A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product.

There is concern that testosterone replacement therapies might increase blood pressure (BP) with chronic use. Testosterone undecanoate is a novel oral testosterone therapy under development for the treatment of male hypogonadism. We studied the effects of testosterone undecanoate (225 mg twice daily) on ambulatory blood pressure (ABP) and heart rate, in 138 men with hypogonadism (mean age, 54 years, 79% white, 48% with a history of hypertension). Ambulatory BP and heart rate and hematologic parameters were obtained at baseline and following 4 months of daily therapy. Changes from baseline in ambulatory 24-hour, awake, and sleep systolic BP of 3.8 (p=0.06), 5.2 (p=0.01), and 4.3 mmHg (p=0.07) were observed post-treatment, respectively. Smaller changes in the diastolic BP were observed (1.2 (p=0.13), 1.7 (p=0.04), and 1.7 mmHg (p=0.11) for 24-hour, awake, and sleep, respectively). Changes in the 24-hour, awake and sleep heart rates were 1.9 (p=0.07), 2.6 (p=0.02), and 0.4 (p=0.68) beats/minute respectively. There were no significant differences in changes from baseline in the 24-hour ambulatory BP for the 57 subjects who had a medical history of hypertension versus the 61 subjects who did not have hypertension: 4.5/1.5 mmHg in the hypertension subgroup versus 3.2/0.9 mmHg in the non-hypertensive subgroup (p = 0.53/0.46 between groups). Hematocrit and hemoglobin increased by 3.2% and 0.9 g/dl in all subjects after 4 months of therapy. In those men in the top quartile of changes in hematocrit (corresponding to upper / lower boundary increases of 6 and 14% with 9.3% achieving levels > 52%), the largest increases in ambulatory systolic BP (8.3 mmHg) were observed, whereas the changes in ambulatory systolic BP in the lower 3 quartiles were substantially smaller (1.6, 3.2, and 2.7 mmHg in quartiles 1, 2 and 3 of hematocrit change, respectively). In conclusion, these data demonstrate increases in ambulatory BP occurred following 4 months of oral testosterone undecanoate, particularly in those men whose hematocrit rose by > 6% or whose resultant hematocrit was 52% or higher. Hence, hematocrit maybe a useful clinical parameter that could effectively predict the risk of developing increases in BP on oral testosterone undecanoate.

Ambulatory Blood Pressure Monitoring: Profiles in Chronic Kidney Disease Patients and Utility in Management.

Testosterone replacement therapies have been shown to increase blood pressure (BP) in hypogonadal men. We studied the effects of a new formulation of testosterone undecanoate (Kyzatrex™) on ambulatory blood pressure (ABP) and heart rate, in 155 men with hypogonadism (mean age, 50.5 years, 76.8% white, 36.1% on antihypertensive therapy). The ABP, heart rate and clinical assessments were obtained at baseline and following 120 and 180 days of therapy. Mean changes from baseline in 24‐h ambulatory systolic BP of 1.7 mmHg (95% CI, 0.3, 3.1) at day 120 and 1.8 mmHg (95% CI, 0.3, 3.2) at day 180 were observed post‐treatment. For those men on antihypertensive drug therapy, increases in mean 24‐h systolic BP were greater than those not taking antihypertensive drugs (3.4 vs 0.7 mmHg at day 120 and 3.1 vs 1.0 mmHg at day 180, respectively). Changes from baseline in 24‐h diastolic BP and heart rate at day 120 were smaller (<1 mmHg and <1 beat/min, respectively). There were no relationships observed between testosterone concentration or hemoglobin levels with ABP. Multivariable analyses showed that baseline ambulatory BP and antihypertensive therapy were significantly correlated with BP changes. These data demonstrate small increases in ambulatory BP following 120 days on this oral testosterone undecanoate with no further changes at 180 days. Changes in ambulatory BP were minimal in patients not taking antihypertensive therapy.

Context. High blood pressure (BP) is the most important risk factor for congestive heart failure (CHF) at a population level, but the relationship of an altered diurnal BP pattern to the risk of subsequent CHF is unknown. Objectives. To explore 24-hour ambulatory BP characteristics as predictors of CHF incidence and to investigate whether altered diurnal BP patterns confer any additional risk information beyond that provided by conventional office BP measurements. Design, Setting, and Participants. Prospective, community-based, observational cohort in Uppsala, Sweden, including 951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy at baseline between 1990 and 1995, followed until the end of 2002. Twenty-four-hour ambulatory BP monitoring was performed at baseline, and the BP variables were analyzed as predictors of subsequent CHF. The main outcome measure was first hospitalization for CHF. Results. Seventy men developed CHF during follow-up, with an incidence rate of 8.6 per 1000 person-years at risk. In multivariable Cox proportional hazards models adjusted for antihypertensive treatment and established risk factors for CHF (myocardial infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1-SD (9-mm Hg) increase in nighttime ambulatory diastolic BP (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.02–1.55) and the presence of “nondipping” BP (night-day ambulatory BP ratio ≥1; HR, 2.29; 95% CI, 1.16–4.52) were associated with an increased risk of CHF. After adjusting for office-measured systolic and diastolic Bps, nondipping BP remained a significant predictor of CHF (HR, 2.21; 95% CI, 1.12–4.36 vs normal night-day pattern). Nighttime ambulatory diastolic BP and nondipping BP were also significant predictors of CHF after exclusion of all participants who had an acute myocardial infarction before baseline or during follow-up. Conclusions. Nighttime BP appears to convey additional risk information about CHF beyond office-measured BP and other established risk factors for CHF. The clinical value of this association remains to be established in future studies.—Ingelsson E, Bjorklund-Bodegard K, Lind L, et al. Diurnal blood pressure pattern and risk of congestive heart failure. JAMA. 2006;295:2859–2866. Comment. Ambulatory BP monitoring provides information that is not obtained from conventional office-based BP measurement, such as mean BP over a 24-hour period and circadian BP patterns. Staessen et al1demonstrated that a nondipping pattern of BP (night-day ambulatory BP ratio ≥1) and nighttime BP more accurately predicted cardiovascular events than daytime BP. A reduced circadian BP variation is a common finding in CHF patients. The association of diastolic dysfunction with increased diastolic BP and nondipping in patients with hypertension and type 2 diabetes is also known. The primary aim of this study was to determine what characteristics of the 24-hour ambulatory BP measurements best predicted new-onset CHF, and how these characteristics of the 24-hour ambulatory BP measurements compared with office measurements. The prospective, community-based, observational cohort included 951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy at baseline followed for a median of 9.1 years. Twenty-four-hour ambulatory BP monitoring along with office-based BP measurements were performed at baseline, and the BP variables, including nondipping pattern, were analyzed as predictors of subsequent CHF. Seventy men developed CHF during follow-up, with an incidence rate of 8.6 per 1000 person-years at risk. After adjusting for antihypertensive treatment and established risk factors for CHF (myocardial infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1-SD (9-mm Hg) increase in nighttime ambulatory diastolic BP and the presence of nondipping BP were associated with an increased absolute risk of CHF. A 5-mm Hg increment in nighttime ambulatory diastolic BP was associated with a 13%–25% increased risk of CHF. After adjusting for office-measured systolic and diastolic Bps, nondipping pattern remained a significant predictor of CHF. The incidence of CHF was 15 cases higher per 1000 person-years at risk for those with nondipping vs normal night—day BP pattern. Nighttime ambulatory diastolic BP and nondipping BP were also significant predictors of CHF even after exclusion of all participants who had an acute myocardial infarction before baseline or during follow-up. The few limitations of this study include limited generalizability to women and other age or ethnic groups, inadvertent exclusion of nonhospitalized patients with mild CHF, and unknown impact of BP pattern on systolic vs diastolic HF. The pathophysiologic mechanism behind this association is not yet clear, but the authors speculate that endothelial dysfunction and/or increased sympathetic activity may be dysfunctions playing significant roles. Reversed circadian BP pattern (nondipping) may be important per se or may be an indicator of an important trait like sleep apnea. Previous studies have shown an association of nondipping nocturnal Bps and ambulatory BP readings with both cardiovascular disease incidence and left ventricular hypertrophy, and these findings with regard to CHF are consistent. The authors are rightfully cautious about the clinical implications of these findings, but they may provide additional clues to understanding the progression from hypertension to CHF.

A New Era of Renal Denervation Trials for Patients With Hypertension?

Cardiovascular Risk Associated With White-Coat Hypertension: Con Side of the Argument.

Introduction For practical reasons, blood pressure values measured by physicians or nurses in a medical environment remain the clinical basis of the diagnosis and management of arterial hypertension around the world as recommended by all guidelines [1–4]. Nevertheless, measurements of blood pressure outside the office have gained an increasing popularity over the last decades not only to ascertain the diagnosis of hypertension but also to follow the impact of therapeutic interventions. Out-of-office blood pressure measurements can be obtained either by 24-h ambulatory blood pressure monitoring or by home blood pressure monitoring. As reviewed recently [5], both sets of out-of-office blood pressure offer undeniable advantages when compared to office blood pressure. First, both ambulatory blood pressure and home blood pressure monitoring provide more reliable and reproducible information on blood pressure. Second, blood pressure values obtained by ambulatory blood pressure and home blood pressure monitoring appear to be more closely related to target organ damage than office blood pressure and hence have a greater prognostic relevance than office blood pressure. Third, certain diagnosis such as white coat hypertension and masked hypertension can only be diagnosed using out-of-office blood pressure measurements. Fourth, when used in the clinical follow-up of treated hypertensive patients to evaluate the impact of drug treatment, ambulatory blood pressure monitoring as well as home blood pressure monitoring has the advantage of not being affected by a placebo effect. Finally, evidence has been provided that treatmentinduced reduction in 24-h blood pressure may predict better than office blood pressure the regression of end organ damage (particularly the cardiac one) induced by antihypertensive drug. Many of these information have been achieved during the past two decades by a number of studies carried out in different populations around

Out-of-office blood pressure measurement in children and adolescents

Ambulatory Blood Pressure in Chronic Kidney Disease: Ready for Prime Time?

Effects of a Novel Oral Testosterone Undecanoate on Ambulatory Blood Pressure in Hypogonadal Men.

To the Editor: We read with interest the paper by Sega et al regarding the prognostic value of ambulatory, home, and office blood pressure in the PAMELA population.1 However, we find that the main conclusions of the report may be driven by the lack of adjustment for confounders. The relationships between level of blood pressure and risk were not adjusted for age, which may have a major influence on risk over a long time span. There is indeed a relation between age and blood pressure,2 and therefore, these results may be biased. The comparisons of the various blood pressures were also not adjusted for potential confounders, with the argument that “no adjustment for age, sex, and other cardiovascular risk factors was made because comparisons between the predictive value of various blood pressure values involved the same sample.” However, it has been shown in a general Belgian population that the within-subject differences between office and ambulatory blood pressure measurements increased with older age and greater body mass index.3 In addition, in the Danish MONICA population, the within-subject differences between office and ambulatory blood pressure measurements increased with older age, diagnosis of hypertension, male gender, and presence of diabetes.4 So, to assess the true prognostic value of office blood pressure versus that of ambulatory blood pressure, it is mandatory to explore whether adjustments for other relevant cardiovascular risk factors would change the results. Recently, it was shown in the Danish MONICA population that ambulatory blood pressure was a much better predictor of all-cause mortality and cardiovascular mortality than office blood pressure, taking other relevant risk factors into account.5 Accordingly, to make the results from previous studies comparable to the PAMELA study, we would like to know the results of adjusted analyses. Until that time, the conclusion that …

Relationship of Office and Ambulatory Blood Pressure With Left Ventricular Global Longitudinal Strain

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Out-of-Office Blood Pressure Monitoring: A Comparison of Ambulatory Blood Pressure Monitoring and Home (Self) Monitoring Of Blood Pressure.

UK Guidelines Call for Routine 24-Hour Ambulatory Blood Pressure Monitoring in All Patients to Make the Diagnosis of Hypertension-Not Ready for Prime Time in the United States