Strategies for improvement of awareness, treatment and control of hypertension: results of a panel discussion.

High blood pressure (BP) is a major risk factor for coronary heart disease, heart failure, stroke, chronic kidney disease, end stage renal disease, and a variety of other clinically important outcomes. Results from the surveys described in this issue and elsewhere underscore a common finding that hypertension is both highly prevalent and insufficiently treated and controlled. Recognizing the differences in sampling and survey measurement techniques, the reported prevalence of hypertension (SBP/DBP >/=140/90 mmHg or treatment with antihypertensive medication) in adults exceeded 25% in all of the surveys reported in this issue. In Latvia, the prevalence of hypertension for 25-64-year-old adults in the general population was 46.1%. Control of hypertension with medication to an SBP/DBP <140/90 mmHg in the general population ranged from as low as 12% to a high of only 29%. Data from other parts of the world provide an equally distressing picture of what is (not) being accomplished in treatment and control of hypertension at the level of the general population. These data provide testimony to an urgent need for greater attention to the treatment and control of hypertension in populations around the world. This was the basis for a panel discussion at the International Society of Hypertension satellite conference The Epidemiology of Hypertension-Regional Differences in Treatment and Control. Panel participants included Drs P Whelton, S Sonkodi, DG Beevers, JG Fodor, H Elliot, R Cifkova, A Nissinen, A Javor, and there was active participation of other symposium attendees. The following summarizes key elements of the discussion and recommendations of the panel.

Hypertension screening in a salami factory: a worksite hypertension study.

The prevalence, awareness and control of hypertension are important epidemiological research topics worldwide. The screening of hypertension in a workplace has some special aspects. We have screened the employees in a Hungarian salami factory (Pick Salami Factory, Szeged, Hungary) for hypertensives. In a cross-sectional survey, the blood pressure (BP) was measured with an instrument meeting accepted measuring principles (BP-TRU BP) and a questionnaire was filled. In all, 1012 factory workers were screened (600 male and 412 female) and 25.7% of the workers proved to be hypertensives. Of these, 61.5% of the hypertensive employees were aware that their BP is high. Among the treated hypertensives, 21.9% were controlled. These results suggest that the efficacy of the management of hypertension in Hungary cannot be solely responsible for the high cardiovascular morbidity and mortality. The improvement of the management of hypertension should decrease the cardiovascular risk in the hypertensive population. The worksite screening and follow-up of hypertension seem to be logical health service solutions. This has been proven to be cost-effective.

Work-site hypertension prevalence and control in three Central European Countries.

Compared to Austria, cerebrovascular stroke (CVS) mortality is three times higher in Hungary, and twice as high in Slovakia. We hypothesized that this is due to better treatment and control of hypertension in Austria. To test this hypothesis, we carried out a cross-sectional survey of 'blue collar' employees on work sites in each of these countries. Blood pressure screening was carried out at three work sites in Austria, one in Hungary and one in Slovakia. A standardized protocol was followed in each of these countries. The Bp-TRU(TM) measuring instrument was used to provide accurate reproducible readings and eliminate interobserver error. After the exclusion of missing data and women, the study population included 323 males screened in Austria, 600 in Hungary, and 751 in Slovakia. The mean ages of the respondents ranged from 35 to 42 years. The prevalence of hypertension was 29% in Austria, 28% in Hungary and 40% in Slovakia. Of those identified as hypertensive, 73% in Austria, 45% in Hungary and 67% in Slovakia were newly diagnosed as a result of this screening. Of those treated for hypertension, 10% in Austria, 15% in Hungary and 5% in Slovakia were controlled. The differences in CVS mortality cannot be explained by better control of hypertension in Austria but indicate the involvement of other determinants.

A candesartan cilexetil/hydrochlorothiazide combination tablet provides effective blood pressure control in hypertensive patients inadequately controlled on monotherapy.

In this double-blind, placebo-controlled, randomised, parallel-group study, a combination tablet of candesartan cilexetil/hydrochlorothiazide (HCTZ), 16/12.5 mg once daily, reduced sitting diastolic blood pressure (DBP) significantly more (p = 0.037) than candesartan cilexetil/placebo, 16 mg once daily, in patients with mild to moderate primary hypertension (n = 328) who had not reached target blood pressure with candesartan cilexetil, 16 mg once daily. At the end of the 8-week double-blind treatment period, the adjusted mean reductions in sitting DBP, 24 h post dose, were 7.5 mm Hg in the candesartan cilexetil/HCTZ treatment group and 5.5 mm Hg in the candesartan cilexetil/placebo treatment group, corresponding to an adjusted mean difference between treatments of 2.0 mm Hg in favour of candesartan cilexetil/HCTZ (95% CI 0.1-3.8 mm Hg, p = 0.037). The adjusted mean reductions in sitting systolic blood pressure, 24 h post dose, were 12.0 mm Hg and 7.5 mm Hg, respectively, corresponding to an adjusted mean difference between treatments of 4.5 mm Hg (95% CI 1.1-8.0, p = 0.01). Consistent with the placebo-like tolerability of candesartan cilexetil reported in other studies, both treatments were very well tolerated, with a similar pattern and low frequency of adverse events in both treatment groups.

[Treatment of renal artery stenoses with stent implantation]. / Arteria renalis-szúkületek kezelése stentimplantatióval.

The authors report on their experience with the treatment of renovascular hypertension by stent implantation. In the past 4 years different types of stents (Palmaz [9], Palmaz-Corinthian [4], Memotherm [1] and AVE [1]) were implanted into 15 renal arteries of 11 patients. The indication was primary in 8 cases, and secondary in 3 patients, because of restenosis of a previously dilated renal artery. 14 stents were implanted into narrowed renal arteries, and in the remaining one case a stent was placed in an occluded renal artery immediately after recanalization. The technical success was 100%. In all but the recanalized case in which the renal artery was occluded, stents are still open. On the basis of this experience and the literature, the authors suggest the more extensive usage of this less invasive method.

AT1 receptor antagonists: a challenge for ACE inhibitors in diabetic nephropathy.

Due to its hemodynamic, metabolic and growth promoting effects, angiotensin II (AII) may play an important role in the pathogenesis of diabetic kidney disease. Consequently, decreasing the production or cellular action of AII is a rational target for therapeutic attempts aimed at slowing the progression of diabetic nephropathy. Based on their superior renoprotective performance in recent landmark studies, currently ACE inhibitors are the drugs of choice in diabetic patients with microalbuminuria or overt proteinuria. A new class of antihypertensive medications, the AT1 receptor antagonists may represent an alternative to ACE inhibitors in the treatment of diabetic nephropathy. They provide a more complete blockade of the renal renin-angiotensin system and are generally better tolerated than ACE inhibitors. On the other hand, AT1 receptor antagonists do not increase bradykinin levels, an effect that may contribute to the high level of renoprotection achieved by ACE inhibitors. Although human data are not available at this point, ACE inhibitors and AT1 receptor antagonists have similar beneficial effects on proteinuria, renal hypertrophy and glomerulosclerosis in animal models of diabetic kidney disease. Currently several prospective studies are being conducted to compare the efficacy of ACE inhibitors and AT1 receptor antagonists in the treatment of human diabetic nephropathy.

Hyposthenuria: Sándor Korányi's concept of renal insufficiency.

Around the turn of the 19th century, the Hungarian physiologist and clinician, Sándor Korányi, started to use physicochemical methods to estimate renal function. In parallel with the deterioration of renal function, he found characteristic changes in the freezing point depression of urine, which he termed hyposthenuria. On the basis of these findings, he was the first to introduce the functional concept of renal insufficiency.

[Thin glomerular membrane nephropathy. Clinico-pathological observations]. / A vékony glomerularis basalmembran nephropathia. Klinikopatológiai megfigyelések.

In two nephrology centres between 1983 and 1993 among 1545 kidney biopsies 34 cases of thin basement membrane nephropathy have been diagnosed. All patients had a varying degree of microscopic dysmorph haematuria, occasional slight proteinuria--except two nephrotic children; and normal blood pressure with one exception. 5 children and 7 adults experienced repeated bouts of macroscopic haematuria mainly after exercise or upper respiratory tract infection, one child after tonsillectomy. All patients had normal renal function and retained it during the follow-up period (mean 61 months, 3 months to 22 years), except a 46 year old patient, who was found to have the joint occurrence of light chain gammopathy and hypertension. Seven patients had positive family history for microscopic haematuria, in four family members of three patients renal biopsy disclosed mesangioproliferative glomerulonephritis with thin GBM segments. As a cut off value for thin basement membrane nephropathy we considered 264 nm. The morphometric analysis of the electron micrographs revealed a mean thickness of 210 nm. No differences in basement membrane thickness were measured regarding gender, age or the presence of macroscopic haematuria. The thin basement membrane is considered to be the pathological basis and predisposing alteration leading to haematuria.

Mitochondrial mutation as a probable causative factor in familial progressive tubulointerstitial nephritis.

Renal biopsy of two children and a maternal relative, diagnosed with severe progressive tubulointerstitial nephritis, has shown the presence of distorted mitochondria. Mitochondrial DNA from the blood of these patients was analysed. No major deletions were found, but an A to G mutation was detected in position 5656. It is proposed that this mutation might play a causative role in the renal disease of the patients.

Changes in left ventricular mass during treatment with minoxidil and cilazapril in hypertensive patients with left ventricular hypertrophy.

Attainment of the regression of hypertension-associated left ventricular hypertrophy (LVH) seems to be a desirable goal of blood pressure (BP)-reducing therapy. Since antihypertensive drugs of differing types may exhibit markedly different abilities to modulate LVH, we examined the effects of the angiotensin-converting enzyme inhibitor cilazapril, and the potassium channel activator minoxidil, alone or in combination with each other, on the left ventricular mass (LVM) in patients with severe essential hypertension who had LVH detected by echocardiography. All patients received the same base therapy of bopindolol and guanfacine. After a run-in period, they were treated with: (1) cilazapril (n = 10); (2) minoxidil, combined with a diuretic (n = 10); or (3) both cilazapril and monoxidil (n = 6) for 12 months. The LVM index (LVMI; LVM per body surface area) was estimated every 3 months by means of echocardiography. Each kind of therapy decreased the arterial pressures to a similar degree. The 1-year treatment with the cilazapril-based regimen resulted in a significantly diminished LVMI (from a mean +/- s.d. of 173 +/- 38 to 152 +/- 22 g/m2; P < 0.05). On the other hand, the minoxidil-based therapy led to a significant increase in LVMI (from 148 +/- 19 to 170 +/- 35 g/m2; P < 0.05). There were no significant LVMI changes in patients receiving the combined, cilazapril + minoxidil-based treatment (172 +/- 34 vs the pretreatment 183 +/- 54 g/m2). The results confirm that long-term treatment with cilazapril is effective both in reducing BP and in reducing LVM. In spite of yielding a satisfactory reduction of BP, minoxidil therapy, even in combination with a diuretic and a beta-blocker, may lead to an aggravation of pre-existing LVH; this effect of minoxidil could be prevented by the simultaneous administration of cilazapril.

Richard Bright in Hungary: a reevaluation.

Richard Bright, the highly respected physician and nephrologist at Guy's Hospital, had a strong liking for travel. In 1815 he traveled in Hungary and made very important observations about the country. His 762-page book, entitled Travels from Vienna through Lower Hungary has detailed, sometimes appreciative, sometimes very critical remarks and comments on Hungarian history, art, archeology, religion, the situation of nationalities, education, social conditions, law, farming, and mining. The Hungarians cherished the memory of Bright's travel in their country as reflected in several papers and on two commemorative tablets recognizing him as a true and sincere friend of Hungary.

Platelet eicosanoids and the effect of captopril in blood pressure regulation.

We investigated the eicosanoid synthesis of platelets of Wistar and of Okamoto spontaneously hypertensive rats (SHR), and the effect of captopril in vitro, using [14C]arachidonic acid as a tracer substrate and chromatographic determination. Lipoxygenase activity was elevated, while the formation of cyclooxygenase products was reduced in SHR platelets, compared to those of Wistar rats. This difference might play a role in the pathomechanism of hypertension in SHR. In SHR with lower blood pressure, captopril reduced thromboxane synthesis, while in SHR with higher blood pressure thromboxane synthesis was unchanged, but the synthesis of prostaglandin D2, a potent vasodilator, and of 12-L-hydroxy-5,8,10-heptadecatrienoic acid, a stimulator of endothelial prostacyclin formation, was increased. We may conclude that, in spite of the missing angiotensin converting enzyme in platelets, a direct effect on platelet eicosanoid synthesis could contribute to the blood pressure decreasing effect of captopril.

Quantitative ultrastructural study of afferent and efferent arterioles in IgA glomerulonephritis and benign nephrosclerosis.

Arteriolosclerosis frequently occurs in IgA nephritis (IgAN), and it is the hallmark of benign nephrosclerosis (BNS). The quantitative ultrastructure of juxtaglomerular arterioles is not known in these disorders. We examined afferent and efferent arterioles in renal biopsies from 25 adult patients with IgAN (hypertension at biopsy: 14 patients) and 9 patients with BNS. Six age-matched living renal transplant donors acted as controls. A systematic independent sample of profiles was obtained in thin sections taken at predetermined levels. The thickness of the media (myomedial cells plus the matrix) and the thickness of the medial matrix were estimated stereologically. From these estimates, the matrix/myomedia ratio was calculated. In IgAN with normotension or hypertension, the afferent media and its compartments did not exhibit significant thickening compared with the controls, whereas in BNS the afferent media and its layers were markedly and significantly thickened. The efferent media in IgAN and BNS displayed mild and significant thickening, with significant thickening of the matrix in BNS and IgAN with normotension. The matrix/myomedia ratio was not altered significantly in any group. The results indicate that the afferent arterioles are not the main sites of IgAN-related arteriolosclerosis, that arteriolosclerosis in IgAN and arteriolosclerosis in BNS are different lesions, and that increased efferent arteriolar thickness, demonstrated here for the first time in IgAN and BNS, might be a manifestation of angiotensin II-mediated autoregulatory efferent vasoconstriction exerted to maintain the glomerular filtration pressure.

[Effect of cilazapril in patients with essential hypertension: effect on cardiac hypertrophy]. / Cilazapril hatása essentialis hypertensiós betegekben: szívizom hypertrophiát befolyásoló hatás.

Numerous antihypertensive drugs exist with different modes of action, which have a really effective impact on hypertension. The life expectancy of hypertensive patients is known to depend on the degree of damage caused to their target organs by the hypertension itself. Cardiovascular hypertrophy and its complications are considered to be among the major elements of this process. This work evaluates the effectiveness of the long-term treatment of essential hypertensive subjects (n = 10) with a long-acting ACE-inhibitor, cilazapril, as concerns their blood pressure and cardiac hypertrophy. Cilazapril given orally in a daily dose of 2.5 mg effectively lowered both the systolic (delta 30 mm Hg) and the diastolic (delta 19 mm Hg) blood pressure. No changes were found in body weight or heart rate, and only one side-effects (skin rash) was reported. Cilazapril considerably decreased the left ventricular mass and hence the hypertrophic index of hypertensive patients with cardiac hypertrophy, suggesting that ACE inhibitors are effective not only in lowering blood pressure and decreasing hypertrophy, but also in lowering the cardiac morbidity and mortality.