysis (sensitivity - [1-specificity]). Results: We included 129 subjects (age 52.5 ± 13.8 years, 40% women). Mean serum UA was 333.09 ± 220.08 mMol/L, and the PWV averaged 8.9 ± 4.5 m/sec. The association between UA and PWV remained independent after adjusting for body mass index, smoking and blood pressure. Finally the best cutoff level for UA associated with the highest quartile of PWV was 458 mMol/L (discrimination value of 0.7). Conclusions: We observed a significant association between UA and vascular stiffness in a general population. The serum UA cut-off point was 458 mMol/L. These results encourage lines of research aimed at reducing UA levels in order to improve arterial stiffness.

[PP.37.08] HEALTHY LIFESTYLE IS ASSOCIATED WITH LOWER RISK OF EARLY VASCULAR AGEING: THE OPTIMO STUDY IN LATIN AMERICA

Objective: Early Vascular Ageing (EVA), dominated by increased arterial stiffness, is a cardiovascular risk marker. Our aim was to elucidate on lifestyle factors associated with EVA in diverse populations across Latin America. Design and method: A total of 1044 city inhabitants (51.3% men, mean age 50.3 ± 15.3 years) underwent a health screening examination in 12 countries in Latin America (Argentina, Brazil, Chile, Colombia, Costa Rica, Guatemala, Honduras, México, Nicaragua, Panamá, República Dominicana, Salvador). This included anthropometrics, a questionnaire on lifestyle (WHO STEPS survey), medical history, and measurement of pulse wave velocity (PWV) for arterial stiffness (Mobil-O-Graph device). PWV values were transformed into age-specific z-scores to identify subjects with greater than age-peers PWV values, here defined as EVA. Age groups were defined based upon age quartiles of the study population (Q1: <42, Q2: 42–51, Q3: 52–60, and Q4: 61+ years). Within each age quartile, a z-score was defined as (individual PWV – age-quartile mean PWV)/ age-quartile SD of PWV). Results: PWV ranged from 4.1 to 15.0 m/s and correlated with age (r = 0.81, p < 0.0001), as expected. PWV average values (mean, SD) were for age quartiles: Q1: 6.0 ± 1.6; Q2: 6.7 ± 0.7; Q3: 7.9 ± 0.7; and Q4: 9.8 ± 1.5 m/s. A consumption of fruit greater than 7 servings/week (beta-coefficient -0.118 ± 0.061, p < 0.05) and physical activity (day per week) (beta-coefficient -0.032 ± 0.013, p < 0.01) were independent and significant determinants of the PWV z-score treated as a continuous variable, after controlling for age, sex and risk factors. When the likelihood of having a PWV z-score above the median (indicating EVA) was modelled, fruit consumption lost significance (odds ratio (OR) 0.99, 95% CI: 0.65–1.50). However, physical activity (OR 0.91, 95% CI: 0.83–0.99, p < 0.05) and a daily intake of seeds (OR 0.63, 95% CI: 0.41–0.96, p < 0.01) were still associated with reduced risk of EVA. This corresponded to the equivalent of having a 4 to10 year younger arterial system in subjects reporting healthy lifestyle. Conclusions: A healthy lifestyle was associated with lower risk of age- and risk factor adjusted PWV (arterial stiffness) as the core component of EVA in a diverse population from across Latin America.

[PP.21.11] REFERENCE VALUES AND DISTRIBUTION OF THE NEUTROPHIL TO LYMPHOCYTE RATIO IN A LARGE-SCALE POPULATION

Objective: During the last years, the Neutrophil to Lymphocyte Ratio (NLR) as a biomarker of inflammation has spread out its clinical application. Recent publications have confirmed its strong and positive predictive value for poor prognosis in diabetes and cardiovascular disease, and the development of hypertension. However, evidence is scarce regarding the average NLR and its distribution in the general population. Our aim was to describe the distribution of the NLR in a large-scale population classified by age and gender. Design and method: We analyzed data from consecutive non-hospitalized subjects over 16 years-old. Blood samples were drawn as part of general medical check-ups in 22 centers during 3 months of 2015, and analyzed in one central lab in 3 hematology analyzers (LH 750, Beckman Coulter). Internal quality controls of third opinion (Bio Rad) were used and subsequent monthly verification procedures of analytical bias were performed. NLR was calculated by dividing the number of neutrophils by number of lymphocytes. Then, NLR was classified and evaluated by gender and decades of life. Results: We included 71,873 subjects (ranged from 16 to 103 years, 66,1% female). Males had a NLR median between 1.50 (16 to 19years group) and 2.52 (>90 years group), with a gradual and constant increase between both ends. Women had a NLR median between 1.54 (16 to 19 years group) and 2.38 (>90 years group), with a first peak of NLR in the 30 to 49 years group (p < 0.001 compared with men at same age), and then a progressive increase similar to men. Conclusions: To the extent of our knowledge this is the first time that NLR distribution is explored in a large-scale population by gender and age. A direct and positive association was observed across lifespan in both genders. We hypothesized that an immuno-inflammatory component accompanying arterial aging and atherosclerosis may be the responsible physiopathology. The increase of NLR in the fertile stage of women deserves further research.