ArticlePDF AvailableLiterature Review

Malignant hypertension: New aspects of an old clinical entity

December 2015
Polish Archives of Internal Medicine 126(1-2)

December 2015
126(1-2)

DOI:10.20452/pamw.3276

Authors:

Tomasz J Guzik

The University of Edinburgh

Tomasz P. Mikołajczyk

Jagiellonian University

Show all 6 authorsHide

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

Postulated pathophysiological mechanisms of malignant hypertension

…

Urine aldosterone excretion in patients with essential hypertension and malignant hypertension. Adapted from Laragh et al. 8

…

year survival of patients with malignant hypertension by the year of diagnosis of malignant hypertension in a prospective registry of 446 patients with malignant hypertension attending the City Hospital in Birmingham, United Kingdom. Adapted from Lane et al. 5

…

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POLSKIE ARCHIWUM MEDYCYNY WEWNĘTRZNEJ

2016; 126 (1-2)

MHT is associated with failure in BP autoregu-

lation and develops when the mean arterial pres-

sure (MAP) reaches a critical level of 150 mmHg,

as reported in experimental animals. Fibrinoid ne-

crosis appears in the arterial walls, which may be

caused by vasoactive factor(s) or may be a non-

speciﬁc consequence of very high BP.1

In patients with MHT, very high systolic BP,

and in particular signiﬁcantly elevated diastolic

BP, are surrogate markers of increased peripheral

vascular resistance associated with an increase in

MAP, an abnormal nonpulsatile component of BP.

Even though the introduction of modern mul-

tidrug antihypertensive therapy has resulted in

better BP control and markedly improved prog-

nosis, MHT is still a life-threating manifestation

of hypertension and represents a clinical enti-

ty characterized by high cardiovascular risk and

Introduction

Malignant hypertension (MHT),

also known as accelerated-malignant hyperten-

sion or malignant-phase hypertension, is the most

severe form of hypertension; it is deﬁned clinically

as high blood pressure (BP) associated with bilat-

eral retinal ﬂame-shaped hemorrhages, exudates,

or cotton wool spots, with or without papillede-

ma. In the 2010 revision of the Dutch guidelines

for the management of hypertensive crisis, van

den Born et al

replaced the term “malignant hy-

pertension” with “hypertensive crisis with reti-

nopathy”, which was followed by Kaplan and Vic-

tor in the 2015 edition of Kaplan’s Clinical Hyper-

tension. e authors concluded that the presence

of retinopathy may allow other target organs to

be included, making the description of this type

of emergency more accurate.1-3

Correspondence to:

Aleksander Prejbisz, MD, PhD,

Klinika Nadciśnienia Tętniczego,

Instytut Kardiologii, ul. Alpejska

42, 04-628 Warszawa, Poland,

phone: +48 22 343 43 39,

e-mail: a.prejbisz@ikard.pl

Received: November 12, 2015.

Accepted: November 16, 2015.

Published online:

December 10, 2015.

Conflict of interest: none declared.

Pol Arch Med Wewn. 2016;

126 (1-2): 86-93

Kraków 2016

KEY WORDS

malignant

hypertension,

pathogenesis,

prevalence, treatment

ABSTRACT

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.

REVIEW ARTICLE

Malignant hypertension: new aspects of an old

clinical entity

AndrzejJanuszewicz

, TomaszGuzik

, AleksanderPrejbisz

TomaszMikołajczyk

, GrzegorzOsmenda

, WłodzimierzJanuszewicz

1 Department of Hypertension, Institute of Cardiology, Warsaw, Poland

2 Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Kraków, Poland

3 Warsaw, Poland

REVIEW ARTICLE Malignant hypertension: new aspects of an old clinical entity 87

admissions for MHT, identifying all hospitaliza-

tions between 2000 and 2011 during which a pri-

mary diagnosis of MHT was recorded.

e re-

sults clearly demonstrated a much higher rate of

increase in the number of hospitalizations with

a primary discharge diagnosis of MHT during

this time period. e rate of annual hospitaliza-

tions for MHT remained stable before 2007, but

then started to signiﬁcantly increase at an esti-

mated rate of 2700 per year.

One explanation of

the results is that the reported data represented

a true change in the epidemiology of hyperten-

sive emergencies. Another cause of the change,

which is much more likely, is that this abrupt in-

crease resulted from a change in coding practic-

es in the United States.7

Pathophysiological mechanisms

Possible patho-

physiological mechanisms for the development

of MHT have been proposed, including rapid-

ly increasing BP, pressure diuresis and natriure-

sis, severe renal vasoconstriction, and ischemia

(

FIGURE 1

). In addition, activation of the renin–an-

giotensin–aldosterone system (

FIGURE 2

), microan-

giopathy, hemolytic anemia, and development of

retinopathy are observed in MHT. e vascular

lesions of MHT include myointimal proliferation

and ﬁbrinoid necrosis.8-21

The immune system in malignant hypertension

While the role of endothelial dysfunction and kid-

ney damage in MHT has been addressed by nu-

merous other reviews, recent studies have indi-

cated that the immune system, and in particular

T cells, play a crucial role in the development of

elevated risk of developing end-stage renal dis-

ease (ESRD) in a long-term follow-up.1

Incidence of malignant hypertension

Despite the

vast range of antihypertensive agents and eﬀec-

tive BP control, MHT remains an important clin-

ical entity. Although its frequency is very low, the

absolute number of new cases has not changed

much over the past decades, as documented by

recent studies.1

e study by Lane et al5 examined the chang-

ing demography and survival of 446 patients with

MHT attending the City Hospital in Birmingham,

United Kingdom, from 1964 to 2006, with a me-

dian follow-up of 103.8 months. In this largest

prospective analysis in the world literature, the

number of new cases of MHT has not changed

substantially over 40 years. e study supports

the concept that MHT is not a vanishing disease,

with a relatively stable number of 2 to 3 new cas-

es of MHT per 100 000 head of population per

year.5 e demography of the disease has not al-

tered during the follow-up, with no signiﬁcant dif-

ferences in the mean age at diagnosis, but with

a slight predominance in men. It is of note that

during the follow-up, there was a signiﬁcant in-

crease in the proportion of ethnic minorities, in-

cluding South-Asians and Afro-Caribbeans, and a

signiﬁcant decrease in white Europeans.

Another

smaller study evaluating European cohorts dem-

onstrated a fairly stable incidence of MHT, with

2 to 3 new cases per 100 000 head of population

over the past 30 years.6

A recent retrospective cohort study investigat-

ed national trends in the United States in hospital

FIGURE 1 Postulated

pathophysiological

mechanisms of malignant

hypertension

excessive increase in

blood pressure

smoking

endothelial

dysfunction

key factors in the

pathogenesis of malignant

hypertension

oxidative stress ↑

angiotensin II ↑

endothelin 1 ↑

vasopressin ↑

platelet activation

aldosterone ↑

sympathetic nervous

system ↑

inflammatory and

immune mechanisms

proinflammatory

cytokines ↑

POLSKIE ARCHIWUM MEDYCYNY WEWNĘTRZNEJ

2016; 126 (1-2)

immunohistochemical analysis of biopsied re

nal tissue revealed a higher inﬁltration of T cells,

both CD4+ and CD8+, in patients with hyperten-

sive nephrosclerosis, compared with normoten-

sive controls. In patients with psoriasis treated

with mycophenolate mofetil targeting B and T

cells has shown to reduce BP. It is possible that

immunomodulating agents will emerge in the fu-

ture as a potential treatment option for patients

with MHT, especially in the context of concom-

itant immune disorders. However, at present,

there is no suﬃcient clinical evidence to support

such an approach.26,27

Clinical features

MHT may be accompanied by

various symptoms and complications, the most

characteristic being microangiopathic lesions or

renal dysfunction (FIGURE 3). Acute lesions in the

retinal fundus may include arteriolar spasm, reti-

nal edema, hemorrhages, exudates and papillede-

ma, and engorged retinal veins.1

In 28% of patients with MHT, van den Born et

al28 found thrombotic microangiopathy, charac-

terized by thromboses of small vessels, intravas-

cular hemolysis with fragmented red blood cells,

elevated lactic dehydrogenase, and consumption

of platelets. Less common clinical presentations

may include ﬁbrinoid necrosis within abdominal

arteries producing major gastrointestinal tract in-

farction with an acute abdomen, necrotizing vas-

culitis as a feature of lupus, polyarteritis nodosa,

or Takayasu arteritis.29-33

Urine may contain protein and red cells. In a

few patients, acute oliguric renal failure may be

the presenting manifestation, and various fea-

tures of renal dysfunction (including protein-

uria) may be present. Approximately half of pa-

tients with MHT have hypokalemia, reﬂecting

experimental hypertension and vascular pathol-

ogy. In addition, our preliminary studies in hu-

mans have indicated that immune dysregulation

is particularly evident in hypertension.

22,23

Mice

lacking T and B lymphocytes (Rag1–/–) were re-

sistant to the development of severe hyperten-

sion in both angiotensin II and desoxycorticoste-

rone acetate-salt-induced hypertension models,

and this eﬀect was greatly mediated by T-cell ac-

tivation.22-24 Subsequent studies have indicated

that a complex network of interactions between

T cells, dendritic cells, monocytes, and B cells

may be involved in hypertension. A mild form of

hypertension develops in the absence of T cells,

while severe hypertension is completely prevent-

ed. is could indicate a possible involvement of

an inﬂammatory and immune mechanism, par-

ticularly in MHT.22-24

Activated memory and eﬀector T lympho-

cytes responding to the prohypertensive fac-

tors are able to inﬁltrate the adventitia and peri-

vascular fat, and possibly also the renal tissues

or even the central nervous system. In the peri-

vascular adipose tissue and in the kidney, these

cells release proinﬂammatory cytokines such

as interleukin (IL) 17, tumor necrosing factor α

(TNF-α), and interferon γ. us, the targeting

of TNF-α, IL-17, or chemotactic molecules such

as the RANTES/CCR5 axis might be considered,

and may become useful in the future manage-

ment of resistant hypertension.22,25

Evidence of T cell-derived inﬂammation in

hypertension is also slowly accumulating for

humans.26 ere is an increased fraction of im-

munosenescent, cytotoxic T cells in the circu-

lation of patients with hypertension compared

with normotensive subjects. Plasma TNF-α

and IL-6 levels are correlated with BP, and a

FIGURE 2 Urine

aldosterone excretion in

patients with essential

hypertension and

malignant hypertension.

Adapted from Laragh

et al.8

essential hypertension

3000

2500

2000

1500

1000

500

malignant hypertension

evaluated patients

aldosterone

g/24 h

REVIEW ARTICLE Malignant hypertension: new aspects of an old clinical entity 89

patients suspected of ﬁbromuscular dysplasia, or

in older patients with extensive atherosclerosis.

Idiopathic IgA nephropathy has also been report-

ed as a possible cause of MHT.1,34,35

Rarely, primary hyperaldosteronism may be

associated with MHT, as documented by a small

number of cases. A recent report described a

22-year-old patient with MHT, associated with

primary hyperaldosteronism and LVH mimick-

ing hypertrophic cardiomyopathy.

35,36

Primary al-

dosteronism is typically deﬁned by an increased

plasma aldosterone level and suppressed plasma

renin activity through a negative feedback mech-

anism. Hence, primary aldosteronism and MHT

are at opposite ends of the renin spectrum, and

their coexistence is thought to be very rare.36,37

ere have also been sporadic reports of MHT

in patients with pheochromocytoma and renin-

-secreting tumors.38-40

It is of note that, in most cases, MHT is accom-

panied by various life-threatening symptoms,

signs, and associated complications. However, it

is not uncommon to see patients denying any pri

or symptoms in the end stages of the hyperten-

sive disease. In such cases, MHT is often unrec-

ognized until a later stage in the progress of the

disease, when clinical symptoms are becoming ap-

parent and patients are symptomatic.1

Impact of malignant hypertension on the heart

Afew

studies have conﬁrmed that structural and func-

tional cardiac abnormalities are present in pa-

tients with MHT, indicating features of cardiac

damage and compensatory remodeling. However,

secondary aldosteronism from increased renin

secretion induced by intrarenal ischemia. Hypo-

natremia is common and may be severe.1

Multiple markers of inﬂammation, coagulation,

platelet activation, and ﬁbrinolysis were found in

the blood of patients with various types of hyper-

tensive emergencies, compared with the levels ob-

served in normotensive controls.2,11

An electrocardiogram usually shows evidence

of left ventricular hypertrophy (LVH). Echocar-

diography may show impaired systolic and dia-

stolic function and delayed mitral valve opening.

Regression of these abnormalities usually occurs

after lowering of BP by antihypertensive therapy.

Identifiable causes of malignant hypertension

In pa-

tients with MHT, after an acute phase, an appro-

priate evaluation of identiﬁable causes of hyper-

tension should be performed as quickly as possi-

ble. It is preferable to obtain the necessary blood

and urine samples for required laboratory stud-

ies before instituting therapies that may mark-

edly complicate subsequent evaluation. Howev-

er, none of these procedures should delay eﬀec-

tive therapy. MHT usually occurs in patients with

long-standing preexisting hypertension and may

be associated with a recent cessation of antihyper-

tensive therapy. However, any form of secondary

hypertension may progress to MHT.1-3

Renovascular hypertension is the most likely

secondary cause, and, in a large series of patients

with MHT, renal artery stenosis was the under-

lying cause of hypertension in 3.6% of the cas-

es. It should in particular be sought in younger

headache

visual disturbances

gastrointestinal symptoms

heart failure

neurological sequelae (encephalopathy)

left ventricular hypertrophy

mild-to-moderate renal impairment

severe renal impairment

microangiophatic hemolytic anemia

100

frequency, %

FIGURE 3 Presenting

symptoms and associated

complications in patients

with hypertensive crisis

and advanced

retinopathy;

gastrointestinal

symptoms: nausea,

vomiting, weight loss;

mild-to-moderate renal

impairment, serum

creatinine concentration

115–300 μmol/l; severe

renal impairment, serum

creatinine concentration

>300 μmol/l. Adapted

from van den Born.1

POLSKIE ARCHIWUM MEDYCYNY WEWNĘTRZNEJ

2016; 126 (1-2)

years of follow-up, respectively. e study con-

ﬁrmed that the severity of renal failure at presen-

tation, worse BP control during follow--up, and

severity of proteinuria were important prognos-

tic factors for long-term renal outcomes.46

In another study, van den Born et al28 reported

a relatively high prevalence of microangiopath-

ic hemolysis in patients with MHT and showed

that, in those subjects, microangiopathic hemo-

lysis was an important indicator of both renal in-

suﬃciency and recovery.

It has been reported that, when intensive an-

tihypertensive therapy was started in patients

with MHT, renal function remained unchanged

or improved in nearly half of those with initial

renal insuﬃciency. In one series of 54 patients

with MHT requiring dialysis, 22% of the subjects

recovered suﬃcient renal function to allow with-

drawal of dialysis.47,4 8

Considering that the activation of the renin–

-angiotensin–aldosterone system is an impor-

tant pathogenic mechanism in MHT and that

drugs aﬀecting the system have speciﬁc antipro-

teinuric properties, a long-term treatment of pa-

tients with MHT should be based mainly on this

type of agents.

Management MHT is a hypertensive emergen-

cy, and patients should receive immediate anti-

hypertensive treatment owing to a high risk of

renal failure, stroke, myocardial infarction, and

heart failure.

Following the 2013 guidelines on hyperten-

sion from the European Society of Hypertension

and European Society of Cardiology, the current

treatment is based on agents that can be admin-

istered by intravenous infusion and titrated ac-

cording to response, avoiding abrupt falls in BP

and excessive hypotension.3

e goal of the immediate therapy should be to

lower diastolic BP to approximately 110 mmHg.

ere is a consensus opinion to reduce MAP by

no more than 25% during the acute phase in or-

der to avoid cerebral hypoperfusion. Labetalol,

sodium nitroprusside, nicardipine, nitrates, and

furosemide are listed among the most frequent-

ly used intravenous drugs. However, due to the

low incidence of MHT, there are no data to doc-

ument which of these drugs is best, or whether

their use is followed by a decrease in morbidity

and mortality in this group of patients.1

e study by Immink et al

showed a signiﬁcant

diﬀerence in the decrease of systemic vascular re-

sistance during the administration of sodium ni-

troprusside and labetalol (43% and 13%, respec-

tively) in patients with MHT. ese may be attrib-

uted to diﬀerential eﬀects of these drug classes

on systemic vascular resistance and heart rate in

patients with MHT.

It has also been recognized

that antihypertensive drugs diﬀer in their capac-

ity to reduce central BP, whereas their eﬀects on

peripheral BP may be similar.4

Taken together, in the absence of deﬁnite ev-

idence, clinicians must continue to administer

these studies have had major limitations, such as

a short follow-up duration and the lack of use of

3-dimensional echocardiography.41-43

LVH, observed in patients with new-onset

MHT, may at least partly reﬂect an adaptive re-

sponse to persistently elevated BP, and its pres-

ence is associated with unfavorable prognosis.

Indeed, the duration of the follow-up and the

quality of BP control had a strong direct eﬀect

on prognosis in patients with MHT presenting

with LVH.41-43

In contrast to previous observations based on

a cohort of MHT patients with less rigorous BP

control, the study by Shantsila et al41 showed that

patients with adequately controlled MHT have a

similar degree of LVH to that in control subjects

without MHT. e study documented that all pa-

tients had preserved left ventricular ejection frac-

tion, despite a median 12-year history of MHT,

which did not diﬀer from the values observed in

the control group. In addition, the systolic and

diastolic function indices were out of range, but

did not diﬀer between the MHT and non-MHT

groups.

ese ﬁndings appear to be similar to

the observations made by Gosse et al,

who dem-

onstrated a recovery of the left ventricular func-

tion with treatment during a short follow-up.

Taken together, the above observations prove

that, despite good long-term BP control, patients

with MHT have persistent structural and func-

tional changes in the left ventricle on echocar-

diography, comparable to those observed in con-

trol non-MHT patients.

Long-term renal outcome

Although the survival

rate of patients with MHT has considerably im-

proved with the introduction of antihyperten-

sive therapy, MHT is frequently complicated by

renal insuﬃciency, and ESRD still remains a sig-

niﬁcant cause of morbidity and mortality in this

patient group. e STAT study

demonstrated

that, in patients hospitalized with acute severe

hypertension, the presence of acute kidney injury

was associated with a greater risk of serious out-

comes, including mortality and additional end-

-organ damage.44

A retrospective analysis of 120 patients with

MHT conducted in the Netherlands showed that

patients with MHT had a markedly increased risk

of ESRD after the acute phase.45 During a medi-

an follow-up period of 67 months, 31% of the pa-

tients reached the primary endpoint (ESRD), 15%

reached the secondary endpoint (all-cause mor-

tality), and 24% required kidney replacement. Af-

ter the acute phase, initial serum creatinine lev-

els and BP during follow-up were the main pre-

dictors of future ESRD.

In another retrospective study, Gonzalez etal

reported on long-term renal outcomes in a cohort

of 197 patients with MHT. Renal involvement was

a major component of MHT, with 63% of the pa-

tients presenting with acute renal function im-

pairment. e probability of renal survival in the

entire cohort was 84% and 72% after 5 and 10

REVIEW ARTICLE Malignant hypertension: new aspects of an old clinical entity 91

history of MHT remain at increased risk, and the

annual incidence of all-cause mortality was high-

er in MHT patients compared with that in nor-

motensive and hypertensive controls.

Taken together, despite satisfactory BP con-

trol with modern antihypertensive therapy, MHT

continues to be an important clinical entity and

may signiﬁcantly contribute to an increase in to-

tal cardiovascular risk.1,14,50-55

Summary

In summary, MHT is not a “vanishing

disease”, having a relatively stable number of cas-

es per year, but its prognosis and survival rates

have signiﬁcantly improved owing to earlier detec-

tion, tighter BP control, lower BP targets, better

choice of antihypertensive drugs, and availability

of hemodialysis and renal transplantation. How-

ever, despite the vast range of antihypertensive

agents and eﬀective BP control, MHT remains a

signiﬁcant clinical challenge.

Acknowledgments We would like to thank Mrs.

L. Kozłowska and Mrs. M. Ciechanowska for their

help during preparation of this manuscript. e

research of TG and TM is funded by the Na-

tional Science Centre, Poland (NCN 2011/03/B/

NZ4/02454).

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parenteral drugs to markedly lower elevated BP

in patients with a hypertensive emergency. How-

ever, this should be done carefully, under close su-

pervision, and with the choice of drugs that allow

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1-3

Prognosis

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e results from the largest prospective regis-

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as 91% for patients diagnosed between 1997 and

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e mortality rate was similar among white

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In addition, a retrospective cohort study that

investigated national trends in the United States

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crease in the mortality rate by 36% among pa-

tients diagnosed with MHT after 2007.7

e study by Amraoui et al50 documented that,

despite a considerable improvement in the sur-

vival rate over the past decades, patients with a

FIGURE 4 5-year

survival of patients with

malignant hypertension

by the year of diagnosis

of malignant

hypertension in a

prospective registry of

446 patients with

malignant hypertension

attending the City

Hospital in Birmingham,

United Kingdom.

Adapted from Lane et al.5

20 30 50 7010040608090 100

year of diagnosis

5-year survival, %

<1967

1967–1976

1977–1986

1987–1996

1997–2006

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ARTYKUŁ POGLĄDOWY Nadciśnienie tętnicze złośliwe – nowe aspekty starej jednostki klinicznej 93

Adres do korespondencji:

dr n. med. Aleksander Prejbisz, Klinika

Nadciśnienia Tętniczego, Instytut

Kardiologii, Warszawa, ul. Alpejska 42,

04-628, Warszawa, tel.: 22 343 43

39, e-mail: a.prejbisz@ikard.pl

Praca wpłynęła: 12.11.2015.

Przyjęta do druku: 16.11.2015.

Publikacja online: 10.12.2015.

Nie zgłoszono sprzeczności

interesów.

Pol Arch Med Wewn. 2016;

126 (1-2): 86-93

Kraków 2016

SŁOWA KLUczOWe

leczenie, nadciśnienie

tętnicze złośliwe,

patogeneza,

występowanie

STReSzczenie

Nadciśnienie tętnicze złośliwe (malignant hypertension – MHT), nazywane także przyspieszonym

nadciśnieniem tętniczym złośliwym lub fazą złośliwą nadciśnienia tętniczego, jest najcięższą postacią

nadciśnienia tętniczego. Definiuje się je jako istotnie podwyższone wartości ciśnienia tętniczego z towa-

rzyszącymi zmianami na dnie oka (płomykowate wybroczyny, wysięki, ogniska waty, z lub bez obrzęku

tarczy nerwu wzrokowego). Pomimo dostępności licznych leków hipotensyjnych MHT pozostaje ważnym

problem klinicznym. Częstość jego występowania jest bardzo niska, jednak bezwzględna liczba nowych

przypadków nie zmieniła się na przestrzeni ostatnich dekad. Chociaż rola aktywacji układu renina-an-

giotensyna-aldosteron i dysfunkcji śródbłonka w patogenezie MHT została dobrze udokumentowana,

wyniki ostatnich badań wskazują, że także układ odpornościowy może odgrywać istotną rolę w rozwoju

tej choroby. Chorzy z MHT charakteryzują się nasilonymi powikłaniami narządowymi nadciśnienia tętni-

czego, w tym nieprawidłowościami strukturalnymi i funkcjonalnymi serca. Częstymi powikłaniami MHT

są upośledzenie funkcji nerek oraz schyłkowa niewydolność nerek. Przeżycie chorych z MHT poprawiło

się znacząco wraz ze zwiększeniem dostępności leczenia hipotensyjnego, niemniej jednak upośledzenie

funkcji nerek i rozwój schyłkowej niewydolności nerek wciąż stanowią istotną przyczynę chorobowo-

ści i śmiertelności w tej grupie chorych. Podsumowując, MHT nie jest „znikającą chorobą”, ponieważ

charakteryzuje się stałą liczbą nowych przypadków rocznie. Rokowanie i przeżycie pacjentów z MHT

poprawiło się natomiast znacząco w wyniku wcześniejszego rozpoznania, ściślejszej kontroli ciśnienia

tętniczego, niższych wartości docelowych ciśnienia tętniczego, większego wyboru leków hipotensyjnych

oraz zwiększenia dostępności leczenia nerkozastępczego i transplantacji nerek.

ARTYKUŁ POGLĄDOWY

Nadciśnienie tętnicze złośliwe – nowe aspekty

starej jednostki klinicznej

AndrzejJanuszewicz

, TomaszGuzik

, AleksanderPrejbisz

TomaszMikołajczyk

, GrzegorzOsmenda

, WłodzimierzJanuszewicz

1 Klinika Nadciśnienia Tętniczego, Instytut Kardiologii, Warszawa

2 Katedra Chorób Wewnętrznych i Medycyny Wsi, Uniwersytet Jagielloński, Collegium Medicum, Kraków

3 Warszawa

Serum Elabela expression is decreased in hypertensive patients and could be associated with the progression of hypertensive renal damage

Article

Full-text available

Feb 2024

Background Elabela, a recently discovered hormonal peptide containing 32 amino acids, is a ligand for the apelin receptor. It can lower blood pressure and attenuate renal fibrosis. However, the clinicopathological relationship between Elabela level and renal damage caused by benign hypertension (BHT) and malignant hypertension (MHT) has not been elucidated. Therefore, we investigated the clinicopathological correlation between serum Elabela level and renal damage caused by BHT and MHT. Methods The participants comprised 50 patients and 25 age-matched healthy adults. The 50 patients were separated into two groups: MHT (n = 25) and BHT groups (n = 25). We analyzed their medical histories, demographics, and clinical examinations, including physical and laboratory tests. Results The results showed that serum Elabela level decreased gradually with a continuous increase in blood pressure from the healthy control group, BHT, to MHT. Moreover, Elabela levels negatively correlated with BMI (R = − 0.27, P = 0.02), SBP (r = − 0.64, P < 0.01), DBP (r = − 0.58, P < 0.01), uric acid (r = − 0.39, P < 0.01), bun (r = − 0.53, P < 0.01), and Scr (r = − 0.53 P < 0.01) but positively correlated with eGFR (r = 0.54, P < 0.01). Stepwise multivariate linear regression analysis showed that SBP was the variable most related to Elabela (t = − 5.592, P < 0.01). Conclusions Serum Elabela levels decreased in patients with hypertension, especially malignant hypertension, and has the potential to be a marker of hypertension-related kidney damage.

Serum Elabela expression is decreased in hypertensive patients and could be associated with the progression of hypertensive renal damage

Preprint

Full-text available

Oct 2023

Background Elabela, a recently discovered hormonal peptide containing 32 amino acids, is a ligand for the apelin receptor. It can lower blood pressure and attenuate renal fibrosis. However, the clinicopathological relationship between the Elabela level and renal damage caused by benign hypertension (BHT) and malignant hypertension (MHT) has not been elucidated. Therefore, we discussed the clinicopathological correlation between the serum Elabela level and renal damage caused by BHT and MHT in patients. Methods The participants comprised 50 patients and 25 age-matched healthy adults. The 50 patients were separated into two groups: the MHT (n = 25) and BHT groups (n = 25). We analyzed their medical histories, demographics, and clinical examinations, including physical and laboratory tests. Results The results showed that the serum Elabela level decreased gradually with a continuous increase in blood pressure from the healthy control group, BHT, to MHT. Moreover, the Elabela levels negatively correlated with BMI(R = − 0.27, P = 0.02), SBP (R = − 0.64, P < 0.01), DBP (R = − 0.58, P < 0.01), Uric acid(R = − 0.39, P < 0.01), BUN (R = − 0.53, P < 0.01), and Scr (R = − 0.53 P < 0.01) but positively correlated with eGFR (R = 0.54, P < 0.01). Stepwise multivariate linear regression analysis showed that SBP was the variable most related to Elabela (t = − 7.029, P < 0.01). Conclusions Serum Elabela levels decreased in patients with hypertension, especially malignant hypertension, and had a significant negative correlation with systolic blood pressure. Trial registration: retrospectively registered approval number:2020076.

A case of malignant nephrosclerosis occurring with serum renin in the normal range

Article

Aug 2022

A 37-year-old Japanese man was admitted to our hospital for evaluation of severe hypertension and visual impairment. His serum creatinine was 4.16 mg/dL. Plasma renin activity was normal (2.7 ng/mL/h), but plasma aldosterone concentration was elevated (27.2 ng/dL). A kidney biopsy showed concentric subendothelial edematous thickening of the arterioles (onion skin pattern) with luminal narrowing or obstruction, and malignant nephrosclerosis was diagnosed. Antihypertensive therapies, including an angiotensin II receptor blocker and spironolactone, were administered and effectively preserved kidney function and normalized blood pressure. This case indicates that hyperaldosteronemia in the presence of normal renin levels might also cause malignant hypertension.

Assessment of knowledge and attitude and practice towards malignant hypertension among interns in Saudi Arabia, 2018

Article

Oct 2018

Clinical characteristics and outcomes of a patient population with atypical hemolytic uremic syndrome and malignant hypertension: analysis from the Global aHUS registry

Article

Full-text available

Sep 2022
J NEPHROL

Introduction Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) often caused by alternative complement dysregulation. Patients with aHUS can present with malignant hypertension (MHT), which may also cause TMA. Methods This analysis of the Global aHUS Registry (NCT01522183) assessed demographics and clinical characteristics in eculizumab-treated and not-treated patients with aHUS, with ( n = 71) and without ( n = 1026) malignant hypertension, to further elucidate the potential relationship between aHUS and malignant hypertension. Results While demographics were similar, patients with aHUS + malignant hypertension had an increased need for renal replacement therapy, including kidney transplantation (47% vs 32%), and more pathogenic variants/anti-complement factor H antibodies (56% vs 37%) than those without malignant hypertension. Not-treated patients with malignant hypertension had the highest incidence of variants/antibodies (65%) and a greater need for kidney transplantation than treated patients with malignant hypertension (65% vs none). In a multivariate analysis, the risk of end-stage kidney disease or death was similar between not-treated patients irrespective of malignant hypertension and was significantly reduced in treated vs not-treated patients with aHUS + malignant hypertension (adjusted HR (95% CI), 0.11 [0.01–0.87], P = 0.036). Conclusions These results confirm the high severity and poor prognosis of untreated aHUS and suggest that eculizumab is effective in patients with aHUS ± malignant hypertension. Furthermore, these data highlight the importance of accurate, timely diagnosis and treatment in these populations and support consideration of aHUS in patients with malignant hypertension and TMA. Trial registration details Atypical Hemolytic-Uremic Syndrome (aHUS) Registry. Registry number: NCT01522183 (first listed 31st January, 2012; start date 30th April, 2012). Graphical abstract

Malignant Hypertension Complicated with Necrotizing Pancreatitis After Starting Treatment: A Case Report

Article

Full-text available

Jan 2022

Patient: Male, 32-year-old Final Diagnosis: Malignant hypertension Symptoms: Epigastric pain Medication: — Clinical Procedure: — Specialty: Nephrology Objective Unusual clinical course Background Malignant hypertension (MHT), one of the severest forms of hypertension, can have deleterious effects on various organs, such as renal failure, retinopathy, and encephalopathy. These types of organ damage are common complications of MHT, but in several previous cases, damage to other organs, such as the gastrointestinal tract or pancreas, resulting from small vessel lesions, has also been reported, and these cases have had severe clinical outcomes and a poor prognosis. Case Report A 32-year-old male patient with untreated hypertension of a 5-year duration presented with breathlessness and edema. His blood pressure was 220/144 mmHg, and he had renal dysfunction, congestive heart failure, and hypertensive retinopathy. He immediately received treatment, including antihypertensive agents and intermittent hemodialysis, but experienced epigastric pain for several days. A cystic lesion appeared in the pancreatic head, and his serum pancreatic enzymes were elevated. Based on these findings, acute pancreatitis with a cystic lesion was diagnosed. He first received fluid management, pain control, and parenteral nutrition but experienced 2 relapses. Finally, he received transpapillary endoscopic drainage for the cystic lesion with suspected walled-off necrosis. Thereafter, his symptoms improved. Conclusions The present case of MHT is the first to demonstrate acute necrotizing pancreatitis and it illustrates the difficulty of treatment. Therefore, if a patient with MHT presents with abdominal pain, a thorough workup, including contrast-enhanced computed tomography, should be performed to rule out significant organ involvement.

Ostre uszkodzenie nerek i mikroangiopatia zakrzepowa spowodowane nadciśnieniem złośliwym u 21-letniego pacjenta

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Alarming trends in the frequency of malignant hypertension among admissions with a known cannabis use disorder

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Apr 2021

Is headache at admission associated with higher rate of recent brain MRI injury during malignant hypertension crisis?

Article

Full-text available

Dec 2022

Reliable clinical signs associated with recent brain injuries during malignant hypertension crisis are lacking. In this single-center study we compared the prevalence of brain MRI injuries between fully asymptomatic patients and those with headache; we found no significant differences, suggesting that headache is not associated with recent brain injuries during malignant hypertension.

Neurologically asymptomatic patients frequently present cerebral injuries during malignant hypertension: a MRI study

Article

Aug 2021
J Hypertens

Background: Acute and diffuse microvascular damage characterizes malignant hypertension (MHT), the deadliest form of hypertension (HTN). Although its ophthalmological, renal and cardiological repercussions are well known, brain involvement is considered rare with few descriptions, although it is one of the main causes of death. We hypothesized that brain MRI abnormalities are common in MHT, even in patients without objective neurological signs. Method: We analyzed retrospectively the brain MRI of patients admitted for acute MHT between 2008 and 2018 in Bordeaux University Hospital, regardless of their neurological status. A trained operator analyzed every brain MRI, looking for posterior reversible encephalopathy syndrome (PRES), ischemic stroke, intracerebral hematoma (ICH) and microangiopathy markers. We included 58 patients without neurological signs, 66% were men, and mean age was 45.6 ± 11.3 years. Results: Brain MRI were normal in 26% of patients but we found at least one acute abnormality on brain MRI in 29% and an Small Vessel Disease score (SVD score) of two or higher in 52%. In patients with neurological signs, these findings were 9, 53 and 70%, respectively. A PRES was found in 16% of asymptomatic patients and 31% had an ischemic stroke and/or a cerebral hematoma. Conclusion: PRES, recent hematoma, ischemic stroke and severe cerebral microangiopathy are common findings in MHT patients without neurological signs on admission. The impact of these findings on patient management, and their cerebrovascular and cognitive prognostic value, should be established. Brain MRI might need to become systematic in patients suffering from MHT episodes.

Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura

Article

Full-text available

Jun 2015

Malignant hypertension can cause thrombotic microangiopathy (TMA) and the overall presentation may mimic thrombotic thrombocytopenic purpura (TTP). This presents a dilemma of whether or not to initiate plasma exchange. The objective of the study was to determine the clinical and laboratory manifestations of malignant hypertension-induced TMA, and its outcomes. Using several search terms, we reviewed English language articles on malignant hypertension-induced TMA, indexed in MEDLINE by 31 December 2013. We also report a new case. All these cases were analyzed using descriptive statistics. A total of 19 patients, with 10 males, had a median age of 38 years at diagnosis; 58% had a history of hypertension. Mean arterial pressure at presentation was 159 mmHg (range 123-190 mmHg). All had prominent renal dysfunction (mean creatinine of 5.2 mg/dl, range 1.7-13 mg/dl) but relatively modest thrombocytopenia (mean platelet count of 60 × 103/µl, range 12-131 × 10(3)/µl). Reported cases (n = 9) mostly had preserved ADAMTS-13 activity (mean 64%, range 18-96%). Following blood pressure control, the majority had improvement in presenting symptoms (100%) and platelet counts (84%); however, only 58% had significant improvement in creatinine. More than half (53%) needed hemodialysis. One patient died of cardiac arrest during pacemaker insertion. Prior history of hypertension, high mean arterial pressure, significant renal impairment but relatively modest thrombocytopenia and lack of severe ADAMTS-13 deficiency (activity <10%) at diagnosis are clues to diagnose malignant hypertension-induced TMA. Patients with malignant hypertension respond well to antihypertensive agents and have favorable nonrenal outcomes.

Malignant hypertension with thrombotic microangiopathy and persistent acute kidney injury (AKI)

Article

Full-text available

Dec 2014

Two cases of malignant hypertension presenting with acute kidney injury, thrombocytopenia and hemolytic anemia are presented. In both patients a prolonged duration of renal replacement therapy was required. The plasma levels of ADAMTS13 enzyme were not helpful in delineating the precise pathogenesis in both cases, as the decrements were not severe. We discuss the clinic-pathologic correlation of the biopsy findings and persistence of AKI.

Renal Nitric Oxide Synthase and Antioxidant Preservation in Cyp1a1-Ren-2 Transgenic Rats With Inducible Malignant Hypertension

Article

Full-text available

Jun 2013
Am J Hypertens

BACKGROUND Dietary administration of 0.30% indole-3-carbinol (I3C) to Cyp1a1-Ren2 transgenic rats (TGRs) generates angiotensin II (ANG II)-dependent malignant hypertension (HTN) and increased renal vascular resistance. However, TGRs with HTN maintain a normal or slightly reduced glomerular filtration rate. We tested the hypothesis that maintenance of renal function in hypertensive Cyp1a1-Ren2 TGRs is due to preservation of the intrarenal nitric oxide (NO) and antioxidant systems.METHODS Kidney cortex, kidney medulla, aortic endothelial (e) and neuronal (n) nitric oxide synthase (NOS), superoxide dismutases (SODs), and p22phox (nicotinamide adenine dinucleotide phosphate-oxidase subunit) protein abundances were measured along with kidney cortex total antioxidant capacity (TAC) and NOx. TGRs were fed a normal diet that contained 0.3% I3C or 0.3% I3C + candesartan (AT1 receptor antagonist; 25mg/L in drinking water) (n = 5-6 per group) for 10 days.RESULTSBlood pressure increased and body weight decreased in I3C-induced TGRs, while candesartan blunted these responses. Abundances of NOS, SOD, and p22phox as well as TAC were maintained in the kidney cortex of I3C-induced TGRs with and without candesartan, while kidney cortex NOx production increased in both groups. Kidney medulla eNOS and extracellular (EC) SOD decreased and nNOS were unchanged in both groups of I3C-induced TGRs. In addition, a compensatory increase occurred in kidney medulla Mn SOD in I3C-induced TGRs + candesartan. Aortic eNOS and nNOS∝ fell and p22phox and Mn SOD increased in hypertensive I3C-induced TGRs; all changes were reversed with candesartan.CONCLUSIONS The preservation of renal cortical NO and antioxidant capacity is associated with preserved renal function in Cyp1a1-Ren2 TGRs with ANG II-dependent malignant HTN. © American Journal of Hypertension, Ltd 2013. All rights reserved.

Central Versus Peripheral Blood Pressure in Malignant Hypertension; Effects of Antihypertensive Treatment

Article

Full-text available

Apr 2013
Am J Hypertens

Background: Sodium nitroprusside (SNP) and labetalol are recommended for the immediate treatment of malignant hypertension. Both are intravenous agents but have different effects on systemic hemodynamics, and may have differential effects on pulse-wave reflection and pulse-pressure amplification, with consequences for peripheral versus central blood pressures (BPs). Methods: We conducted a nonrandomized, open-label study of 8 patients treated with sodium nitroprusside (mean age (±SD), 44±14 years; 6 males; diastolic/systolic BP, 225±22/135±8mm Hg) and 6 patients treated with intravenous labetalol (mean age, 39±15 years; 4 males; systolic/diastolic BP, 232±22/138±17mm Hg) before and after treatment for malignant hypertension, aiming at a 25% reduction in mean arterial pressure. We measured peripheral pressures with an intra-arterial catheter in the radial artery and derived central pressures with a generalized transfer filter. Results: Mean arterial pressure was similarly reduced with sodium nitroprusside and labetalol (by 27% and 30%, respectively; P = 0.76). There was a nonsignificantly greater reduction in peripheral systolic blood pressure (SBP) with labetalol than with sodium nitroprusside (29±11% vs. 18±7%, P = 0.08). The decline in peripheral diastolic blood pressure (DBP) with the two agents was comparable, whereas the reduction in peripheral pulse pressure was 8±16% with SNP and 33±17% with labetalol (P = 0.01). The decline in reflection magnitude was greater with SNP than with labetalol. There were no significant differences in the reduction of central BP with SNP and labetalol. The amplification of PP increased with SNP but did not change with labetalol. Conclusions: We found no difference in central SBP or PP in subjects treated with SNP and labetalol, but labetalol produced a greater reduction in peripheral SBP and PP in the immediate treatment of malignant hypertension.

2013 ESH/ESC Guidelines for the management of arterial hypertension

Article

Jul 2013

Jennifer Taylor

The Angiotensin Type 1 Receptor Antagonist, Eprosartan, Attenuates the Progression of Renal Disease in Spontaneously Hypertensive Stroke-Prone Rats with Accelerated Hypertension

Article

Apr 2002

Christian T. Abrahamsen

The effects of the angiotensin type 1 (AT1) receptor antagonist, eprosartan, were studied in a model of severe, chronic hypertension. Treatment of male spontaneously hypertensive stroke prone rats (SHR-SP) fed a high-fat, high-salt diet with eprosartan (60 mg/kg/day i.p.) for 12 weeks resulted in a lowering of blood pressure (250 ± 9 versus 284 ± 8 mm Hg), renal expression of transforming growth factor-β mRNA (1.5 ± 0.2 versus 5.4 ± 1.4) and the matrix components: plasminogen activator inhibitor-1 (5.2 ± 1.4 versus 31.4 ± 10.7), fibronectin (2.2 ± 0.6 versus 8.2 ± 2.2), collagen I-α1 (5.6 ± 2.0 versus 23.8 ± 7.3), and collagen III (2.7 ± 0.9 versus 7.6 ± 2.1). Data were corrected for rpL32 mRNA expression and expressed relative to Wistar Kyoto (WKY) rats [=1.0]. Expression of fibronectin protein was also lowered by eprosartan (0.8 ± 0.1 versus 1.9 ± 0.5), relative to WKY rats. Eprosartan provided significant renoprotection to SHR-SP rats as measured by decreased proteinuria (22 ± 2 versus 127 ± 13 mg/day) and histological evidence of active renal damage (5 ± 2 versus 195 ± 6) and renal fibrosis (5.9 ± 0.7 versus 16.4 ± 1.9) in vehicle- versus eprosartan-treated rats, respectively. Our results demonstrated that AT1 receptor blockade with eprosartan can reduce blood pressure and preserve renal structure and function in this model of severe, chronic hypertension. These effects were accompanied by a decreased renal expression of transforming growth factor-β1, plasminogen activator inhibitor-1, and several other extracellular matrix proteins compared with vehicle-treated SHR-SP.

Increasing Trend in Admissions for Malignant Hypertension and Hypertensive Encephalopathy in the United States

Article

Mar 2015
Hypertension

Malignant hypertension and hypertensive encephalopathy are life-threating manifestations of hypertension. These syndromes primarily occur in patients with a history of poorly controlled hypertension. The purpose of this study was to investigate national trends in hospital admissions for malignant hypertension, hypertensive encephalopathy, and essential hypertension. This was a retrospective cohort study that used the Nationwide Inpatient Sample. We identified all hospitalizations between 2000 and 2011, during which a primary diagnosis of malignant hypertension (ICD 9 code: 401.0), hypertensive encephalopathy (ICD 9 code: 437.2), or essential hypertension (ICD 9 code: 401.9) was recorded. Time series models were estimated for malignant hypertension, hypertensive encephalopathy, essential hypertension and also for the combined series. A piecewise linear regression analyses was performed to investigate whether there were changes in the trends of these series. In addition, we also compared the characteristics of patients with these diagnoses. The estimated number of admissions for both malignant hypertension and hypertensive encephalopathy increased dramatically after 2007, whereas discharges for essential hypertension fell, and there was no change in trend for the combined series. Costs rose substantially for patients with these diagnoses after 2007, but mortality significantly fell for malignant hypertension and mortality for hypertensive encephalopathy did not change. The dramatic increase in the number of hospital admissions for hypertensive encephalopathy and malignant hypertension should have resulted in dramatic increases in morbidity, but it did not. The change is most likely related to changes in coding related to diagnostic-related groups that occurred in 2007. © 2015 American Heart Association, Inc.

Mortality and Cardiovascular Risk in Patients With a History of Malignant Hypertension: A Case-Control Study

Article

Dec 2013
J Clin Hypertens

The survival of patients with malignant hypertension (MHT) has considerably improved over the past decades. Data regarding the excess risk of mortality and the contribution of conventional cardiovascular risk factors are lacking. The authors retrospectively assessed cardiovascular risk factors and all-cause mortality in 120 patients with a history of MHT and compared them with 120 normotensive and 120 hypertensive age-, sex-, and ethnicity-matched controls. Total cholesterol, low-density lipoprotein cholesterol, and body mass index were lower in MHT patients compared with hypertensive controls, whereas blood pressure, high-density lipoprotein cholesterol, and smoking habit were similar. Median estimated glomerular filtration rate was lower in MHT patients compared with normotensive and hypertensive controls (both P<.01). The annual incidence of all-cause mortality per 100 patient-years was higher in MHT patients (2.6) compared with normotensive (0.2) and hypertensive (0.5) controls (both P<.01). Mortality of patients with a history of MHT remains high compared with normotensive and hypertensive controls. Patients with MHT had a more favorable cardiovascular risk profile compared with hypertensive controls but a higher prevalence of renal insufficiency.

Immunosenescent CD8(+) T Cells and C-X-C Chemokine Receptor Type 3 Chemokines Are Increased in Human Hypertension

Article

May 2013
Hypertension

The pathogenic role of T cells in hypertension has been documented well in recent animal studies. However, the existence of T-cell-driven inflammation in human hypertension has not been confirmed. Therefore, we undertook immunologic characterization of T cells from patients with hypertension and measured circulating levels of C-X-C chemokine receptor type 3 chemokines, which are well-known tissue-homing chemokines for T cells. We analyzed immunologic markers on T cells from patients with hypertension by multicolor flow cytometry. We then measured circulating levels of the C-X-C chemokine receptor type 3 chemokines, monokine induced by γ interferon (IFN), IFN γ-induced protein 10, and IFN-inducible T-cell α chemoattractant, in patients with hypertension and in age- and sex-matched control subjects by the cytometric bead array method. In addition, we examined histological features of IFN-inducible T-cell α chemoattractant expression from renal biopsy specimens of patients with hypertensive nephrosclerosis and control subjects. The total T-cell population from patients with hypertension showed an increased fraction of immunosenescent, proinflammatory, cytotoxic CD8(+) T cells. Circulating levels of C-X-C chemokine receptor type 3 chemokines were significantly higher in patients with hypertension than in control subjects. Furthermore, immunohistochemical staining revealed increased expression of the T-cell chemokine, IFN-inducible T-cell α chemoattractant, in the proximal and distal tubules of patients with hypertensive nephrosclerosis. Immunosenescent CD8(+) T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension, suggesting a role for T-cell-driven inflammation in hypertension. A more detailed characterization of CD8(+) T cells may offer new opportunities for the prevention and treatment of human hypertension.

Malignant Hypertension in Patients Treated With Vascular Endothelial Growth Factor Inhibitors

Article

Mar 2013
J Clin Hypertens

The development of drugs capable of modulatingangiogenesis has created a signiﬁcant improvement inthe survival associated with metastatic tumors. Thisgroup of drugs includes anti-vascular endothelialgrowth factor (VEGF) monoclonal antibodies (bev-acizumab), intracellular VEGF receptor inhibitors (so-rafenib, sutinib, pazopanib), and the small VEGFinactivating molecules (VEGF trap).