Interaction of serum vitamin B12 and folate with MTHFR genotypes on risk of ischemic stroke

ObjectiveWe evaluated the interaction of serum folate and vitamin B12 with methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on the risk of first ischemic stroke and on the efficacy of folic acid treatment in prevention of first ischemic stroke.MethodsA total of 20,702 hypertensive adults were randomized to a double-blind treatment of daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. Participants were followed up every 3 months.ResultsMedian values of folate and B12 concentrations at baseline were 8.1 ng/mL and 280.2 pmol/L, respectively. Over a median of 4.5 years, among those not receiving folic acid, participants with baseline serum B12 or serum folate above the median had a significantly lower risk of first ischemic stroke (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.96), especially in those with MTHFR 677 CC genotype (wild-type) (HR, 0.49; 95% CI, 0.31-0.78). Folic acid treatment significantly reduced the risk of first ischemic stroke in participants with both folate and B12 below the median (2.3% in enalapril-folic acid group vs 3.6% in enalapril-only group; HR, 0.62; 95% CI, 0.46-0.86), particularly in MTHFR 677 CC carriers (1.6% vs 4.9%; HR, 0.24; 95% CI, 0.11-0.55). However, TT homozygotes responded better with both folate and B12 levels above the median (HR, 0.28; 95% CI, 0.10-0.75).ConclusionsThe risk of first ischemic stroke was significantly higher in hypertensive patients with low levels of both folate and B12. Effect of folic acid treatment was greatest in patients with low folate and B12 with the CC genotype, and with high folate and B12 with the TT genotype

Folic acid therapy reduces the first stroke risk associated with hypercholesterolemia among hypertensive patients

Background and Purpose - We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. Methods - A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. Results - The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥ 200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (\u3c200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first s roke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84 P\u3c0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024). Conclusions - Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases

Application of Angiotensin Receptor–Neprilysin Inhibitor in Chronic Kidney Disease Patients: Chinese Expert Consensus

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin–angiotensin–aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin–angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD

Effects of allisartan‐isoproxil‐based combination antihypertensive regimen in hypertensive patients with microalbuminuria or hyperuricemia

Abstract Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate the optimal allisartan‐isoproxil‐based combination regimen for hypertensive patients with microalbuminuria or hyperuricemia. A total of 460 hypertensive patients with microalbuminuria and 486 hypertensive patients with hyperuricemia were included in this study. All patients were initially treated with allisartan‐isoproxil for 4 weeks. Thereafter, patients with blood pressure (BP) < 140/90 mmHg continued the monotherapy for 8 weeks; patients with BP ≥140/90 mmHg were randomly assigned in a 1:1 ratio to receive allisartan‐isoproxil + amlodipine (Group A + C) or allisartan‐isoproxil + indapamide (Group A + D) for 8 weeks. The changes of BP, urinary albumin and serum uric acid (UA) were measured. In patients with microalbuminuria, the urinary albumin/creatinine ratio (UACR) significantly decreased by 10.4 mg/g in Group A + C (vs. baseline p = .0035) and 24.2 mg/g in Group A + D (vs baseline p < .0001), intergroup p = NS. In patients with hyperuricemia, serum UA level decreased by 44.5 µmol/L in Group A + C (vs. baseline p = .0003), but increased by 27.2 µmol/L in Group A + D (vs. baseline p = .0167), intergroup p < .0001. The results suggest that for hypertensive patients with microalbuminuria, angiotensin receptor blocker (ARB) + calcium channel blocker (CCB) or ARB+ diuretic both are good choices based on their improvement of microalbuminuria and BP. But for patients with hyperuricemia, ARB + diuretic may further increase the level of UA

From salt to hypertension, what is missed?

Excess salt intake is viewed as a major contributor to hypertension and cardiovascular disease, and dietary salt restriction is broadly recommended by public health guidelines. However, individuals can have widely varying physiological responses to salt intake, and a tailored approach to evaluation and intervention may be needed. The traditional sodium related concepts are challenging to assess clinically for two reasons: (1) spot and 24‐hour urine sodium are frequently used to evaluate salt intake, but are more suitable for population study, and (2) some adverse effects of salt may be blood pressure‐independent. In recent years, previously unknown mechanisms of sodium absorption and storage have been discovered. This review will outline the limitations of current methods to assess sodium balance and discuss new potential evaluation methods and treatment targets.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171252/1/jch14402.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171252/2/jch14402_am.pd

Cesarean scar endometriosis: presentation of 198 cases and literature review

Abstract Background Cesarean scar endometriosis (CSE) is the most common type of abdominal wall endometriosis (AWE). The aim of this study was to systematically identify the clinical features of CSE and recommend precautionary measures. Methods A large, retrospective study was undertaken with CSE patients treated surgically at our hospital between January 2005 and December 2017. Results A total of 198 CSE patients were enrolled, with a mean age of 32.0 ± 4.0 years. The main complaint of the patients was abdominal mass (98.5%), followed by cyclic pain (86.9%). The latency period of CSE was 31.6 ± 23.9 months, and the duration between the onset of symptoms and this surgery was 28.3 ± 25.0 months. A majority (80.8%, n = 160) of the patients had undergone a Pfannenstiel incision, and a minority (19.2%, n = 38) a vertical midline incision. The latency period of CSE in the case of a Pfannenstiel incision was significantly shorter than that in the case of a vertical midline incision (24.0 vs 33.0 months, P = 0.006). A total of 187 (94.4%) patients had a single endometrioma, 11 (5.6%) patients had multiple endometriomas, and the 11 multiple-endometrioma patients had all undergone a Pfannenstiel incision. Lesions of endometrioma were common in corner sites, after either incision: 142/171 (83.0%) in Pfannenstiel incision scars and 32/38 (84.2%) in vertical incision scars. Conclusions The findings of this study indicate that the Pfannenstiel incision carries a higher risk of CSE than the vertical midline incision. Thorough cleaning at the conclusion of CS, particularly of both corner sites of the adipose layer and the fascia layer, is strongly recommended for CSE prevention. Further studies might provide additional recommendations

Comparing an internet-based medical model with a conventional medical model in the management of patients with hypertension in China: Methodology of a cluster randomized study

Background: The awareness, treatment, and control of hypertension are low in China. New and effective management model other than conventional hospital-based practices is needed to optimize the assessment and treatment of hypertension. Objectives: The objective of the study is to design a study that compares blood pressure (BP) control rate in hypertensive patients managed through an internet-based medical model versus conventional medical model. Methods: The study designed is a cluster randomized, unblinded controlled study which will be performed in 14 primary care clinics in Guizhou Province in southwest China. Sites will be randomized to provide BP management services to the patient through an internet-based medical model including home BP monitoring (HBPM) and telemonitoring by primary care physicians, or through a conventional medical model including HBPM and periodical visits to the clinic. Patients aged 45–75 years with two measurements of resting systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg on different days during screening will be enrolled. The primary endpoint is the BP control rate, defined by the percentage of patients achieving target office BP (SBP <140 mmHg and DBP <90 mmHg). Using a superiority design, at least 958 patients were calculated to be sufficient to detect a 10% difference in BP control rate between groups, with a power of 85% and 15% drop out rate. Other outcomes include BP value, BP variability, treatment compliance, medical expense, and treatment satisfaction. Discussion and Conclusion: The results of the trial will be applicable to primary care services in China, especially in the west of China, where medical resources are less readily available. If successful, the internet-based management model with HBPM and telemonitoring from primary care physician may help to improve the BP control in patients in China. Clinical.gov Registration: NCT03527563