Malignant hypertension (MHT), the most severe form of hypertension, is a hypertensive emergency associated with severe blood pressure (BP) elevations as well as rapid onset and progression. Systemic microvascular damage is the pathological hallmark of MHT, affecting in particular the retina, brain, heart, and kidneys.1

Precise data on MHT incidence are scant, and the estimated prevalence of 2 new cases per 100 000 individuals per year was reported in 2 European cohorts from Birmingham (United Kingdom) and Amsterdam (the Netherlands). The rate is up to 4-fold higher (7.3 per 100 000 per year) in developing countries, particularly in Black African / Afro-Caribbean populations. Recent studies2 have indicated that the number of incident cases of MHT is not decreasing but rather growing across Europe and the United States.

Eye, cardiac, and kidney lesions related to MHT are reported in more than half of patients and have been well characterized. Brain damage resulting from MHT has received little attention so far, while neurologic disorders are reported to be the second most frequent cause of death in patients with this form of hypertension.3

Hypertensive encephalopathy, present in approximately 1 in every 10 patients, is among the most life-threatening clinical presentations, and is one of the causes of posterior reversible encephalopathy syndrome, characterized by systemic microcirculatory damage, autonomic failure, and focal intracerebral edema. A recent study1 has shown that posterior lesions indicative of cerebral edema are common even in neurologically asymptomatic patients, highlighting the emergency status of MHT and a high risk of death from cerebrovascular causes in this group of patients.

Retinal lesions associated with MHT are important signs of systemic vascular damage, and correlate with an increased risk of ischemic stroke and other cardiovascular complications. In patients with severe BP elevations, funduscopic examination may reveal grade 3 or 4 hypertensive retinopathy with disk edema in both eyes, flame-shaped hemorrhages, hard exudates, and cotton-wool spots. Elevated intracranial pressure causes optic nerve ischemia and disk swelling—the clinical picture includes papilledema with flame-shaped hemorrhages at the disk margin. Hypertensive optic neuropathy is a common and late finding in MHT.

MHT has a profound effect on the cardiovascular system, and patients with this form of hypertension tend to have more abnormalities in echocardiographic parameters than the non-MHT and normotensive controls.

Based on transthoracic echocardiography, changes in cardiac structure and function in patients with MHT include greater left ventricular (LV) mass and its severe hypertrophy, greater dimensions of the LV and left atrium, and lower LV ejection fraction, as compared with individuals with nonmalignant essential hypertension.

Few studies and single case reports employed global longitudinal strain assessment in patients with MHT and demonstrated reduced function of LV longitudinal fibers. Using cardiac magnetic resonance imaging, symmetric LV hypertrophy as well as myocardial fibrosis and edema were demonstrated.

MHT is frequently complicated by renal dysfunction, and some patients present with acute kidney failure requiring emergency dialysis. Available studies have shown that between half and two-thirds of patients with MHT have decreased kidney function and proteinuria at presentation. In most cases, this is secondary to MHT, with renal biopsy specimens typically showing ischemic glomerular changes and tubular necrosis. The degree of kidney failure is associated with the presence of thrombotic microangiopathy, which is reported in 15%–30% of individuals with MHT.

Although the survival rate after an MHT event has considerably improved owing to the progress in hypertension management, this form of hypertension is still associated with poor prognosis, and end-stage renal disease remains a significant cause of morbidity and mortality. The Bordeaux cohort study4 reported that after 4 years of follow-up, 18% of patients with MHT (age range, 40–50 years) either developed end-stage kidney disease, had a major cardiovascular event, or died. In the Amsterdam cohort,5 15% of the patients died and 24% needed kidney replacement therapy after a median follow-up of 67 months.

Despite the fact that MHT confers a very high risk of cardiovascular complications and death, it still remains poorly recognized, and the awareness of this entity among physicians is low. Therapeutic guidelines for the management of MHT remain empiric and are mostly based on expert consensus statements and data from a limited number of retrospective clinical trials.6 Also, the definition and diagnostic criteria have not substantially changed since 1929, and epidemiologic and prognostic knowledge is mainly based on data from single-center cohorts.

HAMA (hypertension arterielle maligne; malignant hypertension) is a prospective, multicenter, multidisciplinary, observational cohort study originally started in 2019. It involves 36 centers across France and 1 in Poland (Department of Hypertension, National Institute of Cardiology, Warsaw, Poland) with the aim to include 500 patients in 5 years, with 5 years of follow-up.7 The goals of the HAMA registry are to create the first prospective, multicenter database of patients with MHT, increase awareness among the medical community, and improve disease screening. The registry should provide data on the current epidemiology of MHT and help establish recommendations based on strong scientific evidence to improve management of patients with this most dramatic form of hypertension.