Stella Douma

Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study.

BACKGROUND Results of several studies published since 1999 suggest that primary hyperaldosteronism (also known as Conns syndrome) affects more than 10% of people with hypertension; however, such a high prevalence has also been disputed. Experts generally agree that resistant hypertension has the highest prevalence of primary hyperaldosteronism, on the basis of small studies. We aimed to assess the prevalence of primary hyperaldosteronism in a large group of patients with resistant hypertension. METHODS Patients with resistant hypertension (blood pressure >140/90 mm Hg despite a three drug regimen, including a diuretic) who attended our outpatient clinic were assessed for primary hyperaldosteronism. Serum aldosterone and plasma renin activity were determined and their ratio was calculated. Patients with a positive test (ratio >65.16 and aldosterone concentrations >416 pmol/L) underwent salt suppression tests with intravenous saline and fludrocortisone. Diagnosis of primary hyperaldosteronism was further confirmed by the response to treatment with spironolactone. FINDINGS Over 20 years, we studied 1616 patients with resistant hypertension. 338 patients (20.9%) had a ratio of more than 65.16 and aldosterone concentrations of more than 416 pmol/L. On the basis of salt suppression tests, 182 (11.3%) patients had primary hyperaldosteronism, and response to spironolactone treatment further confirmed this diagnosis. Hypokalaemia was seen only in 83 patients with primary hyperaldosteronism (45.6%). INTERPRETATION Although the prevalence of primary hyperaldosteronism in patients with resistant hypertension was high, it was substantially lower than previously reported. On the basis of this finding, we could assume that the prevalence of primary hyperaldosteronism in the general unselected hypertensive population is much lower than currently reported. Thus, the notion of an epidemic of primary hyperaldosteronism is not supported.

Female sexual dysfunction in essential hypertension: a common problem being uncovered.

Objectives Female sexual dysfunction (FSD) is increasingly attracting more scientific and public interest, and represents a poorly investigated issue in patients with essential hypertension. We evaluated the prevalence of sexual dysfunction in hypertensive women compared with normotensive women according to age, hypertension severity, hypertension duration, and antihypertensive treatment. Methods The study population consisted of consecutive, sexually active women attending an outpatient hypertension clinic. The Female Sexual Function Index (FSFI questionnaire) was used to evaluate FSD. Univariate and multivariate analyses were used to evaluate predictors of FSD. Results Four hundred and seventeen women were studied. From them, 216 women had arterial hypertension (136 treated, 80 untreated) and 201 were normotensive. Sexual dysfunction was found in 42.1% of hypertensive women compared with 19.4% of normotensive women (odds ratio, 3.2; 95% confidence interval, 1.9–4.7; P < 0.001). Systolic blood pressure levels were significantly related to FSFI score (r = −0.67, P < 0.001). Successful control of hypertension was related to lower prevalence of FSD. Increasing age (β = −0.187, P = 0.001), increasing systolic blood pressure (β = −0.687, P < 0.001), and β-blocker administration (β = −0.162, P = 0.001) were significant predictors of sexual dysfunction in this patient population. Conclusions FSD is more prevalent in women with essential hypertension compared with women with normal blood pressure, and its prevalence declines with adequate blood pressure control. Adequate control of hypertension with medication not affecting sexual function can have a great impact on the quality of life of hypertensive patients. Physicians should recognize and properly manage FSD in hypertensive women.

The effect of antihypertensive drugs on erectile function: a proposed management algorithm.

The pharmacologic management of hypertension has long been implicated in the genesis of erectile dysfunction; the latter is considered the main reason of nonadherence to antihypertensive therapy. Older‐generation antihypertensive drugs (central‐acting, β blockers, diuretics) negatively affect erectile function, while newer‐generation agents (calcium antagonists, angiotensin‐converting enzyme inhibitors) seem to have neutral effects. Preliminary data with the latest drugs (angiotensin receptor blockers) point to a beneficial effect on erectile function. Phosphodiesterase‐5 inhibitors, used for the treatment of erectile dysfunction, can be safely and effectively administered to hypertensive patients (even when on multiple‐agent antihypertensive therapy), with a caution regarding α blockers. In the case when erectile dysfunction is considered to result from antihypertensive therapy, the treating physician may either add phosphodiesterase‐5 inhibitors or substitute current treatment with angiotensin receptor blockers.

Reactivation of chronic hepatitis B virus infection following rituximab administration for rheumatoid arthritis

In chronic hepatitis B virus infection, immune suppression has been linked with potential activation and, in a number of cases, acute liver failure and fatal outcome; patients with haematologic or other malignancies under chemotherapy were mostly aVected [1]. In the same cohort of patients the incidence of HBV reactivation rose signiWcantly in the past decade, after the introduction of rituximab, a monoclonal antibody targeted against the CD20(+) lymphocytes [2, 3]. In this setting, reactivation was recorded even in HBsAb(+) patients [4]. In patients with rheumatic diseases, analogous cases are still mainly anecdotal. Taking into account the increasing application of rituximab in the treatment of autoimmune diseases, and the global prevalence of chronic hepatitis B virus infection, cases of treatment-induced reactivation need to be recorded, in order to formulate prophylaxis and treatment guidelines, and to safely establish the safety proWle of these agents in analogous circumstances [5].

Renal sympathetic denervation: the jury is still out.

The Symplicity HTN-2 Investigators deserve credit for building on the proof-of-principle study, and for addressing a substantial concern (the need for a randomised trial) by undertaking the fi rst RCT of renal sympathetic denervation in patients with treatmentresistant hypertension. Hypertension is the most common indication for lifelong treatment, mainly because of the incontrovertible reductions in cardiovascular events. Despite the abundance of antihypertensive drugs, control of blood pressure rates remains disappointingly low worldwide. Many patients who are uncontrolled present resistant hypertension (ie, uncontrolled blood pressure despite the use of optimum doses of three antihypertensive drugs, one being a diuretic). Although salt restriction and spironolactone treatment are eff ective for resistant hypertension, they have not gained Published Online November 17, 2010 DOI:10.1016/S01406736(10)62111-3

Angiotensin Converting Enzyme Gene Polymorphism is Not Related to Essential Hypertension in a Greek Population

Studies in various ethnic groups have shown contradictory evidence on the association of the angiotensin converting enzyme (ACE) insertion/ deletion (I/D) polymorphism with essential hypertension. In addition, mistyping of the insertion allele in heterozygotes has been reported. We analyzed the ACE genotype of 98 hypertensive and 84 normotensive subjects of Greek origin. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers were flanking the polymorphic region in intron 16 of the ACE gene. To avoid mistyping of heterozygotes, samples with the DD genotype were also amplified with primers that detect only the insertion allele. The distribution of the DD, ID, and II ACE genotypes was 30, 45, and 23 in hypertensive patients and 29, 40, and 15 in normotensive subjects, respectively. The estimated frequency of the insertion allele was 0.45 in hypertensive and 0.42 in normotensive subjects. The difference was not statistically significant. The results indicate a lack of association between ACE I/D polymorphism and essential hypertension in this Greek population, suggesting that other genes must contribute to the pathogenesis of hypertension.

Nitric oxide dysfunction in vascular endothelium and platelets: role in essential hypertension.

Both endothelial and platelet-derived nitric oxide have important vasculoprotective properties. Increasing evidence suggests a dysfunctional platelet nitric oxide synthase type 3 (NOS3) pathway in essential hypertension, whereas for endothelial-derived nitric oxide the picture is more complicated, with many studies suggesting an impairment of endothelial nitric oxide generation, whilst others have suggested that the endothelial nitric oxide pathway is preserved. Controversy also exists as to whether any observed reduction in endothelial or platelet-derived nitric oxide exerts a pathogenetic role or is simply the result of the raised blood pressure. In this review, we examine the evidence that endothelial and/or platelet-derived nitric oxide are disturbed in essential hypertension, and whether such disturbances are cause or effect.

Tumor necrosis factor-a antagonist-induced psoriasis: yet another paradox in medicine.

The therapeutic use of tumor necrosis factor a (TNFa) antagonists has added a highly effective treatment in the field of inflammatory musculoskeletal, skin, and bowel diseases. Most of the side effects of these very potential agents, like infections or skin reactions, were predictable; the development of psoriatic lesions was not, as they are very successfully used to treat psoriasis and psoriatic arthritis, too. There is a number of cases of anti-TNFa-induced psoriatic lesions in the literature, some of them developing with the use of two agents in the same patient, clearly suggesting a class effect. We report an additional series of 12 cases from a total of 300 patients (>800 patient years) and hypothesize on several mechanisms for the explanation of this paradoxical phenomenon namely, local action of TNF, dysregulation of regulatory T cells, or, finally, imbalance between TNF and interferon-a locally. Further studies are needed to elucidate the exact pathogenesis of these manifestations, so that the use of these agents will not only have changed the course of diseases like rheumatoid arthritis or ankylosing spondylitis but may also aid our in depth understanding of the underlying process of disease.

Platelet Activation in Essential Hypertension: Implications for Antiplatelet Treatment

Essential hypertension is associated with increased risk of arterial thrombotic disease. Among other factors, enhanced platelet activity contributes significantly to this phenomenon. An increased level of circulating monocyte-platelet aggregates (MPAs) represents one of the most robust markers of platelet activation; furthermore, these aggregates are also believed to contribute to the pathophysiology of atherothrombotic disease. Putative mechanisms that contribute to platelet activation in essential hypertension include endothelial dysfunction, neurohumoral (sympathetic and renin-angiotensin systems) overactivity, decreased platelet nitric oxide (NO) biosynthesis, and platelet degranulation secondary to increased shear. Current recommendations are that hypertensive patients receive aspirin therapy only if their calculated cardiovascular risk is high and their blood pressure (BP) is adequately controlled. By contrast, the use of antiplatelet treatment in low-risk hypertensive patients is not established and merits further investigation. Moreover, the place of alternative antiplatelet agents other than aspirin, such as clopidogrel, is unclear at present. Some experimental evidence suggests that clopidogrel may confer an additive protective effect over and above aspirin in hypertensive patients, by virtue of effects on the evolution of the atherosclerotic process. This now needs to be investigated in long-term clinical outcome studies.

The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease.

BackgroundAcute vigorous exercise, associated with increased release of plasma catecholamines, transiently increases the risk of primary cardiac arrest. We tested the effect of acute submaximal exercise on vasoactive substances and their combined result on platelet function.MethodsHealthy volunteers, hypertensive patients and patients with coronary artery disease (CAD) performed a modified treadmill exercise test. We determined plasma catecholamines, thromboxane A2, prostacyclin, endothelin-1 and platelet aggregation induced by adenosine diphosphate (ADP) and collagen at rest and during exercise.ResultsOur results during exercise showed a) platelet activation (increased thromboxane B2, TXB2), b) increased prostacyclin release from endothelium and c) decreased platelet aggregation in all groups, significantly more in healthy volunteers than in patients with CAD (with hypertensives lying in between these two groups).ConclusionDespite the pronounced activation of Sympathetic Nervous System (SNS) and increased TXB2 levels during acute exercise platelet aggregation decreases, possibly to counterbalance the prothrombotic state. Since this effect seems to be mediated by the normal endothelium (through prostacyclin and nitric oxide), in conditions characterized by endothelial dysfunction (hypertension, CAD) reduced platelet aggregation is attenuated, thus posing such patients in increased risk for thrombotic complications.