Kefir peptide (Kef-1) as an emerging approach for the treatment of oxidative stress and inflammation in 2K1C mice

The benefits of Kefir consumption are due, in part, to the rich composition of bioactive molecules released from fermentation. Angiotensin-converting enzyme (ACE) inhibitors are bioactive molecules with potential use in...

Cardiotoxicity with antihypertensive drugs (literature review). Part II. Angiotensin converting enzyme inhibitors and multi-drug intoxication

Overdose with angiotensin converting enzyme (ACE) inhibitors, especially in combination with other cardiovascular drugs, is limited by a small number of publications. A serious problem is an overdose with combined drugs with a fixed dose and poisoning with several drugs at the same time. ACE inhibitors poisoning has serious complications and can lead to a fatal outcome. Acute ACE inhibitors poisoning comes out in disorders of hemocirculation, where one of the predisposing mechanisms of decompensation of blood circulation is the failure of cardiomyocytes, the pathogenesis of which is not fully studied. Therefore, the currently used the methods of cardio- and hemodynamic disorders correction which are currently used do not always give a positive effect. The review highlights the difficulties of clinical and functional diagnosis and treatment of overdose with ACE inhibitors, combined drugs with a fixed dose, as well as poisoning with several drugs.

Improved renal cancer prognosis among users of drugs targeting renin-angiotensin system

Purpose We explored renal cell cancer (RCC) survival among users of antihypertensive medication as hypertension is proposed to be a risk factor for RCC and ACE-inhibitors and angiotensin receptor blockers (ARBs) have been associated with improved prognosis of RCC. Methods Finnish cohort of 13,873 participants with RCC diagnosed between 1995–2012 was formed from three national databases. RCC cases were identified from Finnish Cancer Registry, medication usage from national prescription database and co-morbidities from Care Registry of Healthcare. Logistic regression was used to calculate odds ratios for metastatic tumor extent at the time of diagnosis. Risk of RCC specific death after diagnosis was analyzed using Cox regression adjusted for tumor clinical characteristics. Results A total of 5,179 participants died of RCC during the follow-up. No risk association was found for metastatic tumor extent for any drug group. ACE-inhibitors, but no other drug group were associated with decreased risk of RCC specific death overall (HR 0.88, 95% CI 0.82–0.95) compared to non-users. In time-dependent analysis high-dose use of ACE-inhibitors (392 Defined Daily Dose (DDD)/year), HR 0.54, 95% CI 0.45–0.66) and ARBs (786.1 DDD/year, HR 0.66, 95% CI 0.50–0.87) associated with improved RCC survival. No information of TNM-classification or tobacco smoking was available. Conclusion ACE-inhibitors and ARBs in high dose associated with improved RCC specific survival. This may reflect overall benefit of treating hypertension with medication targeting renin-angiotensin system (RAS) system among RCC patients. Further studies are needed to explore the role of RAS in RCC.

Long-Term Impact of Different Triple Combination Antihypertensive Medications on Blood Pressure Control, Metabolic Pattern and Incident Events: Data from the Brisighella Heart Study

The aim of this study was to comparatively evaluate clinical, laboratory and hemodynamic effects on the long term of different triple combination antihypertensive medications in a well-characterized Italian cohort. We considered the data of a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. For the current analysis, we excluded normotensive subjects, patients treated with <3 or ≥3 antihypertensive drugs without taking angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCB) and/or thiazide/thiazide-like diuretics. The remaining participants were divided into three groups depending on whether they were treated with Perindopril/Amlodipine/Indapamide, ACE-inhibitors (other than perindopril)/CCBs/Thiazide or ARBs/CCBs/Thiazide, either with separate drugs or fixed pill combinations. A further group of age- and sex-matched volunteers was selected as control and included patients receiving other antihypertensive treatments. The long-term (12 years) effects of the different antihypertensive treatments were compared among the pre-defined groups. During the observation period, there was a trend towards increase in both systolic and diastolic blood pressure (BP) in all the investigated subgroups (p for trend <0.05), but in the subgroup of patients treated with Perindopril/Amlodipine/Indapamide, such increase was significantly lower than in the other groups (p < 0.05). The combination treatment with renin-angiotensin system (RAS) modulators, CCBs and thiazide/thiazide-like diuretics was associated with significantly lower diastolic BP (p < 0.05) and more strictly controlled lipid pattern than other triple combination of anti-hypertensive medications. Patients treated with Perindopril/Amlodipine/Indapamide did not experience any age-related increase in serum levels of total cholesterol. Moreover, during the follow up none of them developed type 2 diabetes, nor had a need for a greater number of antihypertensive drugs to improve BP control, mainly because of a more stable BP control. Based on our observations, combination treatment with RAS modulators, amlodipine and thiazides/thiazide-like diuretics is more effective than other triple antihypertensive medications for lowering the diastolic BP and has a better impact on serum lipids. Perindopril/Amlodipine/Indapamide is associated with more protective metabolic profile than any other considered combination antihypertensive medications.

Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

A 2018 report from the American Heart Association shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin–angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, and heart failure, among others. It has been suggested that ACE inhibitors can alleviate the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that genetic variants of the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases, while other variants are associated with reduced risk of AD. In mice, ACE overexpression in the brain reduces symptoms of the AD model systems. Thus, we find two opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin–angiotensin system; (2) amyloid-degrading enzyme that hydrolyzes beta-amyloid, reducing amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to AD to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during midlife, leading to age-related later events.

Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study

ObjectivesSARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use.DesignThis is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality.SettingMedical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality.Participants9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed.Outcome measureDeath from any cause within 60 days of COVID-19 diagnosis was examined.ResultsDiscontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2–1.7). Initiating (OR: 0.3; 95% CI 0.2–0.5) or continuous (OR: 0.6; 95% CI 0.5–0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment.ConclusionsRecent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.