Determinants of mortality in hypertensive patients admitted with COVID-19: a single-centre retrospective study at a tertiary hospital in South Africa.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has significantly impacted global health, with successive outbreaks leading to substantial morbidity and mortality. Hypertension, a leading cause of cardiovascular disease globally, has been identified as a critical comorbidity in patients with severe COVID-19, exacerbating the risk of adverse outcomes. This study aimed to elucidate the impact of hypertension on COVID-19 outcomes within the South African context. METHODS: A retrospective analysis was conducted at King Edward VIII Hospital, KwaZulu-Natal, South Africa, encompassing patients aged 13 years and above admitted with laboratory-confirmed SARS-CoV-2 infection between June 2020 and December 2021. The study investigated the association between hypertension and COVID-19 outcomes, analysing demographic, clinical, and laboratory data. Statistical analysis involved univariate and multivariate logistic regression to identify predictors of mortality among the hypertensive cohort. RESULTS: The study included 420 participants-encompassing 205 with hypertension. Hypertensive patients demonstrated significantly greater requirements for oxygen and steroid therapy (p < 0.001), as well as higher mortality rates (44.88%, p < 0.001)) compared to their non-hypertensive counterparts. Key findings demonstrated that a lower oxygen saturation (adjusted odds ratio (aOR) 0.934, p = 0.006), higher pulse pressure (aOR 1.046, p = 0.021), elevated CRP (aOR 1.007, p = 0.004) and the necessity for mechanical ventilation (aOR 5.165, p = 0.004) were independent risk factors for mortality in hypertensive COVID-19 patients. Notably, the study highlighted the pronounced impact of hypertension-mediated organ damage (HMOD) on patient outcomes, with ischemic heart disease being significantly associated with increased mortality (aOR 8.712, p = 0.033). CONCLUSION: Hypertension significantly exacerbates the severity and mortality risk of COVID-19 in the South African setting, underscoring the need for early identification and targeted management of hypertensive patients. This study contributes to the understanding of the interplay between hypertension and COVID-19 outcomes, emphasising the importance of considering comorbidities in the management and treatment strategies for COVID-19. Enhanced pandemic preparedness and healthcare resource allocation are crucial to mitigate the compounded risk presented by these concurrent health crises.

Novel biomarkers in patients with uncontrolled hypertension with and without kidney damage.

INTRODUCTION: Estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR) are insensitive biomarkers for early detection of hypertension-mediated organ damage (HMOD). In this nationwide cross-sectional study, we assessed potential biomarkers for early HMOD in healthy persons and patients with hypertension. We hypothesised that plasma levels of biomarkers: (1) are different between healthy controls and patients with hypertension, (2): can classify patients with hypertension according to the degree of hypertension severity. DESIGN AND METHODS: Patients with hypertension prescribed ≥2 antihypertensive agents were selected from a multicentre study. Healthy controls were selected from an ongoing study of living kidney donor candidates. Uncontrolled hypertension was defined as systolic daytime ambulatory blood pressure ≥135 mmHg. Kidney HMOD was defined by ACR > 3.0 mg/mmol or eGFR < 60 mL/min/1.73 m2. Patients with hypertension were categorised into three groups: (1) controlled hypertension; (2) uncontrolled hypertension without kidney HMOD; (3) uncontrolled hypertension with kidney HMOD. Fifteen biomarkers were analysed using a Luminex bead-based immunoassay, and nine fell within the specified analytical range. RESULTS: Plasma levels of Interleukin 1 receptor antagonist (IL-1RA), neutrophil gelatinase-associated lipocalin (NGAL) and uromodulin were significantly different between healthy controls (n = 39) and patients with hypertension (n = 176). In regression models, with controlled hypertension (n = 55) as the reference category, none of the biomarkers were associated with uncontrolled hypertension without (n = 59) and with (n = 62) kidney HMOD. In models adjusted for cardiovascular risk factors and eGFR, osteopontin (OPN) was associated with uncontrolled hypertension without kidney HMOD (odds ratio (OR) 1.77 (1.05-2.98), p = 0.03), and regulated upon activation normal T-cell expressed and secreted (RANTES) with uncontrolled hypertension with kidney HMOD (OR 0.57 (0.34-0.95), p = 0.03). CONCLUSIONS: None of the biomarkers could differentiate our hypertension groups when established risk factors were considered. Plasma OPN may identify patients with uncontrolled hypertension at risk for kidney HMOD.

What is the context? In order to tailor individualised hypertension treatment, a risk assessment for cardiovascular disease (CVD) must be performed. This includes evaluation of established hypertension-mediated organ damage (HMOD), such as the presence of kidney damage and associated risk factors. Today, kidney function is assessed by blood and urine samples. However, today's blood and urine samples are not sensitive enough to capture kidney damage due to hypertension at a stage when prevention may be most effective.What is new? In this study, we evaluated plasma levels of biomarkers related to endothelial and kidney cell pathology, inflammation and fibrosis in healthy patients and patients with hypertension. We hypothesised that plasma levels of biomarkers could differentiate between different degrees of hypertension severity.Healthy controls had lower Interleukin 1 receptor antagonist (IL-1RA) and neutrophil gelatinase-associated lipocalin (NGAL) levels, but higher uromodulin compared to patients with hypertension. Except for osteopontin (OPN), all biomarkers showed significant trends in median biomarker levels across study groups. However, as hypertension severity increased, the median plasma OPN levels also rose. None of the biomarker could consistently differentiate the hypertension severity groups after considering established risk factors. However, OPN may be an early biomarker for kidney damage in hypertension.What is the impact? Biomarkers for early detection of organ damage in hypertension may guide targeted treatment. Plasma OPN may have potential to identify those at risk for hypertensive kidney damage. However, the studied biomarkers lack consistent discrimination across hypertension severity levels.

Subclinical Hypertension-Mediated Organ Damage (HMOD) in Hypertension: Atherosclerotic Cardiovascular Disease (ASCVD) and Calcium Score.

Calcium controls numerous events within the vessel wall. Permeability of the endothelium is calcium dependent, as are platelet activation and adhesion, vascular smooth muscle proliferation and migration, and synthesis of fibrous connective tissue. Double-helix computerized tomography is a noninvasive technique that can detect, measure, and compare coronary calcification in the coronary arteries. Despite some convincing evidence about the prognostic value and usefulness of coronary artery calcium score (CACS) in the stratification of cardiovascular risk in the high risk general population and also in hypertensive patients, current guidelines for the management of hypertension, do not include such evaluation among the recommended procedures to be performed in the majority of patients even with the intent to detect hypertension-mediated organ damage (HMOD) in an early phase. On the contrary, the European Society of Cardiology guidelines for the diagnosis and management of chronic coronary syndromes, the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, and the 2018 Cholesterol Clinical Practice Guidelines indicate that the evaluation of CACS may be of some usefulness in specific subpopulations, although this view is not accepted in the US Preventive Services Task Force document. Very recently, the European Society of Cardiology Guidelines on cardiovascular disease prevention in clinical practice stated that CACS estimation may be considered to improve risk classification around treatment decision thresholds. In conclusion, the use of CACS as a diagnostic tool is still controversial. While some evidence exists about is ability to improve stratification of cardiovascular risk in primary prevention, in particular in selected patients who are at intermediate or borderline risk of atherosclerotic cardiovascular disease, there is insufficient evidence to use it as a standard means to assess HMOD.