Effects Of Antihypertensive Medications Research Articles

Abstract P134: Effects of Antihypertensive Medications on All-cause Dementia: Evidence from Target Trial Emulation of 3 Million US Veterans

Introduction: Hypertension is a modifiable risk factor for all-cause dementia. Mechanistic and observational evidence suggest angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) may differentially affect dementia risk. Objective and Methods: We used longitudinal electronic health records of over 3 million US Veterans to conduct a target trial emulation with a new-user, active comparator design. We compared the intention-to-treat effect of initiating ARBs vs ACEIs (1/1/2000-12/31/2022) on dementia risk. We controlled for >60 baseline covariates using inverse probability (IP) of treatment and overlap weighting. Dementia was ascertained using diagnosis codes and medications. We nonparametrically estimated the cause-specific cumulative incidence for each treatment group under the competing risk of death then computed treatment effects as weighted risk ratios with bootstrapped 95% confidence intervals. We also evaluated all-cause death and a composite outcome of dementia or death (dementia/Death) using Cox regression. Results: Among the 3,190,356 included Veterans (mean age 63, 5% female, 64% White, and 15% Black), 13% initiated ARBs and 87% initiated ACEIs. Overall, 8% developed dementia and 35% died over a median follow-up of 8 years. The risk of dementia was lower among ARB vs ACEI initiators (10-year risk ratio: 0.95 (0.94, 0.96)). The risk of all-cause death and dementia/Death were also lower among ARB vs ACEI initiators with overlap weighting. Conclusions: Among US Veterans with hypertension, ARB vs ACEI initiation was associated with a moderately lower risk of dementia. Future work assessing sustained treatment with ARB vs ACEI is needed to inform their use to reduce dementia risk.

O81 EFFECT OF ANTIHYPERTENSIVE MEDICATIONS ON URINARY SODIUM TO POTASSIUM (Na/K) RATIO

Background: The urinary sodium to potassium ratio (Na/K) greater than 2 indicating either excess sodium or insufficient potassium intake. However, the effect of antihypertensive medications on the urinary Na/K ratio has not been evaluated. We hypothesized that antihypertensive medication would acutely affect the urinary Na/K ratio. Methods: Male and female C57BL/6J mice, 14 weeks old, and a separate cohort of 24-month-old mice were subjected to a regular chow diet (NaCl 0.4%) and a high salt diet (4%). Urinary Na/K ratios in spot urine samples were measured three times a week. After baseline measurements, all animals were treated with one antihypertensive medication for 2 weeks, followed by a one-week washout period. The effects of enalapril (25 mg/kg/day), hydrochlorothiazide (25 mg/kg/day), and amlodipine (10 mg/kg/day)—were compared under a high salt diet mimicking human salt consumption. Urinary Na/K ratios collected on day 1 (acute) and day 8 (subacute) after initiating medication were compared to the vehicle period using a two-way ANOVA. Medication was administered with food using gel food pellets. Results: Under regular chow, the urinary Na/K ratio was 0.65±0.58 (n=15) with no interaction between sex or age (all p>0.05). Under a high salt diet, the urinary Na/K ratio increased to 4.5±2.2 (p<0.01 vs. regular chow) with no differences between sex and age. After the washout period, enalapril, both acutely and subacutely, did not affect the Na/K ratio. Similarly, hydrochlorothiazide did not affect the Na/K ratio in either period. However, amlodipine reduced the Na/K ratio in both acute and subacute periods (p<0.001). No interaction was observed with sex or age. The effect of amlodipine was related to higher potassium excretion (43.9±23 vs. 81.6±33 meq/L; p<0.001) with no changes in sodium excretion (152.2±75 vs. 173.3±43.5 meq/L; p=0.8). Conclusion: The Na/K ratio reflects salt and potassium consumption. The Na/K ratio is not affected by enalapril or hydrochlorothiazide. Amlodipine decreases the Na/K ratio acutely and subacutely due to increased potassium excretion.

Dosing time optimization of antihypertensive medications by including the circadian rhythm in pharmacokinetic-pharmacodynamic models.

Blood pressure (BP) follows a circadian variation, increasing during active hours, showing a small postprandial valley and a deeper decrease during sleep. Nighttime reduction of 10-20% relative to daytime BP is defined as a dipper pattern, and a reduction of less than 10%, as a non-dipper pattern. Despite this BP variability, hypertension's diagnostic criteria and therapeutic objectives are usually based on BP average values. Indeed, studies have shown that chrono-pharmacological optimization significantly reduces long-term cardiovascular risk if a BP dipper pattern is maintained. Changes in the effect of antihypertensive medications can be explained by circadian variations in their pharmacokinetics (PK) and pharmacodynamics (PD). Nevertheless, BP circadian variation has been scarcely included in PK-PD models of antihypertensive medications to date. In this work, we developed PK-PD models that include circadian rhythm to find the optimal dosing time (Ta) of first-line antihypertensive medications for dipper and non-dipper patterns. The parameters of the PK-PD models were estimated using global optimization, and models were selected according to the lowest corrected Akaike information criterion value. Simultaneously, sensitivity and identifiability analysis were performed to determine the relevance of the parameters and establish those that can be estimated. Subsequently, Ta parameters were optimized to maximize the effect on BP average, BP peaks, and sleep-time dip. As a result, all selected models included at least one circadian PK component, and circadian parameters had the highest sensitivity. Furthermore, Ta with which BP>130/80 mmHg and a dip of 10-20% are achieved were proposed when possible. We show that the optimal Ta depends on the therapeutic objective, the medication, and the BP profile. Therefore, our results suggest making chrono-pharmacological recommendations in a personalized way.

Randomized controlled trials of biomarker targets.

Randomized controlled trials are used to estimate the causal effect of a treatment on a health outcome of interest in a patient population. Often the specified treatment in a randomized controlled trial is a medical intervention-such as a drug or procedure-experienced directly by the patient. Sometimes the "treatment" in a randomized controlled trial is a target-such as a goal biomarker measurement-that the patient's physician attempts to reach using available medications or procedures. Large randomized controlled trials of biomarker targets are common in clinical research, and trials have been conducted to compare targets in the management of hypertension, diabetes, anemia, and acute respiratory distress syndrome. However, different randomized controlled trials intended to evaluate the same biomarker targets have produced conflicting recommendations, and meta-analyses that aggregate results of trials of biomarker targets have been inconclusive. We use causal reasoning to explain why randomized controlled trials of biomarker targets can arrive at conflicting or misleading conclusions. We describe four key threats to the validity of trials of targets: (1) intention-to-treat analysis can be misleading when a direct effect of target assignment on the outcome exists due to lack of blinding; (2) incomparability in results across trials of targets; (3) time-varying adaptive treatment strategies; and (4) Goodhart's law, "when a measure becomes a target, it ceases to be a good measure." We illustrate these findings using evidence from 15 randomized controlled trials of blood pressure targets for management of hypertension. Randomized trials of blood pressure targets exhibit substantial variation in the trial patient populations and antihypertensives used to achieve the blood pressure targets assigned in the trials. The trials did not compare or account for time-varying treatment strategies used to reach the randomized targets. Possible "off-target" effects of antihypertensive medications needed to reach lower blood pressure targets may explain the absence of a clear benefit from intensive blood pressure control. Researchers should critically assess meta-analyses of trials of targets for variation in the types, distributions, and off-target effects of therapies studied. Trial investigators should release detailed information about the biomarker targets compared in new randomized trials, as well as confounders, treatments delivered, and outcomes. New randomized controlled trials should experimentally compare treatment algorithms incorporating biomarkers, rather than targets alone. Causal inference methodology that adjusts for time-varying confounding should be used to compare time-varying treatment strategies in observational settings.

Heart diseases, hypertension and effects of antihypertensive medications: Is hypertension a true risk factor of heart diseases?

Heart diseases (HD) are the leading cause of deaths in the world. Many studies have been done on the relationships among hypertension, HD and antihypertensive medications. Most of the studies find that hypertension is a significant risk factor of HD, but there are some studies in which hypertension is not a risk factor. As antihypertensive medications are routinely prescribed to prevent HD, it is necessary to evaluate the effects of these and other risk factors of HD. The relationship between hypertension and HD was analyzed using 6,773,464 medical checkups obtained from the JMDC Claims Database obtained from January 2005 to September 2019. Factors potentially affecting HD, including blood pressures (BP) and usage of antihypertensive medications, were evaluated using 2,861,769 observations. To avoid the causality problem, probit models were used to analyze the probability of an individual who had no history of HD at year t developing HD by year t + 1. A positive relation between systolic blood pressure (SBP) and HD was found in the equation without any other covariates. However, the significant relation between HD and BP disappeared when the models contained various other factors as covariates. When a 10-year age or longer interval was used in the model, a positive relation between the two variables was found, suggesting that SBP works as a proxy variable. Taking antihypertensive medications greatly increases the probability of developing HD in the next year. Higher levels of cholesterols decrease the probability of developing HD. Unlike many previous studies, no significant relationship between HD and hypertension was found in the models containing multiple covariates. The accepted relation might actually be spurious, and it is important to select covariates carefully. Taking antihypertensive medications appears to increase the probability of developing HD in the next year, suggesting the need for further research and greater caution in the use of antihypertensive medications.

Effect of Anti-Hypertensive Medication on Plasma Concentrations of Lysyl Oxidase: Evidence for Aldosterone-IL-6-Dependent Regulation of Lysyl Oxidase Blood Concentration.

Lysyl oxidase (LOX) is a secretory protein that catalyzes elastin and collagen cross-linking. Lowering LOX expression and activity in endothelial cells is associated with a high risk of aneurysms and vascular malformation. Interleukin-6 (IL-6), elevated in hypertension, is known to suppress LOX expression. The influence of anti-hypertensive medication on the plasma LOX concentration is currently unknown. In a cohort of 34 patients diagnosed with resistant hypertension and treated with up to nine different drugs, blood concentration of LOX was analyzed to identify drugs that have an impact on plasma LOX concentration. Key findings were confirmed in a second independent patient cohort of 37 patients diagnosed with dilated cardiomyopathy. Blood concentrations of aldosterone and IL-6 were analyzed. In vitro, the effect of IL-6 on LOX expression was analyzed in endothelial cells. Patients receiving aldosterone antagonists had the highest plasma LOX concentration in both cohorts. This effect was independent of sex, age, blood pressure, body mass index, and co-medication. Blood aldosterone concentration correlates with plasma IL-6 concentration. In vitro, IL-6 decreased the expression of LOX in endothelial cells but not fibroblasts. Aldosterone was identified as a factor that affects blood concentration of LOX in an IL-6-dependent manner.

The effects of antihypertensive medications on severity and outcomes of COVID19.

The effects of antihypertensive medications on severity and outcomes of COVID19.

Effect of antihypertensive medications on sleep status in hypertensive patients.

Antihypertensive medication is an effective way to control blood pressure. However, some studies reported that it may affect patients' sleep quality during the treatment. Due to the inconsistency of present results, a comprehensive systematic review and network meta-analysis are needed. Electronic databases (MEDLINE, EMBASE, WEB OF SCIENCE, PUBMED) were searched up to April 10th, 2021 including no restriction of publication status. Randomized controlled trials (RCTs) or quasi-experimental studies or cohort studies were eligible. The network meta-analysis was used within a Bayesian framework. Finally, 16 publications (including 12 RCTs and 4 quasi-experimental studies) with 404 subjects were included in this study. Compared to placebo, the results of the network meta-analysis showed that diuretics were effective in improving sleep apnea with a mean difference (MD) of - 15.47 (95% confidence interval [CI]: - 23.56, - 6.59) which was consistent with the direct comparison result (MD: - 17.91; 95% CI - 21.60, - 14.23). In addition, diuretics were effective in increasing nocturnal oxygen saturation with an MD of 3.64 (95% CI 0.07, 7.46). However, the effects of β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and the others on sleep apnea were not statistically significant. Additionally, the effects of antihypertensive medication on the total sleep time (min), rapid eye movement (%), and sleep efficiency (%) were not statistically significant. Our study found that diuretics could effectively reduce the severity of sleep apnea in hypertensive patients. However, the effects of antihypertensive drugs on sleep characteristics were not found. The online version contains supplementary material available at 10.1007/s41105-022-00391-8.

Antihypertensive medication and outcome in patients with COVID-19 compared to non-COVID respiratory infections

BackgroundRecent reports suggested no adverse effects of antihypertensive medication including inhibitors of the renin-angiotensin system on outcome of patients with coronavirus disease 19 (COVID-19). However, most of these studies lack adequate control groups, and regional and socio-economic differences may additionally affect clinical course and outcome of COVID-19.MethodsIn the prospective observational cohort COrona VIrus surviVAl (COVIVA) study at our university hospital, we consecutively enrolled patients presenting to the emergency department with symptoms suggestive of COVID-19 between March and June 2020. Patients tested positive for COVID-19 (cases) were compared with patients tested negative, who had a respiratory infection (respiratory control). Primary outcome measure was the composite of ICU admission, 3'-day mortality or rehospitalization for respiratory symptoms.ResultsThe final analysis consisted of 191 patients with COVID-19 and 323 respiratory controls. Sixty cases (31.4%) and 87 (26.9%) respiratory control patients were on ACE inhibitors (ACE-I) or angiotensin II receptor blockers (ARB). In unadjusted models the hazard ratio [95% CI] for the composite outcome for patients on ACE-I/ARBs was 2.36 [1.34; 4.16], p=0.003 and 2.05 [1.03; 4.09], p=0.04 among patients with COVID-19 and respiratory controls, respectively. The corresponding multivariable adjusted HRs were 1.32 [0.68; 2.55], p=0.41 and 1.20 [0.58; 2.48], p=0.62. Furthermore, we did not observe an increased risk for the outcome when assessing ACE-Is and ARBs separately or other antihypertensive agents, both in COVID-19 patients and respiratory controls (Table).ConclusionsIn a Swiss cohort of patients with COVID-19 or non-COVID respiratory controls treatment with ACE-I/ARBs or other antihypertensive medication was not associated with adverse events after accounting for comorbidities and risk factors.Funding AcknowledgementType of funding sources: Foundation. Main funding source(s): Foundation for Cardiovascular Research Basel (FCVR Basel)Swiss Heart Foundation

The Effect of Antihypertensive Medications on Testing for Primary Aldosteronism.

Primary aldosteronism (PA) is a potentially curable form of secondary hypertension caused by excessive renin-independent aldosterone secretion, leading to increased target organ damage and cardiovascular morbidity and mortality. The diagnosis of PA requires measuring renin and aldosterone to calculate the aldosterone-to-renin ratio, followed by confirmatory tests to demonstrate renin-independent aldosterone secretion and/or PA subtype differentiation. Various antihypertensive drug classes interfere with the renin-angiotensin-aldosterone axis and hence evaluation for PA should ideally be performed off-drugs. This is, however, often precluded by the risks related to suboptimal control of blood pressure and serum potassium level in the evaluation period. In the present review, we summarized the evidence regarding the effect of various antihypertensive drug classes on biochemical testing for PA, and critically appraised the issue whether and which antihypertensive medications should be withdrawn or, conversely, might be continued in patients evaluated for PA. The least interfering drugs are calcium antagonists, alpha-blockers, hydralazine, and possibly moxonidine. If necessary, the testing may also be attempted during treatment with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers but renin and aldosterone measurements must be interpreted in the context of known effects of these drugs on these parameters. Views are evolving on the feasibility of testing during treatment with mineralocorticoid receptor antagonists, as these drugs are now increasingly considered acceptable in specific patient subsets, particularly in those with severe hypokalemia and/or poor blood pressure control on alternative treatment.

Association Between Genetic Variation in Blood Pressure and Increased Lifetime Risk of Peripheral Artery Disease.

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Effects of antihypertensive medication and high‐intensity interval training in hypertensive metabolic syndrome individuals

Pharmacological and non-pharmacological therapies are simultaneously prescribed when treating hypertensive individuals with elevated cardiovascular risk (ie, metabolic syndrome individuals). However, it is unknown if the interactions between antihypertensive medication (AHM) and lifestyle interventions (ie, exercise training) may result in a better ambulatory blood pressure (ABP) control. To test this hypothesis, 36 hypertensive individuals with metabolic syndrome (MetS) under long-term prescription with AHM targeting the renin-angiotensin-aldosterone system (RAAS) were recruited. Before and after 4months of high-intensity interval training (HIIT), participants completed two trials in a double-blind, randomized order: (a) placebo trial consisting of AHM withdrawal for 3days and (b) AHM trial where individuals held their habitual dose of AHM. In each trial, 24-h mean arterial pressure (MAP) was monitored and considered the primary study outcome. Secondary outcomes included plasma renin activity (PRA) and aldosterone concentration to confirm withdrawal effects on RAAS, along with the analysis of urine albumin-to-creatinine ratio (UACR) to assess kidney function. The results showed main effects from AHM and HIIT reducing 24-h MAP (-5.7mmHg, p<0.001 and -2.3mmHg, p=0.007, respectively). However, there was not interaction between AHM and HIIT on 24-h MAP (p=0.240). There was a main effect of AHM increasing PRA (p<0.001) but no effect on plasma aldosterone concentration (p= 0.368). HIIT did not significantly improve RAAS hormones or the UACR. In conclusion, AHM and HIIT have independent and additive effects in lowering ABP. These findings support the combination of habitual AHM with exercise training with the goal to reduce ABP in hypertensive MetS individuals.

Study protocol for the randomized controlled EVA (early vascular adjustments) trial: tailored treatment of mild hypertension in pregnancy to prevent severe hypertension and preeclampsia

BackgroundIn contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth.MethodsWomen diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes.DiscussionThis trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression.Trial registrationNCT02531490, registered on 24 August 2015.

Is there any role of renin-angiotensin system inhibitors in modulating inflammatory bowel disease outcome?

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been associated with improved outcomes in inflammatory bowel disease. We aimed to investigate any possible effect of antihypertensive medications on inflammatory bowel disease course. One hundred and fifty inflammatory bowel disease patients with hypertension were compared using a 1:1 ratio with age- and gender-matched control patients with inflammatory bowel disease. The class of antihypertensive medication, traditional risk factors for atherosclerosis, inflammatory bowel disease characteristics, and history (surgery, hospitalizations, and treatment) were retrospectively analyzed. Of 150 (44.7% Crohn's disease) patients with hypertension, 46.7% were on angiotensin receptor blockers, 30.6% on angiotensin-converting enzyme inhibitors, 40% on β-blockers, and 40.7% on calcium channel blockers. Univariate analysis revealed significantly higher rates of traditional risk factors for atherosclerosis among antihypertensive users. When analyzing by class of antihypertensive medication, angiotensin receptor blockers were significantly associated with milder course as indicated by less frequent immunomodulator (P = 0.039) and steroid use (P = 0.041). Rates of lifetime steroids were statistically significantly lower among angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (odds ratio = 1.191, 95% confidence interval, 1.005-1.411). After adjustment with confounding factors, only angiotensin receptor blockers were associated with milder inflammatory bowel disease course (P = 0.037) and lower rates of immunomodulator use (P = 0.038). Our study suggests a possible protective effect of angiotensin receptor blockers on overall inflammatory bowel disease course by targeting the renin-angiotensin system. Their effect on inflammatory bowel disease needs to be studied in larger cohorts.

Change in Blood Pressure Variability Among Treated Elderly Hypertensive Patients and Its Association With Mortality.

BackgroundInformation is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long‐term mortality in an elderly hypertensive population.Methods and ResultsWe used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24‐hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow‐up). Weighted day‐night systolic BPV was calculated for both baseline and follow‐up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV, stable: high BPV, decline: high to low, and increase: low to high. We observed an annual decline (mean±SD: −0.37±1.95; 95% CI, −0.54 to −0.19; P<0.001) in weighted day‐night systolic BPV between baseline and follow‐up. Having constant stable: high BPV was associated with an increase in all‐cause mortality (hazard ratio: 3.03; 95% CI, 1.67–5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62–8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow‐up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group.ConclusionsOur results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow‐up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long‐term mortality.

1415Dose antihypertensive medication improve accelerated age-dependent decline of GFR in hypertension?

Abstract Background/Introduction An impairment of kidney function is a risk not only for end stage renal disease but also for cardiovascular events. Hypertension is known to accelerate an age-dependent decline in glomerular filtration rate (GFR). Purpose Effects of antihypertensive medications on yearly changes of estimate GFR (eGFR) in hypertensive patients were investigated. Methods Consecutive 5110 subjects (male=3196, 52.3±11.3 year-old) who participated in our physical check-up program during 2010 and 2012 were enrolled and followed up for 5 years. The average and the yearly change of eGFR during the 5 years were calculated in each individual and the both values were compared in hypertensive and normotensive subjects. Effect of antihypertensive medication on eGFR was also investigated. The modified Modification of Diet in Renal Disease study formula for the Japanese population was used for calculating eGFR. Results In hypertensive subjects (n=1408), the baseline and the average of eGFR were smaller (74.8±14.6 vs. 80.4±13.6, p&lt;0.001 and 72.1±13.2 vs. 77.9±11.9 mL/min per 1.73 m2, p&lt;0.001, respectively) and the yearly decline of eGFR was greater (0.96±1.41 vs. 0.84±1.19 mL/min per 1.73 m2 per year, p&lt;0.01) than in normotensive subjects (n=3702). The baseline and the average of eGFR were smaller in hypertensive patients with (n=1234) than without (n=174) antihypertensive medication (74.3±14.6 vs. 78.3±13.8, p&lt;0.001 and 71.7±13.2 vs. 74.9±12.7 mL/min per 1.73 m2, p&lt;0.01, respectively). Although the yearly decline of eGFR in hypertensive patients with medication tended to be smaller than the decline in those without medication (0.94±1.41 vs. 1.09±1.42 mL/min per 1.73 m2 per year), this did not reach a statistical significance (p=0.213). Neither the number, classes of antihypertensive medications nor systolic blood pressure during the follow-up period did affect the average or yearly decline of eGFR in hypertensive patients. Conclusions As compared to normotensive subjects, eGFR was reduced and a yearly decrease in eGFR during the 5 years was accelerated in hypertensive patients. Although antihypertensive medication may reduce an accelerated age-dependent decline of kidney function in hypertension, observational period in this study was too short to clarify such beneficial effects of antihypertensive medications.

Towards precision critical care management of blood pressure in hemorrhagic stroke patients using dynamic linear models.

Finding optimal blood pressure (BP) target and BP treatment after acute ischemic or hemorrhagic strokes is an area of controversy and a significant unmet need in the critical care of stroke victims. Numerous large prospective clinical trials have been done to address this question but have generated neutral or conflicting results. One major limitation that may have contributed to so many neutral or conflicting clinical trial results is the “one-size fit all” approach to BP targets, while the optimal BP target likely varies between individuals. We address this problem with the Acute Intervention Model of Blood Pressure (AIM-BP) framework: an individualized, human interpretable model of BP and its control in the acute care setting. The framework consists of two components: one, a model of BP homeostasis and the various effects that perturb it; and two, a parameter estimator that can learn clinically important model parameters on a patient by patient basis. By estimating the parameters of the AIM-BP model for a given patient, the effectiveness of antihypertensive medication can be quantified separately from the patient’s spontaneous BP trends. We hypothesize that the AIM-BP is a sufficient framework for estimating parameters of a homeostasis perturbation model of a stroke patient’s BP time course and the AIM-BP parameter estimator can do so as accurately and consistently as a state-of-the-art maximum likelihood estimation method. We demonstrate that this is the case in a proof of concept of the AIM-BP framework, using simulated clinical scenarios modeled on stroke patients from real world intensive care datasets.

Three Public Health Interventions Could Save 94 Million Lives in 25 Years.

Preventable noncommunicable diseases, mostly cardiovascular diseases, are responsible for 38 million deaths annually. A few well-documented interventions have the potential to prevent many of these deaths, but a large proportion of the population in need does not have access to these interventions. We quantified the global mortality impact of 3 high-impact and feasible interventions: scaling up treatment of high blood pressure to 70%, reducing sodium intake by 30%, and eliminating the intake of artificial trans fatty acids. We used global data on mean blood pressure levels and sodium and trans fat intake by country, age, and sex from a pooled analysis of population health surveys, and regional estimates of current coverage of antihypertensive medications, and cause-specific mortality rates in each country, as well, with projections from 2015 to 2040. We used the most recent meta-analyses of epidemiological studies to derive relative risk reductions for each intervention. We estimated the proportional effect of each intervention on reducing mortality from related causes by using a generalized version of the population-attributable fraction. The effect of antihypertensive medications and lowering sodium intake were modeled through their impact on blood pressure and as immediate increase/reduction to the proposed targets. The combined effect of the 3 interventions delayed 94.3 million (95% uncertainty interval, 85.7-102.7) deaths during 25 years. Increasing coverage of antihypertensive medications to 70% alone would delay 39.4 million deaths (35.9-43.0), whereas reducing sodium intake by 30% would delay another 40.0 million deaths (35.1-44.6) and eliminating trans fat would delay an additional 14.8 million (14.7-15.0). The estimated impact of trans fat elimination was largest in South Asia. Sub-Saharan Africa had the largest proportion of premature delayed deaths out of all delayed deaths. Three effective interventions can save almost 100 million lives globally within 25 years. National and international efforts to scale up these interventions should be a focus of cardiovascular disease prevention programs.

Effect of Antihypertensive Medications on Sepsis-Related Outcomes: A Population-Based Cohort Study.

Although the effect of antihypertensive agents on sepsis has been studied, evidence for survival benefit was limited in the literature. We investigated differences in sepsis-related outcomes depending on the antihypertensive drugs given prior to sepsis in patients with hypertension. Population-based cohort study. Sample cohort Database of the National Health Insurance Service from 2003 to 2013 in South Korea. Patients over 30 years old who were diagnosed with sepsis after receiving hypertension treatment. None. Primary outcomes, 30-day and 90-day mortality rates, were analyzed for differences among three representative antihypertensive medications: angiotensin- converting enzyme inhibitors or angiotensin II receptor blockers, calcium channel blockers, and thiazides. In total, 4,549 patients diagnosed with hypertension prior to hospitalization for sepsis were identified. The 30-day mortality was significantly higher among patients who did not receive any medications within 1 month before sepsis (36.8%) than among patients who did (32.0%; p < 0.001). The risk for 90-days mortality was significantly lower in prior angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker users (reference) than in other drug users (odds ratio, 1.27; 95% CI, 1.07-1.52). There was no difference in the risk for 30-day and 90-day mortality depending on whether calcium channel blockers or thiazides were used. Use of calcium channel blockers was associated with a decreased risk for inotropic agent administration, compared with those of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (odds ratio, 1.23; 95% CI, 1.05-1.44) and thiazides (odds ratio, 1.33; 95% CI, 1.12-1.58). In patients with sepsis, lower mortality rate was associated with prior use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers not with use of calcium channel blockers or thiazides. The requirement of inotropic agents was significantly lower in prior use of calcium channel blockers, although the survival benefits were not prominent.

Effect of Anti-Hypertensive Medications on Hemorrhagic Transformation in Ischemic Stroke (P3.3-047)

Effect of Anti-Hypertensive Medications on Hemorrhagic Transformation in Ischemic Stroke (P3.3-047)