Potential treatment route for vascular dementia uncovered by UK researchers

14th August 2023

A potential therapeutic target underlying the cause of reduced cerebral blood flow to the brain that results in vascular dementia has been recently discovered by researchers at the University of Manchester.

Published in the journal Proceedings of the National Academy of Sciences, the study, which was carried out in mice, reveals that hypertension disrupts signalling within artery cells in the brain and leads to vascular dementia. To date, there is limited understanding of the cellular and molecular mechanisms by which elevated blood pressures give rise to changes in brain arteries.

The researchers used a blood pressure high (BPH/2) mouse model of hypertension. They studied pial arteries, which regulate the flow of blood across the brain surface through myogenic constriction.

Normally, vasodilatation within these arteries occurs through activation of large-conductance, calcium-activated potassium channels on the plasma membrane by nearby localised calcium-release events – referred to calcium sparks – from the sarcoplasmic reticulum (SR) of vascular smooth muscle cells.

In contrast, vasoconstriction occurs as a result of diminished activity of the calcium-activated potassium channels.

Vascular dementia in a mouse model

The researchers found that in the hypertensive mice, there was increased constriction of pial arteries, which suggested that the calcium sparks occurred normally. However, they also observed that the distance between the SR and the potassium channels was increased. Consequently, the calcium sparks failed to activate the potassium channels, preventing the normal vasodilatory response.

The net effect was increased constriction of arteries, reducing cerebral blood flow and behavioural alterations in the mice that approximated to deficits observed in human vascular dementia patients, including executive dysfunction, apathy and memory loss.

Professor Adam Greenstein, a clinician scientist specialising in high blood pressure at the University of Manchester and one of the leaders of the research, said: ‘By uncovering how high blood pressure causes arteries in the brain to remain constricted, our research reveals a new avenue for drug discovery that may help to find the first treatment for vascular dementia. Allowing blood to return as normal to damaged areas of the brain will be crucial to stopping this devastating condition in its tracks. 

‘Any drugs that are discovered to improve brain blood supply may also be able to open a new line of attack in treating Alzheimer’s disease, which causes very similar damage to blood vessels as vascular dementia. Drugs to restore healthy blood flow could make current treatments, which focus on removing harmful amyloid plaques in the brain, more effective.‘

Professor Sir Nilesh Samani, medical director at the British Heart Foundation, which funded the research, added: ‘Vascular dementia affects around 150,000 people in the UK, and this number is going up. There are no treatments to slow or stop the disease, but we know that high blood pressure is an important risk factor. The incurable symptoms are hugely distressing for patients and those close to them.   

‘This exciting research reveals a specific mechanism by which high blood pressure might increase the risk of vascular dementia. Pinpointing how arteries remain permanently narrowed in vascular dementia could lead to the development of new effective treatments, raising hope that there may soon be a way to prevent this illness from destroying more lives.‘

Novel approach to hypertension sees single injection of zilebesiran reduce blood pressure

24th July 2023

A single subcutaneous injection of zilebesiran, which inhibits hepatic angiotensinogen synthesis, maintained a reduced 24-hour ambulatory blood pressure for 24 weeks, an international research team has found.

If approved, the drug paves the way for a more convenient means of managing hypertension, which is normally treated with oral antihypertensive agents.

In the study, published in the New England Journal of Medicine, the research team, which included experts from the University of Edinburgh’s Centre for Cardiovascular Science, examined the value of zilebesiran – an investigational RNA interference therapeutic agent which inhibits hepatic angiotensinogen synthesis – as a treatment for hypertension.

The study consisted of five different parts (A to E) but the current analysis focused on only three: Parts A, B and E.

In Part A, patients with hypertension were randomised 2:1 to either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400 or 800 mg) or placebo and followed for 24 weeks. Part B focused on the effect of an 800 mg dose of zilebesiran on blood pressure under conditions of either a low- or high-salt diet. Finally, the team provided the results from Part E, which was an open-label study of a single fixed dose of zilebesiran in combination with daily irbesartan.

Zilebesiran and blood pressure control

Of the 107 patients enrolled, there were no reports of hypotension, hyperkalaemia or worsening of renal function that required medical intervention.

In Part A, patients who received zilebesiran had decreases in serum angiotensinogen levels that correlated with the administered dose after eight weeks (r = –0.56). Single doses of the drug exceeding 200 mg were associated with decreases in both systolic (>10 mm Hg) and diastolic blood pressure (>5 mm Hg) after only eight weeks and which were sustained after 24 weeks.

The findings from part B were consistent with attenuation of the effect on blood pressure by a high-salt diet. Similarly, patients in part E experienced a reduction in blood pressure with zilebesiran co-administration with irbesartan.

Professor David Webb, Christison chair of therapeutics and clinical pharmacology at the University of Edinburgh, who led the Edinburgh study site, said: ‘This is a potentially major development in hypertension. There has not been a new class of drug licensed for the treatment of high blood pressure in the last 17 years. This novel approach leads to a substantial reduction in blood pressure, both by day and night, that lasts for around six months after a single injection. This is attractive because it helps avoid the difficulty with adherence to treatment seen with current medicines. The next stage of clinical trials will focus on developing robust safety data, and broader evidence of efficacy, before zilebesiran can be licensed for use.‘

Moderate dietary salt restriction reduces BP in primary aldosteronism

14th April 2023

A moderate dietary reduction of salt intake gives rise to a significant reduction in blood pressure in those with primary aldosteronism

German researchers have observed significant reduction in blood pressure (BP) following a moderate dietary reduction of salt intake in patients with primary aldosteronism.

The link between intake of sodium (in the form of salt) and hypertension is widely recognised such that reducing dietary intake not only lowers BP but is also associated with a reduction in morbidity and mortality from cardiovascular diseases. The presence of primary aldosteronism (PA) is a common cause of secondary hypertension and associated with excess cardiovascular morbidities. In fact, having PA is associated with more end-organ damage and an excess cardiovascular morbidity, including heart failure, stroke, nonfatal myocardial infarction, and atrial fibrillation compared to primary hypertension. An unfortunate consequence for patients with PA is a decreased taste sensitivity for salt, favouring high sodium consumption. Given this relationship, the German researchers wondered if a moderate dietary reduction in salt in patients with PA could reduce blood pressure.

Researchers identified a group of PA patients already under treatment with anti-hypertensives from a national registry. Individuals were recruited for a dietary salt restriction over 12 weeks with structured nutritional training and consolidation by a mobile health app. Salt intake and adherence were monitored every 4 weeks using 24-h urinary sodium excretion.

Moderate dietary salt reduction and blood pressure

A total of 41 participants with a mean age of 50 years (52.2% female) were included in the analysis.

At the end of the study, dietary salt intake which was originally estimated from urinary excretion to be 9.1 g/day, fell to 5.2 g/day (p < 0.001). In addition, systolic blood pressure reduced from 130 at baseline to to 121 mm Hg (p < 0.001) and diastolic blood pressure from 84 to 81 mm Hg (p = 0.003).

In addition, participants noted a significant weight loss of 1.4 kg (p < 0.001), largely due to water loss and an improvement in pulse pressure, an indicator of arterial stiffness (p < 0.001). Interestingly, there were also improvements in depression scores (p = 0.008).

The authors concluded that moderate dietary salt restriction intake in patients with PA substantially reduces BP and depressive symptoms.

Citation
Schneider H et al. Moderate dietary salt restriction improves blood pressure and mental well-being in patients with primary aldosteronism: The salt CONNtrol trial. J Intern Med 2023

Long-term exposure to higher road traffic noise linked to increased risk of hypertension

3rd April 2023

Exposure to higher road traffic noise over time is linked to a higher incidence of hypertension particularly if there is higher air pollution

In a prospective study, Chinese and UK researchers have found that long-term exposure to high levels of road traffic noise (RTN), especially when levels of air pollution are also increased, is associated with an increased risk for the development of hypertension.

Hypertension is the leading cause of cardiovascular disease and premature death worldwide with one estimate suggesting that 349 million in high-income countries are affected by the condition. While modification of lifestyle factors such as a reduced intake of sodium, stopping smoking and increased physical activity are an integral part of the overall management strategy for the disease, it has become recognised that road traffic noise exposure is associated with increased risk of premature arteriosclerosis, coronary artery disease, and stroke. Moreover, the World Health Organisation (WHO) has suggested that there is high quality evidence linking road traffic road and ischaemic heart disease. However, while the WHO has found evidence linking noise from air, road, or rail traffic with hypertension, they considered the quality of the supportive evidence to be ‘very low’. Although some data indicates that exposure to RTN increases both systolic and diastolic blood pressure, it remains uncertain if exposure might actually cause hypertension.

In the current study, researchers examined information held in the UK Biobank to evaluate the association between long-term RTN exposure with incident primary hypertension. The RTN level was estimated with common noise assessment methods and the development of hypertension through linkage with medical records.

Road traffic noise and incident hypertension

A total of 246,447 individuals with mean age of 55 years (54.6%) were included in the analysis. Over a median follow-up period of 8.1 years, there were 21,140 cases of incident primary hypertension recorded.

In fully adjusted models for continuous exposure to RTN, there was 7% increase in newly diagnosed hypertension per 10 dB [A] increment in the mean weighted average 24-hour road traffic noise level (hazard ratio, HR = 1.07, 95% CI 1.02 – 1.13). Interestingly, exposure to the highest level of RTN (> 65 db[A]), and the highest levels of air pollution, based on both fine particles and nitrogen dioxide, posed the greatest risk for incident hypertension (HR = 1.22 for fine particles, HR = 1.18 for nitrogen dioxide).

The authors concluded that long-term exposure to road traffic noise was associated with an increased incidence of primary hypertension and that this effect was stronger in presence of higher air pollution.

Citation
Huang J et al. Road Traffic Noise and Incidence of Primary Hypertension: A Prospective Analysis in UK Biobank. JACC Adv 2023

Metomidate scan enables diagnosis of primary aldosteronism

21st January 2023

Metomidate computed tomography scanning was able to successfully identify primary aldosteronism and was non-inferior to adrenal vein sampling

Metomidate used as a PET radiotracer and in combination with high resolution computed tomography (CT) has been shown to be non-inferior to adrenal vein sampling (AVS), as a non-invasive means of detecting primary aldosteronism according to a study by a team of UK researchers.

Primary aldosteronism (PA) has been shown to be responsible for 5.9% of cases of hypertension and this figure increased to 11.8% in patients with stage 3 hypertension. PA can be surgically corrected when caused by unilateral aldosterone hyper-secretion for which the usual cause is an aldosterone-producing adenoma. Moreover, hypertension due to PA has a worse prognosis compared with blood pressure-matched essential hypertension. The use of AVS is recognised as the most reliable means of identifying whether aldosterone production is uni- or bilateral. Nevertheless, an alternative is the use of imaging modality, such as metomidate positron emission tomography computed tomography (MTO) and which, in one small study has been shown to both a sensitive and specific alternative to adrenal vein sampling. Nevertheless, with a limited evidence base to demonstrate the value of this imaging modality, in the present study, researchers set out to compare the accuracy of MTO and AVS at predicting the outcome following adrenalectomy in patients with PA and ultimately resolution of hypertension in these patients. Individuals with confirmed PA underwent both MTO and AVS and were commenced on spironolactone 50mg but which was increased to 100mg after two weeks. Both techniques were used to assess the probability of unilateral PA and where this was high, unilateral adrenalectomy was recommended, or medical management where it was not detected.

Metomidate scanning and the outcome following adrenalectomy

A total of 128 patients with a median age of 52 years (68% male) were included in the study.

The use of MTO graded 52% of patients with a high probability of unilateral PA compared with 45% following AVS, although overall, 67% of the entire cohort were scored as having a high probability of unilateral PA.

Following surgery, the accuracy of MTO at predicting clinical success was 65.4% compared to 61.5% for AVS. These differences did not reach the predefined inferiority statistical margin; in other words, MTO was not inferior to AVS. Only 23 of 78 patients undergoing surgery achieved blood pressure readings of below 135/85mmHg, although 12 individuals were able to stop antihypertensive treatment.

There were a total of 24 serious adverse events although none of these were considered to be related to the procedures, and 22 fully resolved.

The authors concluded that MTO was an effective non-invasive means to diagnose unilateral PA and could be used as an alternative to AVS.

Citation
Wu X et al. [¹¹C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial. Nat Med 2023

Is heart failure risk increased following COVID-19 infection?

18th January 2023

Incident heart failure risk is significantly increased after an acute COVID-19 infection and directly influenced by age and prior hypertension

Heart failure risk has been found to be significantly elevated within 9 months of an acute COVID-19 infection and directly related to both age and a previous history of hypertension, according to a systematic review and meta-analysis by Italian researchers.

Although COVID-19 is primarily a respiratory infection, myocardial injury is a significant pathogenic feature and associated with worse in-hospital outcomes. In fact, it has become recognised that in addition to acute COVID-19-related cardiac complications such as myocarditis or pericarditis, follow-up studies also suggest an increased incidence of arrhythmia, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension and diabetes mellitus. One condition which has not fully explored, although identified as a potential adverse sequelae following infection with COVID-19, is incident heart failure (HF) risk. In the present study, the Italian team undertook a systematic review and meta-analysis of all studies, either retrospective or prospective, published at any time up to September 1, 2022 and which reported on the mid/long-term risk (defined as > 4 months) of incident HF in COVID-19 recovered patients. The researchers set the pooled incidence of HF in recovered patients as the primary outcome and the secondary outcome was the risk of incident HF compared to contemporary control group patients, i.e., those without COVID-19 infection.

Heart failure risk following COVID-19 infection

The analysis identified only 5 relevant and retrospective studies. These studies involved 21,463,173 patients with mean age 54.5 years (58.7% males), of whom, 1,628,424 had confirmed COVID-19 infection while the remaining 19,834,749 represented the controls.

A random effect model revealed a pooled incidence of post COVID-19 HF in 1.1% of cases (95% CI 0.7 – 1.6). After a mean follow-up of 9.2 months, recovered COVID-19 patients had a significantly elevated incident heart failure risk (Hazard ratio, HR = 1.90, 95% CI 1.54 –3.24, p < 0.0001) in comparison to non-infected controls.

In addition, a meta-regression analysis showed a significant and direct relationship for the risk of incident HF using age (p  =  0.001) and a previous history of hypertension (p  =  0.02) as moderators. Interestingly, there was an indirect association observed when the follow-up length was adopted as moderating variable (p = 0.01), suggesting that this risk was higher in the early post-acute phase of the infection.

The authors concluded that COVID-19 survivors had an additional 90% risk of developing HF following infection, especially in the early post-acute phase of the infection.

Citation
Zuin M et al. Risk of incident heart failure after COVID-19 recovery: a systematic review and meta-analysis. Heart Fail Rev 2022

Higher lipoprotein A in hypertensives increases risk of adverse cardiovascular events

9th January 2023

Elevated lipoprotein A levels appear to have an important role in modifying the level of cardiovascular risk among patients with hypertension

Higher lipoprotein A levels among patients with hypertension, increase their risk of an adverse cardiovascular event according to the findings of a study by US researchers.

Lipoprotein A is a form of low-density lipoprotein (LDL) and an established, genetically determined risk factor for atherosclerosis, coronary artery disease, stroke, thrombosis, and aortic stenosis. It is synthesised in the liver and its plasma concentration ranges from < 1 mg to > 1,000 mg/dL although concentrations above 50 mg/dL are associated with an increased risk for cardiovascular disease including myocardial infarction, stroke, aortic valve stenosis, heart failure, peripheral arterial disease, and all-cause mortality. Levels are largely determined by genetics with up to 90% of the concentration explained by a single gene, the LPA gene. Moreover, concentrations above 50 mg/dL are observed in roughly 20% of the Caucasian population and in an even higher proportion of African-American and Asian-Indian people. It can therefore be assumed that Lp(a) is one of the most important genetically determined risk factors for cardiovascular disease.

Given this relationship with cardiovascular disease risk, in the current study, US researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) trial, to examine the longitudinal relationship of Lipoprotein A and hypertension to cardiovascular outcomes in a large multi-ethnic cohort, who were initially free of cardiovascular disease. MESA was designed to include patients from different ethnicities and aimed to include approximately 38% White, 28% African-American, 23% Hispanic and 11% Asian (of Chinese descent) individuals.

Among risk factors for cardiovascular disease, hypertension is associated with the strongest evidence for causation. As a result, in the current study, researchers categorised participants into four groups based on both lipoprotein A (Lp(a)) and the presence/absence of hypertension, which was defined by a systolic pressure of 140 mmHg or higher and a diastolic of 90 mmHg or the use of antihypertensive medicines. Group 1 had Lp(a) levels below <50 mg/dL and no hypertension; group 2 had Lp(a) levels ≥50 mg/dL but no hypertension; group 3 had Lp(a) <50 mg/dL and hypertension, whereas participants in group 4 had both an elevated Lp(a) (≥50 mg/dL) and hypertension. Individuals were then followed up until an adverse cardiovascular event.

Lipoprotein A levels, hypertension and adverse cardiovascular events

A total of 6,674 individuals with mean age of 62.1 years (52.8% female) and of whom, 38.6% were White, 27.5% Black, 22.1% Hispanic and 11.9% Chinese American, were followed for a mean of 13.9 years. During this time 809 participants experienced a cardiovascular disease event.

Using group 1 as the reference, those with Lp (a) ≥50 mg/dL and no hypertension (group 2) had no significant increased risk for cardiovascular disease events (Hazard ratio, HR = 1.09, 95% CI 0.79 – 1.50). In contrast, participants in group 3 (i.e., Lp(a) <50 mg/dL and hypertension) had a statistically significant increase in risk (HR = 1.66, 95% CI 1.39 – 1.98). The risk was also significantly elevated for those in group 4 (HR = 2.07, 95% CI 1.63 – 2.62).

In further analysis, the researchers identified that those with an elevated Lp(a) and with hypertension had an increased risk of cardiovascular disease events (HR = 1.24, 95% CI 1.01 – 1.53) relative to those with hypertension but lower Lp(a).

The authors concluded that while hypertension was a major contributor to cardiovascular risk, elevated Lp(a) significantly modified the association of hypertension with cardiovascular disease.

Citation
Rikhi R et al. Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA. Hypertension 2022

Baxdrostat effective in treatment-resistant hypertension

24th November 2022

Baxdrostat has been found to provide a significant reduction in systolic blood pressure in patients with treatment-resistant hypertension

Use of baxdrostat in patients with treatment-resistant hypertension, concurrently taking three other anti-hypertensives, led to significant reductions in systolic blood pressure compared to placebo according to the findings of a trial by UK and US researchers.

Hypertension is the leading preventable cause of premature death worldwide with one analysis of 90 countries estimated that globally, in 2010, 31.1% of the world’s adults had hypertension and which equated to 1.39 billion people. Despite the availability of a range of effective anti-hypertensive therapies, treatment-resistant hypertension, defined as above-goal elevated blood pressure in a patient despite the concurrent use of 3 antihypertensive drug classes, can be as high as 10.3%. One therapeutic target in hypertension is aldosterone synthase and a new class of drugs, the aldosterone synthase inhibitors, are currently under development. One such agent is baxdrostat and which has been shown in preclinical studies to completely suppress aldosterone production in humans without affecting cortisol production. Nevertheless, whether reducing aldosterone would also lower blood pressure was unclear and the subject of the current study.

Researchers focused on patients with treatment-resistant hypertension with a mean blood pressure of at least 130/80 mmHg, despite the use of three different anti-hypertensives. Participants were then randomised equally to 0.5, 1 or 2 mg of baxdrostat or matching placebo and were assessed for a period of 12 weeks. The primary efficacy endpoint was the change in the mean seated systolic blood pressure from baseline to the end of the study period. The change in diastolic pressure was then set as the secondary outcome measure.

Baxdrostat and changes in systolic blood pressure

A total of 248 patients with a mean age of 62.3 (55.8% male) were included and randomised to either placebo, 0.5, 1 and 2 mg of baxdrostat. The mean baseline systolic blood pressure ranged from 147.7 to 148.9 mmHg and the mean diastolic from 87.6 to 88.2 mmHg.

The change in systolic blood pressure at 12 weeks was significantly greater than placebo for the 2 mg dose (-20.3) and the mean difference compared to placebo was significant (p < 0.001). Similarly, the 1 mg dose achieved -17.5 reduction in systolic pressure and again the mean difference compared to placebo was significant (p = 0.003). There was no significant difference for the 0.5 mg dose.

The highest reduction in diastolic pressure occurred with the 2 mg dose (-14.3) and the 1 mg dose (-11.8) although no statistical significance data were reported.

The authors that there were reported no serious adverse events attributable to baxdrostat, and no instances of adrenocortical insufficiency.

They concluded that in patients with treatment-resistant hypertension, baxdrostat provided a dose-related reduction in blood pressure.

Citation
Freeman MW et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Eng J Med 2022

Risk of open angle glaucoma increased in hypertensives consuming the most salt

29th August 2022

The risk of open angle glaucoma is higher in hypertensives who use consume more dietary salt intake from either the table or through cooking

The risk of developing open angle glaucoma is significantly elevated in patients with hypertension who frequently add salt to their food either from the table or through cooking according to the findings of study by an international group of researchers.

Glaucoma is a multifactorial optic neuropathy characterised by the degeneration of retinal ganglion cells. The condition is associated with intra-ocular pressure-related damage to the optic nerve. Glaucoma is a leading cause of blindness and a 2017 analysis estimated that prevalence of blindness due to glaucoma worldwide was 75.6 per 100 000 in 2017.

The treatment of glaucoma is directed towards a lowering of the intra-ocular pressure in the eye through medication, laser surgery, incisional surgery or a combination of these. The two main types of glaucoma are open angle glaucoma (OAG) and closed angle glaucoma, although there at least 8 different additional types.

Furthermore, some research indicates a connection between OAG and blood pressure, although the findings are equivocal. For instance, one study found that hypertension, particularly if poorly controlled, appears to be related to a modest increased risk of OAG.

In contrast, another suggested that among patients with existing glaucoma, the nocturnal reduction in blood pressure might be an additional risk factor for such patients. A factor known to affect blood pressure is intake of sodium through salt and there is a good deal of evidence indicating that a reduction in dietary sodium (via salt) decreases both blood pressure and the incidence of hypertension.

But whether a greater intake of salt, particularly in those with existing hypertension, would also increase the the risk of OAG is unclear. As a result, in the present study, researchers examined the relationship between glaucoma and salt intake, among patients with hypertension and who were receiving anti-hypertensive treatment.

The researchers used data from the Thessaloniki Eye Study which was designed to examine the prevalence of open angle glaucoma in adults age 60 years and older. All study participants had in-clinic examinations which included blood pressure measurement and were interviewed about co-morbidities and lifestyle factors.

Participants were asked about salt intake and were categorised as ‘never users’, ‘rare/occasional’ (i.e., rare or occasional salt use at the table or during cooking) and ‘frequent users’ who normally added salt to food at the table and through cooking.

For the study, researchers considered the occurrence of any OAG, primary open angle glaucoma (POAG) and pseudo-exfoliation syndrome, regardless of whether these individuals also had glaucoma. Any OAG did include POAG even though the effect of salt intake was analysed separately for this form of glaucoma.

Open angle glaucoma and salt intake among hypertensives

The study included 1076 participants with a mean age of 80.5 years (48.1% female) of whom, 51.3% did not have OAG and 8.3% had any OAG.

Among the whole cohort, there was no association between the frequency of salt intake and any form of OAG. This was apparent for occasional vs never salt users (odds ratio, OR = 1.02, 95% CI 0.59 – 1.79, p = 0.93) and between often (or frequent) users vs never users (OR = 1.38, 95% CI 0.66 – 2.89, p = 0.39).

However, when the researchers looked at those with hypertension and currently taking treatment, there was a significant association for any type of OAG but only for the comparison of often vs never salt users (OR = 2.65, 95% CI 1.12 – 6.28, p = 0.03).

Using the same comparison, i.e. often vs never salt users, the relationship was also significant for POAG (OR = 3.59, 95% CI 1.16 – 11.11, p = 0.03). However, there were no significant effects from frequent salt intake among those with pseudo-exfoliation syndrome.

There was also a significant relationship between frequent use of salt and any OAG in patients with a diastolic blood pressure below 90 mmHg (OR = 2.42, 95% CI 1.0 – 5.84, p = 0.05).

Based on these findings, the authors concluded that frequent dietary salt intake may be associated with an increased prevalence of OAG in those currently taking anti-hypertensive drugs. They called for future studies to examine the pathophysiological changes to optic nerves vascular supply caused by salt load.

Citation
Tseng VL et al. Association Between Dietary Salt Intake and Open Angle Glaucoma in the Thessaloniki Eye Study J Glaucoma 2022

Hypertension remains a significant risk factor for severe COVID-19 in fully vaccinated

17th August 2022

The presence of hypertension still poses a significant risk factor for more severe disease in COVID-19, even among those fully vaccinated

Patients with hypertension even after receipt of three COVID-19 vaccination doses, remain at an elevated risk of severe breakthrough infections with the Omicron variant according to researchers from the Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, US.

Although full vaccination against COVID-19 initially required individuals to have two doses, the fact that immunity appears to wane over time has led to a recommendation for a third dose. In fact, a third dose appears to provide greater protection with data showing how a third dose of the BNT162b2 vaccine administered a median of 10.8 months after the second dose provided 95.3% efficacy against COVID-19 compared with two doses.

As more information emerged during the pandemic, it became clear that there were several important risk factors associated with the development of more severe illness and hypertensive patients were found to be more vulnerable to the development of serious complications.

However, several unanswered questions remained. For example, do the same risk factors apply with COVID-19 variants and does full vaccination mitigate these risk factors? These were the questions raised in the present, retrospective analysis by the US team.

The researchers examined a cohort of adults with at least three doses of the COVID-19 vaccine but who subsequently developed a breakthrough infection with the Omicron variant (confirmed by nasopharyngeal swabs and PCR testing) and were hospitalised at their centre.

The team collected demographic and co-morbidity data and used multivariable logistic regression analysis to assess the association between various factors such as age, comorbid conditions and the risk of hospitalisation and these covariates were adjusted for in the final analysis.

Hypertension and risk of severe illness

The researchers identified a total of 912 patients with a mean age of 56 years (41% male) of whom 15.9% were subsequently hospitalised with a breakthrough Omicron infection. Among the overall cohort, 27% were obese, 21% had diabetes and 54% were hypertensive and there was a mean of 72 days between vaccination and infection.

In regression analysis, the presence of hypertension was associated with a more than two-fold higher odds of being hospitalised, after adjustment for covariates (odds ratio, OR = 2.29, 95% CI 1.24 – 4.32). Other related elevated risk factors included the presence of a previous myocardial infarction (OR = 2.21, 95% CI 1.29 – 3.77).

Because hypertension is common in patients with a prior myocardial infarction, heart failure and chronic kidney disease, in a further analysis, the authors excluded patients with these three comorbidities. However, the elevated risk of hospitalisation in those with hypertension remained significant (OR = 2.54, 95% CI 1.32 – 5.37).

The authors concluded that the presence of hypertension remains an important risk factor for breakthrough COVID-19 infections even after full vaccination and that further research is required to understand the relationship between this risk factor to enable the development of mitigation strategies.

Citation
Ebinger J et al. Hypertension and Excess Risk for Severe COVID-19 Illness Despite Booster Vaccination Hypertension 2022