Antonios Lazaridis

Renal Nerve Ablation for Resistant Hypertension: The Dust Has Not Yet Settled

Resistant hypertension represents a major clinical problem in everyday clinical practice, not only for hypertension experts but for nephrologists, cardiologists, internists, and primary care physicians alike. Resistant hypertension is frequently encountered among hypertensive patients, with a reported prevalence of approximately 10%. Resistant hypertension is considered a condition of high cardiovascular risk. Indeed, two recent studies found that resistant hypertension was associated with a 2.2-fold increased risk for cardiovascular morbidity and a 50% higher risk for cardiovascular events. The management of resistant hypertension is challenging and requires experience and expertise. A stepby-step approach should be implemented, excluding all potential causes of “pseudo-resistance”:

Management of erectile dysfunction in hypertension: Tips and tricks.

Arterial hypertension is a major risk factor for cardiovascular disease and affects approximately one third of the adult population worldwide. The vascular origin of erectile dysfunction is now widely accepted in the vast majority of cases. Erectile dysfunction is frequently encountered in patients with arterial hypertension and greatly affects their quality of life of hypertensive patients and their sexual partners. Therefore, the management of erectile dysfunction in hypertensive patients is of paramount importance. Unfortunately, erectile dysfunction remains under-reported, under-recognized, and under-treated in hypertensive patients, mainly due to the lack of familiarity with this clinical entity by treating physicians. This review aims to discuss the more frequent problems in the management of hypertensive patients with erectile dysfunction and propose ways to overcome these problems in everyday clinical practice.

PDE-5 inhibitors: clinical points.

Erectile dysfunction is usually of vascular origin and is frequently encountered in men with cardiovascular disease. The introduction of phosphodiesterase-5 inhibitors has revolutionized the management of patients with erectile dysfunction. Currently available phosphodiesterase-5 inhibitors have distinct pharmacokinetic and pharmacodynamic properties, thus permitting for tailoring sexual therapy according to patient characteristics and needs. Phosphodiesterase-5 inhibitors possess vasorelaxing properties and exert systemic hemodynamic effects, which need to be taken into account when other cardiovascular drugs are co-administered. Special caution is needed with alpha-blockers, while the co-administration with nitrates is contra-indicated due to the risk of life-threatening hypotension. This review presents the advent of sexual therapy, describes the mechanism of action and the specific characteristics of commercially available phosphodiesterase-5 inhibitors, summarizes the efficacy and safety of these drugs with special emphasis on the cardiovascular system, and discusses the clinical criteria used for the selection of each drug for the individual patient.

Combined angiotensin inhibition in diabetic nephropathy.

To the Editor: The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) study reported by Fried et al. (Nov. 14 issue)1 showed that dual blockade of the renin–angiotensin–aldosterone system confers a high risk of adverse effects among patients with diabetic nephropathy. Inhibitors of the renin–angiotensin–aldosterone system have been used successfully for slowing progression of diabetic nephropathy, but increasing the dosage to achieve better outcomes with a low risk of adverse effects remains controversial.2,3 As in previous clinical trials, Fried et al. have shown that combining an angiotensin II–receptor blocker (ARB) and an angiotensin-converting–enzyme (ACE) inhibitor or a direct renin inhibitor did not result in a benefit but was associated with an increased risk of adverse events.1,3,4 In our recent study, the combination of equipotent half doses of an ACE inhibitor (lisinopril) and an ARB (irbesartan), as compared with each single agent at higher doses, did not show any benefit with respect to the risk of progression; however, the incidence of adverse effects was similar in the two groups.5 We do not support the use of dual blockade, even if it is used in equipotent doses, because of the lack of benefit and the risk of complications.To the Editor: The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) study reported by Fried et al. (Nov. 14 issue)1 showed that dual blockade of the renin–angiotensin–aldosterone system confers a high risk of adverse effects among patients with diabetic nephropathy. Inhibitors of the renin–angiotensin–aldosterone system have been used successfully for slowing progression of diabetic nephropathy, but increasing the dosage to achieve better outcomes with a low risk of adverse effects remains controversial.2,3 As in previous clinical trials, Fried et al. have shown that combining an angiotensin II–receptor blocker (ARB) and an angiotensin-converting–enzyme (ACE) inhibitor or a direct renin inhibitor did not result in a benefit but was associated with an increased risk of adverse events.1,3,4 In our recent study, the combination of equipotent half doses of an ACE inhibitor (lisinopril) and an ARB (irbesartan), as compared with each single agent at higher doses, did not show any benefit with respect to the risk of progression; however, the incidence of adverse effects was similar in the two groups.5 We do not support the use of dual blockade, even if it is used in equipotent doses, because of the lack of benefit and the risk of complications.

A comparison study of brachial blood pressure recorded with Spacelabs 90217A and Mobil-O-Graph NG devices under static and ambulatory conditions

Ambulatory blood pressure monitoring is an important tool in hypertension diagnosis and management. Although several ambulatory devices exist, comparative studies are scarce. This study aimed to compare for the first time brachial blood pressure levels of Spacelabs 90217A and Mobil-O-Graph NG, under static and ambulatory conditions. We examined 40 healthy individuals under static (study A) and ambulatory (study B) conditions. In study A, participants were randomized into two groups that included blood pressure measurements with mercury sphygmomanometer, Spacelabs and Mobil-O-Graph devices with reverse order of recordings. In study B, simultaneous 6-h recordings with both devices were performed with participants randomized in two sequences of device positioning with arm reversal at 3 h. Finally, all the participants filled in a questionnaire rating their overall preference for a device. In study A, brachial systolic blood pressure (117.2±10.3 vs 117.1±9.8 mm Hg, P=0.943) and diastolic blood pressure (73.3±9.4 mm Hg vs 74.1±9.4 mm Hg, P=0.611) did not differ between Spacelabs and Mobil-O-Graph or vs sphygmomanometer (117.8±11.1 mm Hg, P=0.791 vs Spacelabs, P=0.753 vs Mobil-O-Graph). Similarly, no differences were found in ambulatory systolic blood pressure (117.9±11.4 vs 118.3±11.0 mm Hg, P=0.864), diastolic blood pressure (73.7±7.4 vs 74.7±8.0 mm Hg, P=0.571), mean blood pressure and heart rate between Spacelabs and Mobil-O-Graph. Correlation analyses and Bland–Altman plots showed agreement between the monitors. Overall, the participants showed a preference for the Mobil-O-Graph. Spacelabs 90217A and Mobil-O-Graph NG provide practically identical measurements during the static and ambulatory conditions in healthy individuals and can be rather used interchangeably in clinical practice.

Blood pressure variability is increasing from the first to the second day of the interdialytic interval in hemodialysis patients

Objectives: Patients with end-stage renal-disease under hemodialysis have increased cardiovascular risk and experience severe blood pressure (BP) fluctuations during the dialysis session and the subsequent interdialytic period. BP variability (BPV) may be an additional risk factor for cardiovascular events and preliminary data suggest increased BPV with advancing stages of chronic kidney disease. This is the first study to examine BPV during the whole intradialytic and interdialytic period in hemodialysis patients with ambulatory BP monitoring. Methods: A total of 160 patients receiving maintenance hemodialysis had 48-h ambulatory BP monitoring with the Mobil-O-Graph device during a regular dialysis session and the subsequent interdialytic interval. Brachial and aortic BPV were calculated with validated formulas and were compared between Days 1 and 2 of the interdialytic period (44-h), Days 1 and 2 of the total 48-h interval (including the dialysis session), and between the two respective daytime periods and night-time periods. Results: All brachial SBPV indices [SD: 14.75 ± 4.38 vs. 15.91 ± 4.41, P = 0.001; weighted SD: 13.80 ± 4.00 vs. 14.89 ± 3.90, P < 0.001; coefficient of variation (CV): 11.34 ± 2.91 vs. 11.93 ± 2.94, P = 0.011; average real variability (ARV): 11.38 ± 3.44 vs. 12.32 ± 3.65, P < 0.001)] were increasing from Days 1 to 2 of the 44-h interdialytic period. Similarly, all indexes of DBPV were significantly increased in Day 2, except for CV. Aortic SBPV and DBPV indices displayed a similar pattern. Furthermore, all studied brachial SBPV and DBPV indexes were also lower during daytimes 1 than 2 (systolic ARV 11.56 ± 3.98 vs. 12.44 ± 4.03, P = 0.002); systolic ARV was lower in night-time 1 compared with night-time 2 (11.20 ± 5.09 vs. 12.18 ± 4.66, P = 0.045). In multivariate regression analysis prehemodialysis SBP, age and diabetes were independently associated with increased SBP ARV. Conclusion: BPV is increased in interdialytic Day 2 compared with Day 1 in hemodialysis patients; this could be another mechanism involved in the complex cardiovascular pathophysiology and increased cardiovascular mortality of these individuals.

Diabetes Mellitus and Erectile Dysfunction

Diabetes mellitus, a contemporary growing pandemic, causes severe complications and provokes diminishing effects on the patient’s quality of life. Erectile dysfunction is one of the most common and earliest presented morbidity affecting diabetic men. Erectile dysfunction in diabetics is more severe and resistant to treatment, and its prevalence is two to three times higher than in nondiabetics. The etiology of this disorder induced by diabetes is multifactorial and complex. Ongoing research is focused on elucidating the physiology of the erectile mechanism and unraveling the mystery of the pathogenesis implicated in the development of erectile dysfunction. Endothelial dysfunction, autonomic and peripheral neuropathy, and endocrinological and psychological disorders are involved in the pathogenesis of diabetes-induced erectile dysfunction. The progress achieved in the comprehension of these mechanisms has led to the introduction of novel and promising molecule-based treatment options. Evidence suggests that combination therapy tailored to the individual is of high efficacy and results in the improvement of the sex-related daily life of men with diabetes.

Antihypertensive Therapy After Acute Ischemic Stroke

The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) study reported that antihypertensive therapy immediately after an acute ischemic stroke did not reduce the likelihood of death or major disability compared with placebo.1 In the trial, the effects of antihypertensive therapy seemed to be time dependent. Although the study revealed no effect of antihypertensive therapy when treatment was administered within the first day of stroke, blood pressure lowering was associated with a 27% reduction in the primary outcome among patients treated after 24 hours of stroke onset. This finding is in accordance with the results from the Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) study,2 in which candesartan was administered an average of 30 hours after recognition of stroke symptoms. Did Dr He and colleagues1 perform a formal interaction test3 to verify this finding? This finding comes from a subgroup analysis and can only be considered hypothesis generating, requiring further testing in future trials.

ASSOCIATION OF SERUM URIC ACID LEVELS WITH ARTERIAL STIFFNESS AND ENDOTHELIAL DYSFUNCTION IN A POPULATION OF NORMOTENSIVE TO EARLY-STAGE HYPERTENSIVE INDIVIDUALS

Objective: Objective: Hyperuricemia appears to be associated with increased cardiovascular risk. Both accelerated vascular stiffness and endothelial injury caused by increased oxidative stress have been postulated as contributing potential mechanisms. We investigated whether serum uric acid levels correlate with robust markers of arterial stiffness and endothelial dysfunction in a population of untreated individuals free from cardiovascular diseases, whose blood pressure ranged from normal to early-stage essential hypertension. Design and method: Design and Method: Individuals free from cardiovascular comorbidities, who received no medication for any reason, were eligible to participate. Arterial stiffness was estimated by the carotid-femoral pulse wave velocity (PWV) measurement with applanation tonometry using the Sphygmocor device. Serum samples were drawn for the measurement of uric acid levels and other biochemical parameters. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, was measured in serum samples using commercially available competitive enzyme-linked immunosorbent assay (ELISA) kit. Results: Results: A total of 241 individuals, 144 males and 97 females, with a mean age of 45.0 ± 11.2 years and mean systolic/diastolic blood pressure 138.8 ± 18.4/88.7 ± 12.0 mmHg, participated in the study. Mean PWV was 7.9 ± 1.8 m/s, while serum uric acid and ADMA levels were 5.1 ± 1.4 mg/dl and 1.00 ± 0.39 &mgr;mol/l, respectively. Uric acid positively correlated with both PWV (r = 0.152, p = 0.025) and ADMA levels (r = 0.141, p = 0.029). After adjustment for other variables (age, gender, body mass index, HDL cholesterol, triglycerides, glomerular filtration rate) in the multivariate analysis for uric acid, an independent association between with ADMA levels was observed (beta = 0.200, p < 0001), whereas the association between uric acid and PWV was no longer significant. Conclusions: Conclusion: In a population of untreated normotensive- to- early-stage hypertensive individuals, increased levels of uric acid are independently associated with endothelial dysfunction. On the other hand, the observed association between uric acid and arterial stiffness appears to be mediated by traditional cardiovascular risk factors. Uric acid might be implicated in the pathogenesis of cardiovascular diseases through endothelium-dependent mechanisms.

SYSTOLIC BLOOD PRESSURE PHENOTYPING BASED ON BOTH AORTIC AND BRACHIAL MEASUREMENTS AND ITS RELATIONSHIP WITH INTERMEDIATE HYPERTENSION PHENOTYPES AND ARTERIAL STIFFNESS

Objective: High aortic systolic blood pressure (aSBP) is stronger associated with target organ damage as compared to brachial systolic BP (bSBP). Office SBP phenotypes based on both brachial and aortic measurements have been recently proposed as a new classification system that could improve cardiovascular risk stratification and reveal subgroups of higher or lower risk of vascular damage. We sought to investigate: A) whether the above phenotyping could help to identify all hypertension phenotypes [True (TH), white-coat (WCH) and masked hypertensives (MH)] without applying ambulatory BP monitoring (ABPM), a gold standard method in the diagnosis of hypertension, however not always available in everyday clinical practice, and B) if the above combination of aSBP and bSBP is more sensitive to detect subgroups with increased arterial stiffness and thereby increased cardiovascular risk. Design and method: Based on their office bSBP and aSBP values, participants were classified into four office SBP phenotypes, using both the sex-adjusted 90th percentile and the rounded threshold of 130mmHg: type I was defined as both normal bSBP and aSBP, type II high bSBP with normal aSBP, type III normal bSBP but high aSBP and type IV both high bSBP and aSBP. Moreover, all participants underwent ABPM and were further classified into normotensives (NT), WCH, MH and TH. Arterial stiffness was assessed via pulse wave velocity (PWV). Results: The study included 391 untreated individuals (58.1% male) with a mean age of 44.0 ± 12.6 years (138 NT, 21 WCH, 52 MH and 180TH).No differences were observed in age, body mass index and smoking status. Most TH (68.9–87.8%) were type IV, while > 90% of normotensives were classified as type I. The majority of WCH (47.6–71.4%) were type IV, while < 45% of the MH had high aSBP and were type III. PWV was significantly lower between type I and all other types, as well as between III and IV type (p < 0.001). Conclusions: Our results showed that high aSBP deteriorates arterial stiffness regardless of the levels of bSBP. Therefore although SBP phenotyping doesn’t help to identify WCH or MH, its use in the everyday clinical practice can improve cardiovascular risk stratification.