Latest Research in HTN

Antihypertensive drugs

Sameh Emil Sadek, MD
Professor of Cardiology
Military Medical Academy

ِApril 2024

Lasix for the prevention of de novo postpartum hypertension: A randomized placebo-controlled trial (LAPP Trial)

Ukachi N Emeruwa , Hooman Azad , Samsiya Ona , Shai Bejerano , et al.

PMID: 38641089                          DOI: 10.1016/j.ajog.2024.04.016


Background: Birthing people with de novo postpartum hypertensive disorders remain among the highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit to oral loop-diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension OBJECTIVE: To evaluate whether oral furosemide can reduce risk for de novo postpartum hypertension (dnPPHTN) among high-risk birthing people by reducing post-delivery blood pressure. Study design: From October 2021 to April 2022, we conducted a randomized triplemasked placebo-controlled clinical trial of individuals at high risk for dnPPHTN at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high-risk for the development of dnPPHTN based on a prespecified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a five-day course of oral furosemide 20 mg daily or identical-appearing placebo starting within eight hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was the difference in mean arterial pressure (MAP) averaged over the 24 hours prior to discharge or the 24 hours prior to antihypertensive therapy initiation. The study was powered to detect a 5 mmHg difference in mean MAP (standard deviation 6.4 mmHg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of dnPPHTN, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. Results: The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between groups. There was no significant difference in mean MAP 24 hours prior to discharge (or antihypertensive initiation) in the furosemide group (88.9 ± 7.4 mmHg) compared to the placebo group (86.8 ± 7.1 mmHg; absolute difference 2.1 mmHg, 95% CI -1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed dnPPHTN and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between groups. Conclusions: De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces mean MAP in the 24 hours prior to discharge from the delivery hospitalization (or antihypertensive medication initiation) compared to placebo. Keywords: antihypertensive therapy; healthcare innovation innovative technology; maternal health; maternal morbidity; neonatal outcomes; novel monitoring; oral furosemide; postpartum care; preventive therapies; remote monitoring technology; risk factor algorithm.

Jan 2024

Alzheimers Dement. 2022 Nov;18(11):2308-2326. doi: 10.1002/alz.12707. Epub 2022 Jun 27.


Hypertension and Alzheimer’s disease pathology at autopsy: A systematic review


Herrer Abdulrahman 1 2, Jan Willem van Dalen 1 2, Melina den Brok 1 2, Caitlin S Latimer 3, Eric

B Larson 4, Edo Richard 2 5




Hypertension is an important risk factor for Alzheimer’s disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be associated with AD neuropathological changes (ADNC), but reports are sparse and inconsistent. This systematic review included 15 autopsy studies (n = 5879) from observational cohorts. Studies were highly heterogeneous regarding populations, follow-up duration, hypertension operationalization, neuropathological methods, and statistical analyses. Hypertension seems associated with higher plaque and tangle burden, but results are inconsistent. Four studies (n = 3993/5879; 68%), reported clear associations between hypertension and ADNC. Another four suggested that antihypertensive medication may protect against ADNC. Larger studies with longer follow-up reported the strongest relationships. Our findings suggest a positive association between hypertension and ADNC, but effects may be modest, and possibly attenuate with higher hypertension age and antihypertensive medication use. Investigating interactions among plaques, tangles, cerebrovascular pathology, and dementia may be key in better understanding hypertension’s role in dementia development.

Keywords: Alzheimer’s disease; blood pressure; hypertension; neuritic plaques; neurofibrillary tangles; neuropathology; systematic review.


Curr              Opin              Nephrol              Hypertens. 2023              Mar              1;32(2):111- 117. doi:10.1097/MNH.0000000000000862.


Targeting              inflammation              in hypertension


Andreas Deussen 1, Irakli Kopaliani




Purpose of review: Hypertension remains a global health and socioeconomic burden. Immune mechanisms are now recognized as integral part of the multifactorial etiology of hypertension and related organ damage. The present review addresses inflammatory pathways and immune targets in hypertension, which may be important for an immunomodulatory treatment of hypertension aside from lowering arterial pressure.

Recent findings: Anti-inflammatory interventions targeting single interleukins or almost the entire immune system show different beneficial effects. While immunomodulation (targeting specific portion of immune system) shows beneficial outcomes in certain groups of hypertensives, this does not pertain to immunosuppression (targeting entire immune system). Immunomodulatory interventions improve outcomes of hypertension independent of arterial pressure. The studies reveal interleukins, such as interleukin (IL)-1β and IL-17 as targets of immunomodulation. Besides interleukins, targeting αvβ-3 integrin and matrix metalloproteinase-2 or using experimental cell-therapy demonstrate beneficial effects in hypertensive organ damage. The NLR family pyrin domain containing 3 (NLRP3) inflammasome/IL-1β/endothelial cell/T-cell axis seems to be an important mediator in sustained inflammation during hypertension.

Summary: Although immunomodulation may be advantageous as a causal therapy in hypertension, targeting immune networks rather than single interleukins appears of major importance. Further research is required to better identify these networks and their links to human hypertension.


J Hum Hypertens. 2023 Oct;37(10):863-879. doi: 10.1038/s41371-022-00776-9. Epub 2022

Nov 22.


Management of hypertensive crisis: British and Irish Hypertension Society Position document


Spoorthy Kulkarni 1, Mark Glover 2, Vikas Kapil 3 4, S M L Abrams 5, Sarah Partridge 6, Terry

McCormack 7, Peter Sever 8, Christian Delles 9, Ian B Wilkinson 10

Affiliations expand






Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating anti- hypertensive therapy and setting BP goal in acute settings requires important considerations which differ slightly across various diagnoses and clinical contexts. This position paper by British and Irish Hypertension Society, aims to provide clinicians a framework for diagnosing, evaluating, and managing patients with hypertensive crisis, based on the critical appraisal of available evidence and expert opinion.



Follow link to download free pdf


Intern Med J. 2023 Oct;53(10):1739-1751. doi: 10.1111/imj.16189. Epub 2023 Jul 26.


Revisiting resistant hypertension: a comprehensive review


Ryan J Chan 1, Wryan Helmeczi 2, Swapnil S Hiremath 1 3


  • PMID: 37493367



Resistant hypertension (RHT) is typically defined as blood pressure that remains above guideline-directed targets despite the use of three anti-hypertensives, usually including a diuretic, at optimal or maximally tolerated doses. It is generally estimated to affect 10-30% of those diagnosed with hypertension, though the true incidence might be lower after one factor in the prevalence of non-adherence. Risk factors for its development include diabetes, obesity and other adverse lifestyle factors, and a diagnosis of RHT confers a greater risk of adverse cardiovascular outcomes, such as stroke, heart failure and mortality. It is essential to exclude pseudoresistance and secondary hypertension and to ensure non-pharmacologic management is optimised prior to consideration of fourth-line anti-hypertensive agents or advanced interventions, such as device therapies. In this review, we will cover the different definitions of RHT, along with the importance of careful diagnosis and management strategies, and discuss newer agents and research needs.

Keywords: adherence; blood pressure; hypertension; pharmacotherapy; resistant hypertension.

High Salt Intake Linked to Atherosclerosis

Even With Normal BP



A large study from Sweden concludes that a high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension. The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.


It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined. The analysis included 10,788 adults ages 50 to 64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake. CCTA was used to obtain 3D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.


After adjusting for age, sex, and study, the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries. Each 1000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio [OR], 1.09; < .001; confidence interval [CI], 1.06 – 1.12), a higher coronary artery calcium score (OR, 1.16; < .001; CI, 1.12 – 1.19), and a 17% increased occurrence of coronary artery

stenosis (OR, 1.17; < .001; CI, 1.13 – 1.20).







Eur Heart J Open. Published online March 30.


Diabetes Drug Tied to Lower Dementia



New research suggests that treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease,


A large cohort study from Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug. However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.


Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period. Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers. There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.75 – 0.95).


A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55 – 0.94).





The results were published in Neurology.


Scientific Advances and Dietary Measures

to Slow Down Aging


Spectacular progress is being made in slowing down aging, with three new molecular indicators of measurable and manageable processes that accelerate or slow down deterioration associated with age, as well as age-related pathologies. These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.


An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.


A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.


The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component. Eating nuts (eg, almonds, walnuts) is associated with a less dyslipidemia. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.


At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging.


Irregular Sleep Tied to Markers of



A new report suggests that irregular sleep such as inconsistent sleep duration or sleep timing may increase the risk of developing atherosclerosis among adults older than age 45. In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.


Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes. Authors found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night. The study was published recently in the Journal of the American Heart Association.


Data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) Sleep Ancillary Study, which included adults between the ages of 45 and 84 years in six US communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013 was examined.


For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.


The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.


Those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39 [95% CI, 1.07 – 1.82]) in comparison with those with more regular sleep timing (SD < 30 minutes).


J Am Heart Assoc. Published online February 15, 2023.


Extra Dietary Sodium Restrictions May Not

Lead to Better Outcomes


Restricting dietary sodium below recommended levels may not be helpful and was linked to an increase in in-hospital mortality, according to research presented at the last annual meeting of the American College of Cardiology together with the World Congress of Cardiology.


U.S. Dietary Guidelines for Americans recommend a dietary sodium intake of

2.3 g/day or less for most adults. The current meta-analysis of randomized trials showed that, in patients with heart failure, sodium restriction resulted in increased mortality. In the absence of benefit of salt restriction and [given the] increased harm, there should be a reconsideration of such recommendation.


Limiting sodium is still the way to go to help manage heart failure, but the amount of restriction has been up for debate . The study showed that the focus should be on establishing a safe level of sodium consumption instead of overly restricting sodium.


A possible explanation for these results could be activation of downstream antidiuretic and antinatriuretic systems. In addition, sodium improves the taste of food exponentially and its restriction may reduce the overall intake of total calories and required nutrients, which may lead to worse nutritional status.

EuroIntervention2023 Feb 15;EIJ-D-22-00723. doi: 10.4244/EIJ-D-22-00723. Online ahead of print.


Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Emanuele Barbato Michel Azizi Roland E Schmieder , et al.


PMID: 36789560.



Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood

pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice.

This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision- making process should take (i) the patient’s global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure.

Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.


Clin Hypertens2023 Feb 15;29(1):11. doi: 10.1186/s40885-023-00234-9.


The 2022 focused update of the 2018 Korean Hypertension Society Guidelines for the management of hypertension

Hack-Lyoung Kim Eun Mi Lee Shin Young Ahn , et al.


PMID: 36788612



Hypertension is the leading cause of death in human being, which shows high prevalence and associated complications that increase the mortality and morbidity. Controlling blood pressure (BP) is very important because it is well known that lowering high BP effectively improves patients’ prognosis. This review aims to provide a focused update of the 2018 Korean Hypertension Society Guidelines for the management of hypertension. The importance of ambulatory BP and home BP monitoring was further emphasized not only for the diagnosis but also for treatment target. By adopting corresponding BPs, the updated guideline recommended out-of- office BP targets for both standard and intensive treatment. Based on the consensus on corresponding BPs and Systolic Blood Pressure Intervention Trial (SPRINT) revisit, the updated guidelines recommended target BP in high-risk patients below 130/80 mmHg and it applies to hypertensive patients with three or more additional cardiovascular risk factors, one or more risk factors with diabetes, or hypertensive patients with subclinical organ damages, coronary or vascular diseases, heart failure, chronic kidney disease with proteinuria, and cerebral lacunar infarction. Cerebral infarction and chronic kidney disease are also high-risk factors for cardiovascular disease. However, due to lack of evidence, the target BP was generally determined at

< 140/90 mmHg in patients with those conditions as well as in the elderly. Updated contents regarding the management of hypertension in special situations are also discussed.

Keywords: Blood pressure; Guideline; Hypertension; Korea.


Diabetes Metab Syndr Obes. 2023 Feb 8;16:345-363. doi: 10.2147/DMSO.S396011. eCollection 2023.


Association Between Hypertension and New-Onset Non-Alcoholic Fatty Liver Disease in Chinese Non-Obese People: A Longitudinal Cohort Study

Dezhi Yang Jing Lan Ji Cen Yong Han, Haofei Hu


PMID: 36788988.



Background: Quantification of the relationship between hypertension and non- alcoholic fatty liver disease (NAFLD) risk is limited and controversial. This study aimed to investigate the relationship between hypertension and NAFLD in non-obese Chinese and to use different methods to demonstrate that hypertension is an independent risk factor for NAFLD.

Methods: On 16,153 nonobese individuals, a retrospective cohort study was conducted in China to examine the impact of hypertension on incident NAFLD. We compared five methods: multivariable Cox proportional-hazards regression, propensity score-matched (PSM) analysis, propensity score adjustment method (considering the propensity score as a covariate in a multivariable Cox proportional- hazard regression), and two propensity score-based weighted methods-The first one estimated the hypertension effect in the overall study population-inverse probability of treatment weights (IPTW), the other in the hypertensive population-standardized mortality ratio (SMR) weights. We also used a genetic matching (GenMatch) algorithm to match the participants for sensitive analysis.

Results: Between 2010 and 2014, 16,153 participants met our inclusion criteria, including 2427 (15.03%) with hypertension. A total of 2321 (14.37%) participants developed NAFLD during the median follow-up of 2.98 years. The crude hazard ratio (HR) between hypertension and incident NAFLD was 2.05 (95% confidence interval (CI): 1.87, 2.25). The adjusted HR depended on the different methods, ranging from 1.09 (95% CI: 0.77, 1.23) for the PSM method to 2.24 (95% CI: 2.05, 2.44) for the SMR

weighted analysis. Hypertensive participants with high propensity scores had a higher risk of developing NAFLD in the future. Excluding participants with propensity scores <8% yielded comparable hazard ratios with a narrower range, from 1.04 to


1.80. After adjusting for the confounding variables, the relationship also existed in the GenMatch cohort as a sensitivity analysis (HR=1.06, 95% CI 1.01-1.13).

Conclusion: Hypertension is a significant cause of NAFLD in Chinese adults in non- obese Chinese adults, with the hazard ratio ranging from 1.09 to 2.24.

Keywords: hypertension; inverse probability of treatment weights; non-alcoholic fatty liver disease; propensity-score matching; standardized-mortality-ratio weights.


BMC Cardiovasc Disord2023 Feb 14;23(1):87. doi: 10.1186/s12872-023-03114-0.


The effect of combining therapeutic drug monitoring of antihypertensive drugs with personalised feedback on adherence and resistant hypertension: the (RHYME-RCT) trial protocol of a multi-centre randomised controlled trial

L E J Peeters M H W Kappers, E Boersma, E K Massey, et al.


PMID: 36788491



Background: Adherence to antihypertensive drugs (AHDs) is important for adequate blood pressure control. Not taking these drugs as prescribed is one of the main underlying causes for resistant hypertension (RH), which in turn leads to an increased risk of cardiovascular events, stroke and kidney damage. Therefore, correct identification of patients that are non-adherent to AHDs is crucial to improve clinical outcome. For this goal, therapeutic drug monitoring is the most reliable method. The primary objective of this trial is to investigate whether monitoring of drug concentrations with a dried blood spot (DBS) sampling method combined with personalised feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Secondary objectives include the difference over time in the number of required AHDs as well as the defined daily dose (DDD). Lastly, the cost-utility of SoC versus the intervention in RH is determined.

Methods: This is a multi-centre single-blinded randomised controlled trial (RHYME- RCT). First, at an eligibility visit, DBS sampling, to monitor drug concentrations in blood, and a 24-h ambulatory blood pressure measurement (24-h ABPM) are performed simultaneously. Patients with a daytime systolic blood pressure (SBP) > 135 and/or diastolic blood pressure (DBP) > 85 mmHg are randomised to SoC or intervention + SoC. The intervention is performed by the treating physician and includes information on drug concentrations and a comprehensive personalised feedback conversation with the use of a communication tool. The follow-up period is one year with visits at 3, 6 and 12 months randomisation and includes 24-h ABPM and DBS sampling.


Discussion: This will be the first trial that focusses specifically on patients with RH without taking into account suspicion of non-adherence and it combines monitoring of AHD concentrations to identify non-adherence to AHDs with a comprehensive feedback to improve non-adherence. Furthermore, if this trial shows positive outcomes for the intervention it can be directly implemented in clinical practice, which would be a great improvement in the treatment of RH.

Trial registration: RHYME-RCT is registered in the Dutch Trial Register on 27/12/2017 (NTR6914) and can be found in the International Clinical Trials Registry Platform.

Keywords: Adherence; Antihypertensive drugs; Blood pressure; Hypertension; Intervention; Therapeutic drug monitoring.

Test Lp(a) Levels to Inform ASCVD Management


Lipoprotein (a) levels should be measured in clinical practice to refine risk prediction for
atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if
they cannot yet be lowered directly, recommends the National Lipid Association (NLA)
in a scientific statement.

The statement was published in the Journal of Clinical Lipidology on August 2022.

The question in the scientific community is: What role does that particular biomarker
play in terms of causing serious heart disease, stroke, and calcification of the aortic
valve? It actually can contribute and or cause any of those conditions. This has been
confirmed in meta-analyses of prospective, population-based studies showing a high risk
for MI, coronary heart disease, and ischemic stroke with high Lp (a) levels.

The thing that’s then sort of problematic is that we don’t have a specific treatment
to lower” Lp (a). There are nevertheless several drugs in phase 2 and 3 clinical trials that
appear to have the potential to significantly lower Lp (a) levels. Increased Lp (a) levels
are recognized as being on a continuum in terms of their risk, such that there is no level at
which raised concentrations can be deemed safe.

J Clin Lipidol. Published online August 2022


Artificial Sweeteners Linked to Higher CV Event Risk


Health concerns about the consumption of artificial sweeteners could be strengthened
with the publication of a new study linking their intake to increased risk of heart disease
and stroke events. In this latest large-scale, prospective study of French adults, total
artificial sweetener intake from all sources was associated with increased risk overall of
cardiovascular and cerebrovascular disease.

The study was published in the BMJ on September 2022.

The current study differs from those done previously in that it includes artificial
sweetener intake from both food and drinks, whereas previous studies have focused
mainly on artificial sweetener content of beverages alone. Just over half of the artificial
sweetener intake in the study came from drinks, with the rest coming from tabletop
sweeteners and foods.

There is mounting evidence correlating artificial sweeteners to weight gain and heart
disease. The advice would be that we all need to try to limit sugar intake, but we should
not consider artificial sweeteners as safe alternatives. Rather, we need to try to reduce our
need for a sugary taste in our diet.

Risk Increased by 9%

The current study included 103,388 French adults from the NutriNet-Sante cohort, of
whom 37.1% reported consumption of artificial sweeteners. The sweeteners assessed
were mainly aspartame (58% of sweetener intake), acesulfame potassium (29%), and
sucralose (10%), with the other 3% made up of various other sweeteners including
cyclamates and saccharin. Results showed that over an average 9 years follow up,
artificial sweetener intake was associated with a 9% increased risk of cardiovascular or
cerebrovascular events, including myocardial infarction, acute coronary syndrome,
angioplasty, angina, stroke, or transient ischemic attack, with a hazard ratio of 1.09 (95%
CI, 1.01 to 1.18; P = .03).
          The average intake of artificial sweeteners among those who reported consuming
them was 42.46 mg/day, which corresponds to approximately one individual packet of
tabletop sweetener or 100 mL of diet soda.

Going to Medical Conferences Has Similar
COVID Risk to Staying Home: Study

As COVID rates continue to decline globally and across the United States, many
professional healthcare associations are gradually resuming in-person meetings. This is despite the increasing number of online meetings and the shift in dynamics from physical sessions to virtual conferences during COVID lockdown restrictions.

            Although few studies have found that COVID case numbers are high after general
mass meetings, information on viral transmission rates after such in-person meetings are
often limited, unpublished, and unreliable — at best.

A study published September 2022 in JAMA Network Open compared COVID  rates among in-person attendees and virtual attendees of the Academic Surgical Congress  — the largest surgical society meetings in the United States. The conference, which was
held in Orlando, Florida, on February 1, shortly after the peak of the Omicron wave, gave participants the option of in-person or virtual attendance.

This study is the first to assess COVID-19 rates after a large in-person meeting of healthcare workers. There have been anecdotal reports of transmission at other meetings but no large-scale evaluations of risk of transmission with attendance at a medical
conference. Clarke’s team recruited registrants for a survey assessment of COVID testing and symptoms 7 days after the meeting. The researchers collated data from anonymous surveys and evaluated differences in positivity rates between virtual and in-person attendees.

During the meeting, steps to prevent COVID transmission included encouraging  self-testing, mandatory vaccination and masking, and the serving of food and beverages outdoors.

Concerning the efficacy of COVID-specific measures, It is difficult to prove that the measures were effective at reducing transmission because authors don’t know what the rates would have been if the measures were not in place. However, the data is suggestive that the evidenced-based preventative measures implemented by the meeting organizers were effective at keeping transmission rates low, and in-person attendance at the conference did not increase the risk of contracting COVID.

A recent study published in the Scientific Reports journal just 2 days ago revealedthat hypertension was not a predictor of perioperative cardiac arrest. This finding is surprizing and totally unexpected. Read the whole article for more data. 

Sci Rep. 2022 Aug 12;12(1):13709. doi: 10.1038/s41598-022-17916-3.

A retrospective study of mortality for perioperative cardiac arrests toward a personalized treatment

Huijie Shang 1 2 , injun Chu 3, Muhuo Ji , Jin Guo 1, Haotian e , Shasha Zheng 5, ianjun Yang 6


Perioperative cardiac arrest (POCA) is associated with a high mortality rate. This work aimed  o study   s prognostic factors   r risk mitigation by   ans of care     nagementand  lanning. A database of  380,919 surgeries was reviewed, and 150 POCAs were curated. The main outcome was mortality prior to hospital discharge. Patient  demographic, medical history, and clinical characteristics (anesthesia and surgery)
were the main features. Six machine learning (ML) algorithms, including LR, SVC, RF, GBM, AdaBoost, and VotingClassifier, were explored. The last algorithm was an  ensemble of the first five algorithms. k-fold cross-validation and bootstrapping minimized the prediction bias and variance, respectively. Explainers (SHAP and LIME) were used to interpret the predictions. The ensemble provided the most accurate and
robust predictions (AUC = 0.90 [95% CI, 0.78-0.98]) across various age groups. The risk factors were identified by order of importance. Surprisingly, the comorbidity of hypertension was found to have a protective effect on survival, which was reported by a recent study for the first time to our knowledge. The validated ensemble classifier in aid of the explainers improved the predictive differentiation, thereby deepening our understanding of POCA prognostication. It offers a holistic model-based approach for personalized anesthesia and surgical treatment.

Modified Snacks Reduce LDL Cholesterol

A new, randomized crossover study shows that individuals who ate specifically formulated snacks high in certain ingredients including fiber, phytosterols, and antioxidants reduced their LDL cholesterol, even in the absence of other dietary or lifestyle changes.
           Investigators randomized 54 adults to receive either the specially formulated snacks made by Step One Foods or control snacks from the grocery store that were similar in calories and packaging.
Participants were instructed to consume the snacks twice a day as a substitute for something they were already eating and to make no other changes in diet or lifestyle. None of the patients were receiving statin drugs either before or during the study period.
           After the first 4 weeks, a 4-week washout period ensued, and then the original control group crossed over to receive the specially formulated snacks, while the experimental group now received the control snacks.
           LDL cholesterol levels fell by almost 9% and total cholesterol (TC) by 5% in those receiving treatment foods compared with those receiving control foods.

          Authors noted that what you eat is very important, and you can eat foods that will lower your cholesterol. Based on their study findings, this type of ‘food-as-medicine’ approach expands the options for medical professionals and patients, as many patients are either unwilling or unable to take statins drugs and may be able to manage their hyperlipidemia with realistic food-based interventions.


The study was published online January 2022 in The Journal of Nutrition


Current ‘Safe’ Alcohol Consumption Levels Potentially Harmful

A new research, published in Clinical Nutrition , suggests that even following the current alcohol consumption guidance             

    from the UK’s Chief Medical Officers – which advises: “To keep health risks from alcohol to a low level, both men and women are advised not to regularly drink more than 14 units a week” – will potentially increase a person’s risk of fatal and non-fatal cardiovascular events, ischemic heart disease, and cerebrovascular disease.
For their study the researchers analysed data from the UK Biobank study of 333,259 people who drank alcohol, and 21,710 never drinkers, recording those patients who had been hospitalized due to a cardiovascular event.
       Those participants who were included in the study were asked about their overall weekly alcohol intake and their intake of specific types of alcohol including beer, wine and spirits.
       The researchers found that for those participants who reported keeping within the current alcohol guidance, drinking less than 14 units a week, the risk of suffering a cardiovascular event was increased by 23% for each additional 1.5 pints of 4% strength beer.

        The authors pointed out that the acceptance of the J-shaped curve, which suggests that low to moderate alcohol consumption can be health beneficial, is wrong, and is the result of biases in existing epidemiological data.


Statin Intolerance ‘Overestimated and Overdiagnosed’


Statin intolerance is far less common than previously reported, according to a new meta-analysis, with data on more than 4 million adults from around the world, looking at reported statin adverse effects.

        The study puts the prevalence of statin intolerance at 6% to 10%, meaning that statin intolerance is “overestimated and overdiagnosed” in most cases.
It also means that “around 93% of patients on statin therapy can be treated effectively, with very good tolerability and without any safety issues. The reported prevalence of statin intolerance varies widely, from 2% to 3% to as high as 50%, chiefly because there is still a lack of a clear and easy way to apply the definition of statin intolerance.

         The study, conducted on behalf of the Lipid and Blood Pressure Meta-Analysis Collaboration and the International Lipid Expert Panel, and was published recently online in the European Heart Journal.


What Is the Healthiest Salt for You?

When we refer to “regular table salt,” it is most commonly in the form of sodium chloride, which is also a major constituent of packaged and ultraprocessed foods.
The best approach to finding the “healthiest salt” which really means the lowest in sodium is to look for the amount on the label. “Sodium-free” usually indicates less than 5 mg of sodium per serving, and “low-sodium” usually means 140 mg or less per serving. In contrast, regular table salt can contain as much as 560 mg of sodium in one serving.

       Other en vogue salts, such as pink Himalayan salt, sea salt, and kosher salt, are high in sodium content like regular table salt, but because of their larger crystal size, less sodium is delivered per serving. Most salt substitutes are reduced in sodium, with the addition of potassium chloride instead.

       The key to which salt is healthiest depends on the person. Our bodies need some sodium to function, just not in large amounts.


FDA Issues Guidance on Reducing Salt

Currently, the US sodium dietary guidelines for persons older than 14 stipulate 2300 mg/d, which is equivalent to 1 teaspoon a day. However it is estimated that the average person in the United States consumes more than this —around 3400 mg of sodium daily.

   In October 2021, the US Food and Drug Administration (FDA) published guidance on voluntary sodium limitations in commercially processed, packaged, and prepared food. The FDA’s short-term approach is to slowly reduce exposure to sodium in processed and restaurant food by 2025, on the basis that people will eventually get used to less salt, as has happened in the United Kingdom and other countries.

    Such strategies to reduce salt intake are now being used in national programs in several countries. Many of these successful initiatives include active engagement with the food industry to reduce the amount of sodium added to processed food, as well as public awareness campaigns to alert consumers to the dangers of eating too much salt. This includes increasing potassium in manufactured foods, primarily to target hypertension and heart disease.

Journal of Clinical Hypertension, Feb 2022


Striking’ Differences in BP When Wrong Cuff Size Is Used

Strong new evidence on the need to use an appropriately sized cuff in blood pressure (BP) measurement has come from the cross-sectional randomized trial Cuff (SZ).

     The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.

      However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference. The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, 7.4 mm Hg, respectively).

    Authors found that using the regular adult cuff in all individuals had striking differences in blood pressure.

EPI/Lifestyle 2022. Abstract. Presented March 2022


Get More Sleep, Lose More Weight: A Randomized Trial

I was fascinated reading this paper, which brings into the real world data that previously only existed in highly controlled laboratory experiments. When people sleep less, they eat more.

          Prior research in the field has been very consistent. If you take an individual and put them in a sleep lab and force them to sleep only 4 or 5 hours a night, they will eat more calories the next day. The mechanism of this relationship, the hormones, cytokines, and other substances that drive the sleep-hunger axis is still being worked out, but the relationship is clear.

          To figure it all out, researchers randomized 80 individuals, all of whom were overweight and getting less than 6.5 hours of sleep a night, to receive personalized sleep recommendations (sleep extension) to boost the time spent snoozing, or nothing. The recommendations were pretty straight forward — stuff we could all do a bit better: decreasing ambient light, creating a bedtime routine, limiting phone and TV use in bed, decreasing caffeine intake, and increasing exercise. Importantly, each participant was given a goal bedtime and wake-time schedule as an adherence goal.

           And the recommendations worked. After a 2-week run-in period, the intervention group got about 1.5 extra hours a night as documented by wrist monitors and stayed that way for the rest of the 2 weeks in the study.

          That’s not the interesting part, though. The researchers then dug into the energy balance in these individuals the calories they were taking in and those they were putting out using doubly labeled water to get accurate measurements. They found that the group randomized to sleep longer had a significant decrease in total energy intake (that’s calories in) during the study period, to the tune of around 150 fewer calories per day. They had no difference in total energy expenditure (calories out). And, since calories in went down and calories out stayed the same, the intervention group lost weight about a pound over 2 weeks.

In this review article, authors explore the famous pressure-natriuresis mechanism of salt and
water balance. This mechanism is the basis to understand how high dietary salt could increase
incidence of hypertension.
The article is published in the Electrolyte Blood Pressure journal and is available for free
through the following link

Electrolyte Blood Press. 2021 Dec;19(2):38-45.
doi: 10.5049/EBP.2021.19.2.38. Epub 2021 Dec 23.

Current Understanding of Pressure Natriuresis

Eun Ji Baek 1 , Sejoong Kim1 2
•1Department of Internal Medicine, Seoul National University Bundang Hospital,
Seongnam, Republic of Korea.
•2Department of Internal Medicine, Seoul National University College of Medicine,
Seoul, Republic of Korea.
• PMID: 35003284



Pressure natriuresis refers to the concept that increased renal perfusion pressure leads to a decrease in tubular reabsorption of sodium and an increased sodium excretion. The set point of blood pressure is the point at which pressure natriuresis and extracellular fluid volume are in equilibrium. The term “abnormal pressure
natriuresis” usually refers to the expected abnormal effect of a certain level of blood pressure on sodium excretion. Factors that cause abnormal pressure natriuresis are known. Sympathetic nerve system, genetic factors, and dietary factors may affect an increase in renal perfusion pressure. An increase in renal perfusion pressure increases renal interstitial hydrostatic pressure (RIHP). Increased RIHP affects tubular reabsorption through alterations in tight junctional permeability to sodium in proximal tubules, redistribution of apical sodium transporters, and/or release of renal autacoids. Renal autocoids such as nitric oxide, prostaglandin E2, kinins, and angiotensin II may also regulate pressure natriuresis by acting directly on renal tubule sodium transport. In addition, inflammation and reactive oxygen species may mediate pressure natriuresis. Recently, the use of new drugs associated with pressure natriuretic mechanisms, such as angiotensin receptor neprilysin inhibitor and sodium glucose co-transporter 2 inhibitors, has been consistently demonstrated to reduce mortality and hypertension-related complications. Therefore, the understanding of pressure natriuresis is gaining attention as an antihypertensive strategy. In this review, we provide a basic overview of pressure natriuresis to the target audience of nephrologists. 

Keywords: Blood pressure; Hypertension; Kidney; Pressure natriuresis; Sodium excretion.

Analysis Supports CAC for Personalizing Statin Use

In patients with intermediate risk of atherosclerotic cardiovascular disease along with risk-enhancing factors, coronary artery calcium scoring may help more precisely calculate their need for statin therapy.

Furthermore, when the need for statin treatment isn’t so clear and patients need additional risk assessment, the scoring can provide further information to personalize clinical decision making, according to a cross-sectional study of 1,688 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) published in JAMA Cardiology. In additon to coronary artery calcium (CAC), a low ankle brachial index (ABI) score is a marker for statin therapy, the study found.

The study looked at CAC scoring in the context of ABI and other risk-enhancing factors identified in the 2018 American Heart Association/American College of Cardiology cholesterol management guidelines: a family history of premature atherosclerotic cardiovascular disease (ASCVD), lipid and inflammatory biomarkers, chronic kidney disease, chronic inflammatory conditions, premature menopause or preeclampsia, and South Asian ancestry.

Any number of these factors can indicate the need for statins in people with borderline or intermediate risk. The guidelines also call for selective use of CAC to aid the decision-making process for statin therapy when the risk for developing atherosclerosis isn’t so clear.


ARBs Equal ACE Inhibitors for Hypertension, but Better Tolerated

In the largest comparison of angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.However, side e ffects were notably lower with ARBs.

This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected. “Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors add in the study, published in the journal Hypertension. They note that both drug classes have been on the market a long time, with proven efficacy in hypertension and a wide availability of inexpensive generic forms.

They also stress that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.


Statins Again Linked to Lower COVID-19 Mortality

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study. Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic. This is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type, However, it still an observational study and therefore falls short of a randomized study.

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease. While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect.


Myocarditis Tied to COVID-19 Shots More Common Than Reported?

 While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMR).

They also appear to represent two “distinct syndromes”. Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after either the first or second dose. Authors report their analysis in a research letter published in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence healthcare system and use the same EMR. The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); only 3% received the Johnson & Johnson vaccine. The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS), suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.


Aerobic Exercise Reduces BP in Resistant Hypertension

Aerobic exercise may help reduce blood pressure in patients whose hypertension responds poorly to medications, a new study suggests.

A randomized controlled clinical trial showed that patients with resistant hypertension assigned to a moderate-intensity aerobic exercise training program had lower blood pressure (BP) compared with patients who received usual care.

Resistant hypertension persists as a big clinical challenge because the available treatment options to lower blood pressure in this clinical population, namely drugs and renal denervation, show limited success. Aerobic exercise was safe and associated with a significant and clinically relevant reduction in 24-hour, daytime ambulatory, and office blood pressure. The findings were published in JAMA Cardiology. The researchers enrolled 53 patients aged 40 to 75 years with a diagnosis of resistant hypertension in this prospective, single-blinded trial.

Resistant hypertension was defined as having a mean systolic BP of 130 mm Hg or greater on 24-hour ambulatory BP monitoring and/or 135 mm Hg or greater during daytime hours while taking maximally tolerated doses of at least 3 antihypertensive agents, including a diuretic, or to have a controlled BP while taking 4 or more antihypertensive agents.

From March 2017 to December 2019 at two sites in Portugal, 26 patients were randomly assigned to a 12-week aerobic exercise training program involving three 40-minute supervised sessions per week in addition to usual care. Another 27 patients in the control group were allocated to receive usual care only.

24-hour ambulatory systolic blood pressure was reduced by 7.1 mm Hg (95% CI, −12.8 to −1.4; P = .02) in patients in the exercise group compared with the control group. In the exercise group, there were additional reductions of:

  • –5.1 mm Hg of 24-hour ambulatory diastolic blood pressure (95% CI, −7.9 to −2.3; P = .001)
  • –8.4 mm Hg of daytime systolic blood pressure (95% CI, −14.3 to –2.5, P = .006)
  • –5.7 mm Hg of daytime diastolic blood pressure (95% CI, −9.0 to −2.4; P = .001)
  • –10.0 mm Hg of office systolic blood pressure (95% CI, −17.6 to −2.5; P = .01)

Additionally, a significant improvement in cardiorespiratory fitness (5.05 mL/kg per minute of oxygen consumption; 95% CI, 3.5 – 6.6; P < .001) was observed in the exercise group compared with the control group.

Women Still Under-represented in CVD Trials, Despite Requirements

Women, and especially minority women, remain under-represented in most clinical cardiology trials, despite guidelines and legal requirements put forward years ago to ensure broader inclusivity, according to a new report released by the American College of Cardiology (ACC) Cardiovascular Disease in Women Committee.

Women are particularly under-represented in trials of coronary artery disease, heart failure with reduced ejection fraction, and arrhythmia studies involving devices and procedures, the committee found.

Gender-specific data are essential to optimal cardiovascular care and increasing awareness about trials is critical for everyone. Also, having trial information be available to all patients, regardless of where they live, who they are, or where they get care is important. The report was published in the Journal of the American College of Cardiology.

Barriers and Solutions

In the report, the committee outlines barriers to enrolling women in CV clinical trials and offers strategies to help increase participation of women in these trials. One key barrier is low referral rates to cardiologists and specialty programs for more aggressive care, leading to fewer women being treated by specialists who might be recruiting for clinical trials. The committee recommends expanding awareness of ongoing trials to primary care providers and to community and safety-net hospitals, and to offer more locations of trial enrollment if possible.

Another barrier is “ageism,” with older patients disproportionately under-represented in clinical trials overall, further compounding the under-representation of women in CV trials, as heart disease is significantly higher in older-age women. The committee recommends expanding age criteria and limiting exclusion criteria that disproportionately affects the elderly. “It is critical that age and comorbidities be expanded in clinical trial inclusion criteria to reflect real-world patient population.

A lack of awareness, trust, and logistical barriers is another obstacle to getting more women enrolled in CV clinical trials. Research has shown that women are more reluctant than men to consider trial participation.


A recently published review article by Perez et al, had discussed the association between hypertension, obesity, and the current COVID-19 pandemic. The article was published in the Current Hypertension Reports in June 2021 and the full article is free to read and to download at the journal website.

Hypertension, Obesity, and COVID-19: a Collision of Pandemics

Annalisa Perez 1, Mihran Naljayan 2, Imran Shuja 2, Andre Florea 2, Efrain Reisin 2


To highlight the epidemiology and pathophysiology of hypertension and obesity in COVID-19 infection RECENT FINDINGS: Hypertension and obesity have emerged as significant risk factors for contracting the COVID-19 virus and the subsequent severity of illness. ACE2 receptor expression and dysregulation of the RAAS pathway play important roles in the pathophysiology of these associations, as do the pro-inflammatory state and cytokine dysregulation seen in obesity. Some of these patterns have also been seen historically in other viral illnesses. Understanding the mechanisms behind the associations between COVID-19, hypertension, and obesity is important in developing effective targeted therapies and monitoring vaccine response and efficacy. More research is needed to apply our growing knowledge of the pathophysiology of COVID-19, hypertension, and obesity to prevention and treatment. Interventions focusing on lifestyle modification in managing hypertension and obesity can potentially have a positive impact on containing this pandemic and future viral illness outbreaks.


: ACE2 receptor; COVID-19; Hypertension; Obesity; RAAS.



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