Malignant Phase Hypertension Research Articles

PS-BPR03-11: A CASE OF MALIGNANT PHASE HYPERTENSION ASSOCIATED WITH PRIMARY ALDOSTERONISM

Background: Primary aldosteronism is associated with low plasma renin levels, while malignant phase hypertension is generally associated with raised renin activity. Therefore, these two conditions are at opposite ends of the renin spectrum, so in theory their co-existence would be unusual. Case presentation: We present a case of a 41-year-old male with uncontrolled hypertension on multiple antihypertensive drugs. He discontinued these drugs for three days, thereafter he admitted to our hospital with congestive heart failure and acute ischemic stroke. He manifested malignant phase hypertension (blood pressure 216/130 mmHg; Keith-Wagener IV) accompanying renal dysfunction (serum creatinine 2.4 mg/dL), high plasma aldosterone concentration (PAC, 221 pg/mL) and mildly elevated plasma renin activity (PRA, 3.0 ng/mL/hr). A computed tomography did not reveal the presence of adrenal mass. After the treatment for congestive heart failure, the reassessment for endocrine causes of hypertension showed high level of PAC (468 pg/mL) and low level of PRA (0.2 ng/mL/hr), resulting in a high PAC/PRA ratio under the treatment with angiotensin-converting enzyme inhibitor. Adrenal venous sampling (AVS) confirmed the excessive aldosterone secretion from bilateral adrenal glands. Given these findings, we diagnosed him with idiopathic aldosteronism. After an addition of the mineralocorticoid receptor antagonist, he could keep his blood pressure under control. Conclusions: PRA in patients with primary aldosteronism could be increased under the conditions in which renin release from the kidney is overstimulated by glomerular ischemia, leading to an incorrect diagnosis of primary aldosteronism. Repeated endocrine assessment including the measurement of PRA and PAC should be considered to reveal the cause of malignant phase hypertension.

Elevated Plasma Renin Activity Caused by Accelerated-malignant Hypertension in a Patient with Aldosterone-producing Adenoma Complicated with Renal Insufficiency.

During the malignant phase of hypertension in patients with primary aldosteronism complicated with severe renal failure, the plasma renin activity may markedly increase with a false negative screening result for primary aldosteronism, thus potentially leading to a missed diagnosis of primary aldosteronism. We herein report the case of 37-year-old man who presented with accelerated-malignant hypertension complicated with severe renal insufficiency. The plasma renin activity was markedly increased in the malignant phase of hypertension, which were atypical results for primary aldosteronism. However, a plain abdominal computed tomography scan revealed a left adrenal nodule, which was diagnosed as aldosterone-producing adenoma by adrenal venous sampling.

Predictors of 5-year outcomes in malignant phase hypertension: the West Birmingham Malignant Hypertension Registry.

Malignant hypertension represents a high-risk condition and there are scarce data on current clinical patterns of this condition. The aim of the study is to identify the clinical and demographic factors associated with poor outcome. The data collected from 1958 to May 2016 included a total of 351 patients whose 5-year survival status was known: 221 white Caucasians (63%, age 51 ± 13 years, 64% male), 83 African-Caribbeans (24%, 45 ± 11 years, 61% male), and 47 South Asians (13%, 42 ± 11 years, 74% male). During the 5-year follow-up 119 (34%) patients suffered a primary outcome, defined as the composite endpoint of death or dialysis. The 5-year mortality ranged from 76% in patients diagnosed before 1967 to 7% in patients diagnosed between 1997 and 2006. The independent predictors of outcome were advanced age (vs. a reference group of < 40-year-old; P = 0.01 for age at presentation 51-60 years, P < 0.001 for age > 60 years), prior use of antihypertensive medications (P = 0.002), higher serum creatinine (P = 0.006), and proteinuria (P < 0.01). Also, white Caucasian (odds ratio12.02, 95% confidence interval 1.64-88.15, P = 0.01) and African-Caribbean (odds ratio 15.55, 95% confidence interval 2.06-117.29, P = 0.008) origins were associated with higher mortality vs. South Asians. The years of the diagnosis after 1977 were significantly associated with lower composite endpoint of death or dialysis, all P < 0.01. There has been a major improvement in 5-year survival in patients with malignant hypertension over recent decades. Abnormal renal function at presentation still predicts worse outcome. South Asian ethnicity is also associated with better outcome, although mechanisms involved are yet to be established.

Comparison of Renal Outcome among Japanese Patients with or without Microangiopathic Hemolysis in Malignant Phase Hypertension: A Single-Center Retrospective Study

Background/Aims: Although microangiopathic hemolysis (MAH) is a well-known complication of malignant phase hypertension (MPH), only less data on whether MAH in MPH predicts renal outcome exist. Therefore, we evaluated whether MAH was associated with the renal outcome in patients with MPH. Methods: We conducted a single-center, retrospective, cohort study. Data from 35 patients diagnosed with MPH between October 1998 and January 2015 were analyzed. MPH was defined as the presence of a diastolic blood pressure of ≥120 mm Hg and grades III/IV hypertensive retinopathy according to the Keith-Wagener-Barker classification. MAH was defined as the presence of a low platelet count (<150 × 10⁹/L) together with either an elevated level of lactate dehydrogenase (LDH; >220 U/L), or the presence of schistocytes, or both and the normalization of platelet and LDH level or schistocyte levels after adequate blood pressure control was achieved. The primary outcome was dialysis induction. Results: Fifteen patients had MAH. Those with MAH had significantly severe renal dysfunction at the onset of MPH. The length of follow-up (median, interquartile range) of patients with MAH and those without MAH were 30 (16-94) and 48 (25-115) months, respectively. Dialysis was induced in 9 of 15 patients with MAH and in 6 of 20 patients without MAH. Renal survival in patients with MAH was worse than that in those without, but this was not statistically significant (p = 0.08). By multivariate Cox regression analysis, MAH was not shown to contribute to dialysis induction. Conclusion: MAH did not predict renal outcome in MPH.

Malignant hypertension: new aspects of an old clinical entity

Malignant hypertension (MHT), also known as accelerated-malignant hypertension or malignant-phase hypertension, is the most severe form of arterial hypertension. It is defined clinically as high blood pressure (BP) levels associated with lesions of the retinal fundus (flame-shaped hemorrhages, exudates, or cotton wool spots, with or without papilledema). Despite the availability of a vast range of antihypertensive agents, MHT continues to be a significant clinical challenge. Although its prevalence is very low, the absolute number of new cases has not changed over the past decades. While the role of the activation of the renin-angiotensin-aldosterone system and endothelial dysfunction in the pathogenesis of MHT has been well described, recent studies have indicated that the immune system may also play an important role in the development of this condition. Patients with MHT are characterized by pronounced target organ damage, including structural and functional cardiac abnormalities. MHT is frequently complicated by renal insufficiency and end-stage renal disease. The survival rates for patients with MHT have improved considerably with increased availability of antihypertensive treatment. However, renal insufficiency and end-stage renal disease still remain a significant cause of morbidity and mortality in this patient group. In conclusion, MHT is not a "vanishing disease" because there is a relatively stable number of new cases per year. Nonetheless, prognosis and survival rates in these patients have improved significantly owing to earlier detection, stricter BP control, lower BP targets, better choice of antihypertensive drugs, and availability of hemodialysis and renal transplantation.

Successful Treatment with an Antihypertensive Drug Regimen Including Eplerenone in a Patient with Malignant Phase Hypertension with Renal Failure

A 28-year-old man was referred to our hospital for the treatment of congestive heart failure and severe hypertension. The patient was diagnosed with malignant phase hypertension based on the presence of marked hypertension with left ventricular hypertrophy, exudate retinopathy, and renal failure. Intensive therapy for hypertension and heart failure with a combination of antihypertensive drugs including nitroglycerin, nifedipine, eplerenone and candesartan successfully lowered his blood pressure and further improved the renal function. Eplerenone could be one of the choices of antihypertensive drugs in combination therapy in patients with malignant phase hypertension with progressive heart and renal failure.

Does obesity influence target organ damage and outcomes in patients with malignant phase hypertension? The West Birmingham Malignant Hypertension Project

Several studies have suggested that hypertension has a stronger detrimental impact on cardiovascular outcome in lean than in obese persons, but neutral or opposite results have also been reported. We investigated the impact of baseline body mass index (BMI) at presentation with the most severe form of hypertension, that is, malignant phase hypertension (MPH) on the primary outcome of 'death or dialysis' in these patients. A total of 184 patients (overall mean (s.d.) age 48 (13) years; 61% male; 62% White-European; 20% African-Caribbean, 18% South-Asian) from the West Birmingham MPH Register were included. The patients were grouped according to their BMI (underweight, normal weight, overweight and obese groups). Ninety-three primary outcomes occurred during a median (interquartile range) follow-up of 10.7 (5.8-18.6) years. No significant baseline differences in age or ethnicity were seen between the study groups. Overweight and obese patients included a larger proportion of females, but less smokers than those underweight or of normal weight. There was no inter-group difference in retinopathy (P=0.25), proteinuria (P=0.08), haematuria (P=0.56) and left ventricular hypertrophy (P=0.14). In univariate analyses, BMI was predictive of death or dialysis (0.95 (0.90-1.00), P=0.046) but multivariate analyses showed that only baseline age (odds ratio (95% confidence intervals) 1.06 (1.03-1.09), P<0.001), smoking (2.89 (1.40-5.92), P=0.004), creatinine level (1.01 (1.01-1.02), P=0.001) and estimated glomerular filtration rates (0.99 (0.93-1.00), P=0.047) were independently associated with death or dialysis. BMI was not an independent predictor of adverse outcomes in MPH patients. Age, smoking status, creatinine levels and estimated glomerular filtration rates at diagnosis of MPH were independent predictors for death or dialysis in this high-risk population of hypertensive patients.

Lack of impact of pulse pressure on outcomes in patients with malignant phase hypertension

To investigate the impact of pulse pressure at presentation on the primary outcome (death or dialysis) in patients with malignant phase hypertension (MPH). Three hundred and sixty-five patients [overall mean (SD) age 48 (13) years; 66% male; 63% white European; 23% African-Caribbean, 14% south Asian] from the West Birmingham MPH study were included. Baseline pulse pressure was divided into quartiles. Two hundred and forty-two primary outcomes (death or dialysis) occurred during a median (interquartile range) follow-up of 7 (1.5-14.8) years. Significantly higher pulse pressure was evident among older patients and white Europeans. Baseline BMI (P = 0.49), retinopathy (P = 0.56), proteinuria (P = 0.61), haematuria (P = 0.56) and left ventricular hypertrophy (P = 0.43) were not related to pulse pressure. Multivariate analyses found that baseline age [hazard ratio (95% confidence intervals] [1.05 (1.04-1.06); P < 0.0001], smoking [1.60 (1.16-2.21); P = 0.004], proteinuria [1.33 (1.10-1.61); P = 0.003] and creatinine level [1.002 (1.001-1.002); P < 0.0001] were independent predictors of the primary outcome of 'death or dialysis'. A multivariate analysis also revealed that independent predictors of future dialysis alone were as follows: baseline age [0.92 (0.89-0.95); P < 0.001) and haematuria [2.74 (1.17-6.42); P = 0.02), with a trend seen for baseline creatinine levels [1.001 (1.000-1.002); P = 0.052)]. Pulse pressure at baseline did not predict death or dialysis. Age, smoking status and severity of renal failure at presentation with MPH (represented by proteinuria and creatinine levels) are independent predictors of the risk of death or dialysis. Pulse pressure at presentation does not predict death or dialysis in patients with MPH. Careful monitoring of renal functioning and effective management of blood pressure is mandatory in patients with MPH to prevent/slow future complications.

Hypertensive crisis

Hypertensive crisis

A comprehensive assessment of cardiac structure and function in patients with treated malignant phase hypertension: The West Birmingham Malignant Hypertension project

BackgroundPrevious studies have confirmed that cardiac structural and functional abnormalities exist in patients with malignant hypertension (MHT). The effect of long-term blood pressure control in MHT patients on cardiac structure and function is still unknown. MethodsWe performed detailed left ventricle (LV) assessment using two-dimensional (2DE) and three-dimensional (3DE) echocardiography, and tissue Doppler imaging (TDI) in patients with previous MHT (but now in stable phase) who were compared with patients with treated ‘high risk’ hypertension (HHT, but non-MHT) and healthy controls (HC). Vasodilator stress myocardial contrast echocardiography (in addition to wall motion analysis) was used to exclude significant coronary artery disease, as part of our comprehensive echocardiographic assessment. Septal and posterior wall thickness, LV mass index, LV volumes and ejection fraction, mitral valve inflow indices (E, A) mitral annular velocity (S, E′) and left atrial volume index (LAVI), were calculated using 2DE, 3DE, and TDI. MHT patients had good blood pressure control for an average of 144months. ResultsA total of 95 subjects (MHT=15; HHT and HC=40 each) were studied. Both posterior and septal wall thickness were significantly higher in the MHT and hypertensive groups compared to normal controls with no difference between MHT and HHT. No significant difference in LV ejection fraction was found between the 3 groups. Increased LAVI (p<0.05 MHT vs. HC and HHT vs. HC), reduced ‘S’ velocity on TDI (p=0.05 MHT vs. HC and vs.HHT, p<0.001 HHT vs. HC) and higher E/E′ (p=0.029 HHT vs. HC) and lower E/A ratio (p=0.001 MHT vs. HC, p<0.001 HHT vs. HC) values were detected in the two hypertensive groups. ConclusionDespite long-term good blood pressure control, MHT patients have persistent structural and functional changes in LV function on echocardiography, comparable to that seen in HHT.

A rare case of malignant-phase hypertension with pulmonary alveolar hemorrhage

Malignant-phase hypertension is characterized clinically by severe accelerating hypertension with neuroretinopathy or papilledema and by evidence of renal damage. A Japanese male in his early thirties presented with hemoptysis and general fatigue. He had a 5-year history of hypertension, but had not received any treatment. His blood pressure was 290/150mmHg and his serum creatinine level was 8.24mg/dL. Chest X-rays and computed tomography scans of the chest revealed a pulmonary alveolar hemorrhage. He was suspected of having vasculitis syndrome or Goodpasture's syndrome, but his renal biopsy specimen showed malignant nephrosclerosis. Myeloperoxidase antineutrophil cytoplasmic antibody (ANCA), proteinase-3 ANCA and antiglomerular basement membrane antibody were negative. He was treated with a calcium antagonist and a β-blocker, followed by an angiotensin-converting enzyme inhibitor. After the administration of the β-blocker, his blood pressure decreased and his renal function gradually improved. This is a rare case of malignant-phase hypertension with pulmonary alveolar hemorrhage; this condition should be considered in the differential diagnosis in order to avoid unnecessary treatment such as immunosuppressive therapy.

Persistent Macrovascular and Microvascular Dysfunction in Patients With Malignant Hypertension

Endothelial dysfunction is characteristic of patients with essential hypertension, but only limited data are available on different aspects of endothelial function in patients with malignant-phase hypertension. We investigated myocardial perfusion using real-time quantitative myocardial contrast echocardiography with concurrent assessment of macrovascular and microvascular endothelial damage/dysfunction in patients with previous malignant hypertension (but now in stable phase), who were compared with patients with treated "high-risk" hypertension (hypertension) and healthy controls. We measured flow (hyperemia)-mediated dilation and response to glyceryl trinitrate of brachial artery (ultrasound), microvascular (forearm) response to acetylcholine and sodium nitroprusside (laser Doppler), pulse wave velocity, circulating endothelial and endothelial progenitor cells in 15 patients with malignant hypertension, 40 matched patients with hypertension, and 40 healthy controls. Patients with malignant hypertension had impaired endothelial-dependant response to acetylcholine (P<0.001, but not to sodium nitroprusside) compared with hypertension and impaired reaction to both stimuli compared with healthy subjects (P<0.001). Patients with malignant hypertension had increased circulating endothelial cells (P=0.001), endothelial progenitors (P=0.008), and stiffness (P=0.003). Both hypertensive groups had impaired response to hyperemia and glyceryl trinitrate when compared with healthy controls (P<0.05). Both hypertensive groups had similar myocardial perfusion, which was significantly lower than in healthy controls. There were no significant differences in hyperemia and endothelium-independent stimuli between the 2 hypertensive groups. In conclusion, despite fairly well-controlled blood pressure, malignant hypertension patients had more pronounced abnormalities of macrovascular and microvascular function (which seem to be both endothelium dependent and endothelium independent) compared with patients with hypertension and healthy controls.

Improving Survival of Malignant Hypertension Patients Over 40 Years

To examine changing demography and survival of patients with malignant phase hypertension (MHT) over 40 years. Patients from our MHT registry whose survival status on 31 December 2006 was known were included, with analyses conducted based on decade of MHT diagnosis. Four-hundred and forty-six patients with MHT (overall mean (s.d.) age 48.2 (12.9), years; 65.5% male; 64.7% white-European; 20.4% African Caribbean, and 14.8% South-Asian) were included. No significant demographic differences at diagnosis were evident over the 40 years, with the exception of a significant increase (P = 0.001) in the proportion of MHT among ethnic minorities (South-Asian and Afro-Caribbeans). There were no significant differences in mean systolic blood pressure (SBP) at presentation but baseline diastolic BP (DBP) was significantly lower after 1976 (P < 0.0001). The total number of person-years of observation was 5,725.5 years, with a median (interquartile range (IQR)) length of follow-up of 103.8 (31.3-251.2) months. Overall 203 patients (55.6%) died, 125 (32.0%) within 5 years of diagnosis. There was a significant improvement in 5-year survival from 32.0% prior to 1977 to 91.0% for patients diagnosed between 1997 and 2006. SBP and DBP improved significantly during follow-up (P < 0.0001). Multivariate analyses revealed that age, decade of MHT diagnosis, baseline creatinine, and follow-up SBP were independent predictors of survival (all P < 0.0001). Demography and number of new cases of MHT have not changed dramatically over the past 40 years. Five-year post-MHT survival has improved significantly, possibly related to lower BP targets, tighter BP control, and availability of new classes of antihypertensive drugs.

End-organ damage in hypertensive transgenic Ren-2 rats: influence of early and late endothelin receptor blockade

The rat strain transgenic for the murine Ren-2 renin gene (TGR) is defined as a monogenic model of angiotensin II-dependent hypertension with endogenous activation of the renin-angiotensin system. Homozygous males TGR develop malignant hypertension with a strong salt-sensitive component. These animals show severe hypertension, proteinuria and high mortality. Morphological changes of renal parenchyma correspond to chronic ischemic glomerular changes. Heterozygous TGR develop only mild hypertension and thus provide a more suitable model of hypertension regarding to clinical studies. Within the renal parenchyma, secondary focal segmental glomerulosclerosis (FSGS) predominates. High-salt diet in heterozygous animals induces transition from benign to malignant phase of hypertension. In this case, ischemic glomerular changes are superimposed on preexisting secondary FSGS. In the regression model of hypertension (late-onset treatment) the effect of salt intake is attenuated. In homozygous TGR, early selective ET(A) receptor blockade decreased blood pressure and ameliorated end-organ damage. Late selective ET(A) receptor blockade reduced podocyte injury despite final severe hypertension. Survival rate was markedly improved in both regimens with ET(A) selective blockade, while there was only partial improvement with early non-selective blockade. Both bosentan and atrasentan decreased ET-1 levels in both regimens. In heterozygous TGR, early and late ET(A) treatment substantially while ET(A)/ET(B) treatment partially improved survival rate. Significant effect on BP was found with early and late ET(A) blockade, while ET(A)/ET(B) blockade had no effect. Bosentan and atrasentan similarly decreased ET-1 levels on both regimens. In conclusion, selective ET(A) receptor blockade is superior to nonselective ET(A)/ET(B) receptor blockade in attenuating hypertension and end-organ damage. Its effect is more pronounced when applied early in the life.

Circulating Endothelial Cells, Arterial Stiffness, and Cardiovascular Risk Stratification in Hypertension

Given the growing burden of cardiovascular disease, there is increasing interest in strategies to help predict future cardiovascular risk. To investigate the relationship between endothelial damage/dysfunction, arterial stiffness, and their association with predicted risk of future cardiovascular death among patients with hypertension. We studied three patient groups 35 to 74 years old: healthy control subjects (n=63), subjects with high-risk hypertension (HHT) [n=65], and patients with treated, previously diagnosed, malignant-phase hypertension (MHT) [n=43]. We measured comparative indexes of arterial stiffness (stiffness index [SI] using digital volume photoplethysmography), endothelial damage/dysfunction (venous circulating endothelial cells [CECs], immunobead technique), and 5-year predictive risk of future cardiovascular death (Pocock scoring system). CEC counts, SI, and 5-year prediction of cardiovascular death were significantly higher in both hypertension groups (HHT and MHT), compared with healthy control subjects. CEC counts were significantly higher in the MHT group (p<0.05). There was a significant correlation between CECs and SI in the HHT group (r=0.61; p<0.0001) and the MHT group (r=0.59, p<0.0001) and between CEC, SI, and predicted 5-year risk of cardiovascular death in the two hypertension groups. On multiple linear regression analysis, arterial SI and CECs remained as significant predictors of the calculated 5-year risk of cardiovascular death (R2=0.37; p<0.0001). There is a consistent association between CECs, arterial stiffness, and the predictive risk of cardiovascular death among a group of patients with HHT or previously treated MHT. Registration number 05/Q2709/1.

Reply to Kelly et al.

LETTERS TO THE EDITORReply to Kelly et al.Karl F. Hilgers, and Andrea HartnerKarl F. Hilgers, and Andrea HartnerPublished Online:01 May 2007https://doi.org/10.1152/ajprenal.00076.2007MoreSectionsPDF (27 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat reply: We thank Kelly and coworkers (3) for their comments. We agree that some of the Ren-2 animals in our study did develop malignant hypertension, as discussed in our report (see the penultimate paragraph of the discussion in Ref. 1). We included all animals which survived to the end of the study in the final analysis because we feel that the exclusion of animals with malignant hypertension would have confounded the results. First, exclusion before entry in the protocol is not possible because Ren-2 rats can develop malignant hypertension over several months (5). Second, early signs of malignant hypertension such as increased diuresis or weight loss are of little use in diabetic animals and could be used only in normoglycemic controls. A marked weight difference between diabetic and nondiabetic Ren-2 rats is obvious in our study as well as in the reports of Kelly and coworkers (2, 4). Third, exclusion of animals with malignant hypertension based on criteria like blood pressure or renal damage could obviously lead to a bias, especially if malignant hypertension occurs more frequently in one group.We observed some diabetes-induced glomerular matrix expansion superimposed on hypertension but no nodular glomerulosclerosis. The lower mortality in diabetic Ren-2 rats (Fig. 6C in Ref. 1) certainly does not point to more severe kidney damage either. Finally, we are surprised to read in the letter by Kelly and coworkers that they were “always careful to exclude” animals with malignant hypertension. No such statement can be found in their reports (2, 4). A procedure that bears such a high potential to affect the results should not be omitted from the description but needs to be clearly outlined.REFERENCES1 Hartner A, Cordasic N, Klanke B, Wittmann M, Veelken R, Hilgers KF. Renal injury in streptozotocin-diabetic Ren2-transgenic rats is mainly dependent on hypertension, not on diabetes. Am J Physiol Renal Physiol 292: F820–F827, 2007.PubMed | ISI | Google Scholar2 Kelly DJ, Wilkinson-Berka JL, Allen TJ, Cooper ME, Skinner SL. A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR). Kidney Int 54: 343–352, 1998.Crossref | PubMed | ISI | Google Scholar3 Kelly DJ, Wilkinson-Berka JL, Gilbert RE. Progressive diabetic nephropathy in the Ren-2 rat. Am J Physiol Renal Physiol 292: F1662, 2007.Link | ISI | Google Scholar4 Kelly DJ, Zhang Y, Hepper C, Gow RM, Jaworski K, Kemp BE, Wilkinson-Berka JL, Gilbert RE. Protein kinase C beta inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension. Diabetes 52: 512–518, 2003.Crossref | PubMed | ISI | Google Scholar5 Whitworth CE, Fleming S, Cumming AD, Morton JJ, Burns NJ, Williams BC, Mullins JJ. Spontaneous development of malignant phase hypertension in transgenic Ren-2 rats. Kidney Int 46: 1528–1532, 1994.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: K. F. Hilgers, Nephrologische Forschungslabors, Loschgestrasse 8, 91054 Erlangen, Germany (e-mail: [email protected]) Download PDF Previous Back to Top FiguresReferencesRelatedInformation More from this issue > Volume 292Issue 5May 2007Pages F1663-F1663 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/ajprenal.00076.2007History Published online 1 May 2007 Published in print 1 May 2007 Metrics

Assessment of platelet activation indices using the ADVIATM 120 amongst ‘high‐risk’ patients with hypertension

Background. Platelet activation is involved in the pathogenesis of the thrombotic complications of hypertension. Novel surrogate markers of platelet activation (mean platelet volume (MPV), mean platelet component (MPC, measure of platelet density), platelet component distribution width (PCDW, a marker of platelet shape change) and the number of platelet clumps) have been related to cardiovascular risk. We hypothesized a stepwise increase in these platelet activation indices between healthy controls (HC, n = 60), ‘high‐risk’ essential hypertensive subjects (HBP, n = 45) and treated, previously diagnosed patients with malignant phase hypertension (MHT, n = 45).Methods. In a cross‐sectional study, we measured comparative platelet counts and indices of platelet activation (MPV, MPC, PCDW and the number of platelet clumps) using the Bayer ADVIATM haematology system, in our three study groups.Results. There was a stepwise increase in MPV (P = 0.0002) and MPM (P = 0.03), and a stepwise decrease in the MPC (P = 0.03) and PCDW (P = 0.001) across the three study groups, despite similarities in platelet count. These differences were only significantly different (on post‐hoc analysis) between the healthy controls and the MHT group. On multivariate analysis, there was a significant relationship (R2 = 66.5%; P<0.0001) between the MPV and the PCDW (P<0.0001), systolic blood pressure (P = 0.008) and platelet count (P<0.0001).Conclusion. There is a stepwise increase in platelet activation indices, despite similar platelet counts, with increasing severity of hypertensive disease. This may contribute to the pathogenesis of thrombosis‐related complications in hypertension.

Quantification of topological changes in retinal vascular architecture in essential and malignant hypertension

Grading of hypertension severity by fundoscopic appearance is difficult and inaccurate. We investigated whether essential hypertension (EHT) and malignant phase hypertension (MHT) were associated with quantifiable abnormalities of the topology and architecture of the retinal circulation. The topology and architecture of the retinal microvasculature were compared in images from 20 normotensive subjects, 20 patients with EHT and 20 patients with MHT. Digitized retinal photographs were analysed by a novel multiscale image analysis method using a semi-automated program to quantify geometrical and topological properties of arteriolar and venular trees. EHT was associated with an increase in the arteriolar length-to-diameter ratio (P < 0.01). There were also alterations in arteriolar topology indicative of rarefaction, including a marked reduction in the number of terminal branches in EHT (P < 0.01). These changes in the arteriolar network were exaggerated in MHT and there was also increased venular tortuosity and venular rarefaction in MHT compared with normotensive subjects. Hypertension is associated with marked topological alterations in the retinal vasculature, and quantification of these changes may be a useful novel approach to the assessment of target organ damage in hypertension.

Chronic endothelin receptor blockade reduces end-organ damage independently of blood pressure effects in salt-loaded heterozygous Ren-2 transgenic rats.

The present study was performed to evaluate the role of an interaction between the endothelin (ET) and the renin-angiotensin systems (RAS) in the development and maintenance of hypertension and in hypertension-associated end-organ damage in heterozygous male and female transgenic rats harboring the mouse Ren-2 renin gene (TGR). Twenty-eight days old heterozygous TGR and age-matched transgene-negative normotensive Hannover Sprague-Dawley rats (HanSD) were randomly assigned to groups with normal-salt (NS) or high-salt (HS) intake. Nonselective ET(A)/ET(B) receptor blockade was achieved with bosentan (100 mg.kg(-1).day(-1)). All male and female HanSD as well as heterozygous TGR on NS exhibited 100 % survival rate until 180 days of age (end of experiment). HS diet in heterozygous TGR induced a transition from benign to malignant phase hypertension. The survival rates in male and in female heterozygous TGR on the HS diet were 46 % and 80 %, respectively, and were significantly improved by administration of bosentan to 76 % and 97 %, respectively. Treatment with bosentan did not influence either the course of hypertension (measured by plethysmography in conscious animals) or the final levels of blood pressure (measured by a direct method in anesthetized rats) in any of the experimental groups of HanSD or TGR. Administration of bosentan in heterozygous TGR fed the HS diet markedly reduced proteinuria, glomerulosclerosis and attenuated the development of cardiac hypertrophy compared with untreated TGR. Our data show that the ET receptor blockade markedly improves the survival rate and ameliorates end-organ damage in heterozygous TGR exposed to HS diet. These findings indicate that the interaction between the RAS and ET systems plays an important role in the development of hypertension-associated end-organ damage in TGR exposed to salt-loading.

Echocardiographic changes in patients with malignant phase hypertension: the West Birmingham Malignant Hypertension Register.

In order to study the echocardiographic abnormalities in consecutive patients with malignant phase hypertension (MHT), we reviewed echocardiograms of 31 patients (23 male; mean age 52+/-14 years) with MHT who were admitted to our unit. Trans-thoracic echocardiography was carried out in all patients, and echocardiographic measurements were compared with those of 39 patients (30 male; mean age 54+/-10 years) with controlled nonmalignant essential hypertension, and 32 (19 male; mean age 51+/-10 years) healthy normotensive volunteers. Patients with MHT had a significantly higher mean systolic and diastolic blood pressure (P<0.001) compared to the other two groups. MHT patients had significantly greater mean left atrial dimensions (P=0.002), as well as aortic root dimensions (P=0.01) and left ventricular (LV) dimensions (with the exception of the diastolic internal diameter) (P<0.001). MHT patients also had a mean larger LV mass and LV mass index (both P<0.001) when compared to the other two groups. The mean ejection fraction was also lower in the MHT group (P<0.001). In conclusion, patients with MHT have significant cardiac hypertrophy, in association with systolic dysfunction and dilated left atria, irrespective of the duration of known hypertension. These abnormalities may predispose MHT patients to cardiovascular complications including heart failure and cardiac arrhythmias, such as atrial fibrillation.