Chronic Diseases and Translational Medicine最新文献

The American College of Cardiology/American Heart Association defines resistant hypertension (RH) as a clinical blood pressure (BP) reading of >130/80 mmHg in patients taking three antihypertensive drugs, including a renin–angiotensin system inhibitor, a calcium channel blocker (CCB), and a diuretic at well-tolerated doses.^{1, 2} It is reported from multiple population-based surveys that in the United States, there is an approximately 12%–15% prevalence of RH among adults diagnosed with hypertension.² A prospective study demonstrates that 20% of people diagnosed with RH had primary hyperaldosteronism.^{3, 4} In addition to the classic three antihypertensive drugs, spironolactone and mineralocorticoid are also administered for RH. However, with respect to the safety profile of spironolactone, it has been reported to have several side effects such as low testosterone production, menstrual irregularities, and excessively raised serum potassium levels, leaving the drug unfit for the longitudinal therapeutic purpose of treating RH.⁵

Clinical research has demonstrated that aldosterone synthesis inhibitors lower circulating aldosterone levels by directly blocking the synthesis of aldosterone rather than blocking its receptor activity, subsequently lowering BP.⁶ The first aldosterone synthase inhibitor to be developed was Osilodrostat (LCI699), which was intended to reduce serum aldosterone levels and manage hypertension. It was soon discovered, nevertheless, that Osilodrostat also inhibits 11-beta hydroxylase (CYP11B1), which lowers serum cortisol levels.⁷

Perhaps due to decreased cortisol levels, there were many reasons for the administration of Osilodrostat; thus, what was needed for the resistance was a selective aldosterone inhibitor, which was conceived and licensed by CinCor Pharma Inc. Baxdrostat, a drug in phase 2 clinical trials, exemplifies exceptional selective suppression of aldosterone synthase without blocking 11-beta hydroxylase.⁸

Animal model studies conducted on cynomolgus monkeys suggested that this drug inhibits the production of aldosterone without influencing the increase in cortisol caused by adrenocorticotropic hormone.⁹ Furthermore, research involving healthy volunteers validated these findings (ClinicalTrials.gov Identifier: NCT01995383).⁸ Multiple ascending doses of Baxdrostat were later investigated for safety, pharmacokinetics, and pharmacodynamics in a Phase I trial, which found that Baxdrostat was well tolerated, safe, and caused a dose-dependent decrease in plasma aldosterone but not cortisol.

Baxdrostat was tested in a Phase II trial^{8, 10} that was randomized, double-blind, placebo-controlled, and dose-ranging in adults with treatment-resistant hypertension (Brig

Patients with familial hypercholesterolemia (FH) have elevated low-density lipoprotein cholesterol (LDL-C) levels and are at high risk of premature cardiovascular disease.¹ Heterozygous FH (HeFH) is one of the commonest genetic disorders, and is more frequent among those with ischemic heart disease (IHD), atherosclerotic cardiovascular disease (ASCVD) and premature IHD.² FH screening, followed by effective lipid-lowering therapy (LLT) including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor can slow or even reverse plaque progression and reduce risk.³

Optical coherence tomography (OCT) is a promising intravascular approach in visualizing coronary plaque morphology, assessing disease progression, and monitoring response to treatments with high axial resolution (10–15 µm).⁴ Several related clinical trials have demonstrated that statins alone or in combination with PCSK9 inhibitors produce regression of atherosclerosis.^5-7

Here, we presented a patient with premature IHD, who was a probable HeFH and received evolocumab (Repatha®) after percutaneous coronary intervention (PCI). We followed his clinical and laboratory results for over 3.5 years, and used OCT to monitor vascular response to PCSK9 inhibitor treatment.

A 34-year-old man with hyperlipidemia and hypertension self-presented to the emergency department due to exertional chest pain for 3 days on November 23, 2019. His height, body weight, and body mass index were 170 cm, 95 kg, and 32.9 kg/m², respectively. Cardiac troponin I (cTnI) was mildly elevated at 0.297 ng/mL, and electrocardiogram demonstrated ST-T changes in I, aVL, II, III, aVF, V5–V9 leads, suggesting acute inferior, lateral, and posterior myocardial infarction. After medical stabilization, he underwent coronary angiography (CAG), revealing triple vessel disease (Figure 1) and received percutaneous transluminal coronary angioplasty to the left circumflex artery (LCX) with a stent on November 24, and another drug balloon dilation at posterior descending artery (PDA) on December 3. Standard postoperative treatment was given and the patient had no episodes of chest tightness accompanied by a regression of cTnI.

Laboratory examinations showed that his LDL-C and triglyceride (TG) levels were upper normal (Figure 2). Considering his LDL-C level remained at 3.45 mmol/L after combined oral LLT (statin + ezetimibe), we estimated his baseline LDL-C to be over 6.50 mmol/L. Besides, his father has a history of hyperlipidemia and PCI. According to the criteria of the Dutch Lipid Clinic Network (DLCN),⁸ the patient could be diagnosed as probable FH (his DLCN score = 8).

Based on early onset acute coronary syndromes (ACS) combined with multiple high-risk conditions, the patient could be defined as very high-risk ASCVD patient according to Americ

Estimated age-adjusted comparative diabetes prevalence in adults (20–79 years) in Pakistan from the year 2011 to 2021.

Hypertension, also known as high blood pressure (BP), affects millions of people worldwide. Beyond its well-documented cardiovascular consequences, hypertension has been uncovered an association with cognitive impairment.¹ This is a growing concern, as the number of people with hypertension is expected to increase in the coming years, particularly in developing countries.

Several studies have highlighted a robust association between hypertension and cognitive decline, including a risk of dementia, vascular cognitive impairment and Alzheimer's disease.^2-4 The mechanisms behind this relationship are complex and multifactorial, involving both vascular and nonvascular pathways.² Chronic hypertension leads to structural and functional changes in blood vessels, causing reduced cerebral blood flow, small vessel disease and the development of white matter lesions. These alterations contribute to cognitive impairment, affecting memory, attention and executive functions.³ Emerging evidence suggests that hypertension disrupts brain function through various mechanisms. One key process is the damage inflicted on blood vessels in the brain. The constant high pressure weakens arterial walls, leading to arteriosclerosis, reduced elasticity and the formation of blood clots. These vascular changes directly impact the brain, increasing the risk of ischemic events and reducing the brain's ability to receive adequate oxygen and nutrients.⁴ Moreover, hypertension promotes the accumulation of beta-amyloid plaques and tau tangles, hallmark signs of Alzheimer's disease. It also triggers inflammation, oxidative stress and neurotoxicity, accelerating the progression of cognitive decline. Hypertension-related cognitive impairment often manifests as deficits in attention, processing speed and executive functions. The decline can range from mild cognitive impairment (MCI) to more severe forms, adversely affecting the patient's quality of life.^2-4

Two recent cross-sectional studies shed light on the link between hypertension and cognitive impairment in different populations.^{5, 6} In Tanzania, a study conducted at a tertiary cardiovascular hospital examined the prevalence and correlates of cognitive impairment among hypertensive patients. The results showed that 43.6% of hypertensive participants experienced cognitive impairment.⁵ Another cross-sectional study in China explored the associations between hypertension characteristics and cognitive functions in individuals over the age of 45.⁶ The study revealed an age-dependent correlation, with untreated and treated but uncontrolled hypertension, as well as elevated pulse pressure, showing adverse effects on cognition, particularly in people aged 60 and above.⁶

A systematic

In the article titled, “Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial” published in pages 134-144, issue 2, vol. 8 of Chronic Diseases and Translational Medicine,¹ the information of trial registration at the end of Abstract is missing. The registration information should be: This study has been registered on www.chinadrugtrials.org.cn, registered number CTR20130079.

In the article titled, “Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open-label, parallel-group, non-inferiority Phase III trail” published in pages 59-70, issue 1, vol. 8 of Chronic Diseases and Translational Medicine,¹ the information of trial registration at the end of Abstract is missing. The registration information should be: This study has been registered on www.chinadrugtrials.org.cn, registered number CTR20130080.

Trial-based economic value of prevention programs for diabetes is inexplicit. We aimed to review the cost-effectiveness of nonpharmacological interventions to prevent type-2 diabetes mellitus (T2DM) for high-risk people. Six electronic databases were searched up to March 2022. Studies assessing both the cost and health outcomes of nonpharmacological interventions for people at high-risk of T2DM were included. The quality of the study was assessed by the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. The primary outcome for synthesis was incremental cost-effectiveness ratios (ICER) for quality-adjusted life years (QALYs), and costs were standardized in 2022 US dollars. Narrative synthesis was performed, considering different types and delivery methods of interventions. Sixteen studies included five based on the US diabetes prevention program (DPP), six on non-DPP-based lifestyle interventions, four on health education, and one on screening plus lifestyle intervention. Compared with usual care, lifestyle interventions showed higher potential of cost-effectiveness than educational interventions. Among lifestyle interventions, DPP-based programs were less cost-effective (median of ICERs: $27,077/QALY) than non-DPP-based programs (median of ICERs: $1395/QALY) from healthcare perspectives, but with larger decreases in diabetes incidence. Besides, the cost-effectiveness of interventions was more possibly realized through the combination of different delivery methods. Different interventions to prevent T2DM in high-risk populations are both cost-effective and feasible in various settings. Nevertheless, economic evidence from low- and middle-income countries is still lacking, and interventions delivered by trained laypersons and combined with peer support sessions or mobile technologies could be potentially a cost-effective solution in such settings with limited resources.