Exercise blood pressure response is related to asymmetric dimethylarginine and osteoprotegerin in hypertension

Abstract

Emerging evidence suggests that emphasis should be shifted from the diagnostic to the prognostic perspective of treadmill exercise testing [1–5]. There is also a close association of a hypertensive response to exercise with endothelial dysfunction [6], accelerated carotid atherosclerosis [7], and left ventricular hypertrophy [8]. Focusing, on asymmetric dimethylarginine (ADMA) it has considerable cardiovascular effects mainly by modulating arterial resistance and structure in renal and systemic circulation [9–11] and its levels are increased in essential hypertension [12,13].Ontheotherhand,osteoprotegerin (OPG)represents a link between bone and vascular metabolism [14–16]. The aim of the present study was to explore the possible associations of a hypertensive response to exercise with ADMA and OPG levels in hypertension. The study population consisted of 420 non-diabetic consecutive males (all Caucasian) with untreated and uncomplicated stage I-II essential hypertension that were eligible for exercise treadmill testing [17]. Diagnosis of hypertension and ruling out of secondary forms of hypertensionwasdoneaccording to guidelines [18,19]. Exclusion criteria included atherosclerotic cardiovascular disease, valvular heart disease, fasting glucose N125 mg/dl, augmented serum creatinine concentration or overt proteinuria at the dipstick test and any other clinically significant systemic disease. We also excluded subjects with left bundle brunchblock, preexcitation syndromes, pacing rhythm, atrialfibrillation and signs of left ventricular hypertrophy or ischemic disease. Based on the exclusion criteria 304 essential hypertensives were selected. Office blood pressure measurement was performed according to guidelines [18,19] and ambulatory blood pressure was recorded as has been described in detail [20]. Study participants performed symptomlimited exercise testing according to the multistage Bruce protocol on a Quinton 5000 treadmill system (Quinton Instruments, Seattle, WA, USA) [21]. The highest systolic blood pressure value achieved during the exercise stress test was the peak exercise systolic blood pressure and accordingly a hypertensive response to exercise was defined as a peak exercise systolic blood pressure ≥210 mmHg, in line with the Framingham criteria [22] while reasons for exercise test termination have been previously described [23]. Significant differences were determined using the Student independent-samples t test or the chi-square test where appropriate. Correlation analyses were performed using the Pearson's correlation coefficient andmultiple regressionwas used to examine the independent predictors of peak systolic blood pressure. Statistical significance was set at pb0.05. From the initial population, 54 patients were excluded due to an ischemic response at the electrocardiogram or failure to achieve the age-predicted target heart rate, leaving a total of 250 subjects eligible for final analysis. Hypertensive patients with a hypertensive response to exercise were older, had higher body mass index, waist circumference, office and 24-h systolic blood pressure (Table 1), while exhibited greater ADMA and OPG levels (Table 2 and Fig. 1 upper and lower panel). Accounting for confounders, including age, body mass index, waist circumference, smoking status, office systolic/diastolic blood pressure, glucose and lipid levels did not abolish the significant difference in log ADMA and log OPG (pb0.05). The hypertensive response group exhibited lower peak exercise heart rate, attenuated total exercise time and more impaired exercise capacity (Table 3).