Targeting the Efficacy of Intensive Blood Pressure Treatment in Hypertensive Patients　- An Exploratory Analysis of SPRINT.

BACKGROUND: Hypertensive patients show highly heterogeneous treatment effects (HTEs) and cardiovascular prognosis, and not all benefit from intensive blood pressure treatment.Methods and Results: We used the causal forest model to identify potential HTEs of patients in the Systolic Blood Pressure Intervention Trial (SPRINT). Cox regression was performed to assess hazard ratios (HRs) for cardiovascular disease (CVD) outcomes and to compare the effects of intensive treatment among groups. The model revealed 3 representative covariates and patients were partitioned into 4 subgroups: Group 1 (baseline body mass index [BMI] ≤28.32 kg/m2and estimated glomerular filtration rate [eGFR] ≤69.53 mL/min/1.73 m2); Group 2 (baseline BMI ≤28.32 kg/m2and eGFR >69.53 mL/min/1.73 m2); Group 3 (baseline BMI >28.32 kg/m2and 10-year CVD risk ≤15.8%); Group 4 (baseline BMI >28.32 kg/m2and 10-year CVD risk >15.8%). Intensive treatment was shown to be beneficial only in Group 2 (HR 0.54, 95% confidence interval [CI] 0.35-0.82; P=0.004) and Group 4 (HR 0.69, 95% CI 0.52-0.91; P=0.009). CONCLUSIONS: Intensive treatment was effective for patients with high BMI and 10-year CVD risk, or low BMI and normal eGFR, but not for those with low BMI and eGFR, or high BMI and low 10-year CVD risk. Our study could facilitate the categorization of hypertensive patients, ensuring individualized therapy.

Global distribution of zoonotic digenetic trematodes: a scoping review.

BACKGROUND: Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes. METHODS: We conducted a scoping review by searching PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang databases for articles, reviews, and case reports of zoonotic digenetic trematodes, without any restrictions on the year of publication. We followed the inclusion and exclusion criteria to identify relevant studies. And relevant information of the identified studies were collected and summarized. RESULTS: We identified a total of 470 articles that met the inclusion criteria and were included in the review finally. Our analysis revealed the prevalence and global distribution of species in Schistosoma, Echinostoma, Isthmiophora, Echinochasmus, Paragonimus, Opisthorchiidae, Fasciolidae, Heterophyidae, and Eurytrema. Although some flukes are distributed worldwide, developing countries in Asia and Africa are still the most prevalent areas. Furthermore, there were some overlaps between the distribution of zoonotic digenetic trematodes from the same genus, and the prevalence of some zoonotic digenetic trematodes was not entirely consistent with their global distribution. The temporal disparities in zoonotic digenetic trematodes may attribute to the environmental changes. The gaps in our knowledge of the epidemiology and control of zoonotic digenetic trematodes indicate the need for large cohort studies in most countries. CONCLUSIONS: This review provides important insights into the prevalence and global distribution of some zoonotic digenetic trematodes, firstly reveals spatio-temporal disparities in these digenetic trematodes. Countries with higher prevalence rate could be potential sources of transmitting diseases to other areas and are threat for possible outbreaks in the future. Therefore, continued global efforts to control and prevent human trematodiosis, and more international collaborations are necessary in the future.

Targeting efficacy of spironolactone in patients with heart failure with preserved ejection fraction: the TOPCAT study.

AIMS: We aimed to explore the heterogeneous treatment effects (HTEs) for spironolactone treatment in patients with Heart failure with preserved ejection fraction (HFpEF) and examine the efficacy and safety of spironolactone medication, ensuring a better individualized therapy. METHODS AND RESULTS: We used the causal forest algorithm to discover the heterogeneous treatment effects (HTEs) from patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Cox regressions were performed to assess the hazard ratios (HRs) of spironolactone medication for cardiovascular death and drug discontinuation in each group. The causal forest model revealed three representative covariates and participants were partitioned into four subgroups which were Group 1 (baseline BMI ≤ 31.71 kg/m2 and baseline ALP ≤ 80 U/L, n = 759); Group 2 (BMI ≤ 31.71 kg/m2 and ALP > 80 U/L, n = 1088); Group 3 (BMI > 31.71 kg/m2 , and WBC ≤ 6.6 cells/µL, n = 633); Group 4 (BMI > 31.71 kg/m2 and WBC > 6.6 cells/µL, n = 832), respectively. In the four subgroups, spironolactone therapy reduced the risk of cardiovascular death in high-risk group (Group 4) with both high BMI and WBC count (HR: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in low-risk group (Group 1) with both low BMI and ALP (HR: 1.45; 95% CI 1.02 to 2.07; P = 0.041; P for interaction = 0.020) but showed similar risk of drug discontinuation (P for interaction = 0.498). CONCLUSION: Our study manifested the HTEs of spironolactone in patients with HFpEF. Spironolactone treatment in HFpEF patients is feasible and effective in patients with high BMI and WBC while harmful in patients with low BMI and ALP. Machine learning model could be meaningful for improved categorization of patients with HFpEF, ensuring a better individualized therapy in the clinical setting.

Visceral adiposity index and the risk of heart failure, late-life cardiac structure, and function in ARIC study.

BACKGROUND: It is well established that obesity is associated with the risk of heart failure (HF). However, the data about relationship between visceral fat and the risk of HF are limited. AIMS: We aim to evaluate the association between visceral obesity assessed by visceral adiposity index (VAI) and incident HF and left ventricular (LV) structure and function in Atherosclerosis Risk in Communities (ARIC) study. METHODS: We included 12 161 participants (aged 54.1 ± 5.8 years) free of history of HF and coronary heart disease at baseline (1987-89) in ARIC study. We used multivariable Cox hazard regression models to assess the association between the VAI and incident HF. We further explored the effects of the VAI on LV geometry and function among 4817 participants with echocardiographic data using multivariable linear regression analysis and multinomial logistic regression. RESULTS: During a median follow-up of 22.5 years, a total of 1904 (15.7%) participants developed HF. After adjustment for traditional HF risk factors, 1 unit increase in the baseline VAI was associated with an 8% higher risk of incident HF [hazard ratio (HR): 1.08, 95% confidence interval (CI): 1.06-1.11]. Results were similar when participants were categorized by VAI tertiles. Compared with participants in the lowest tertile of VAI, those in the second tertile and third tertile had a greater risk of incident HF [HR (95% CI): 1.19 (1.05-1.34) and 1.42 (1.26-1.61), respectively]. For the analyses of the HF subtypes, the higher VAI was only associated with the risk of HF with preserved ejection fraction, not with HF with reduced ejection fraction. In addition, the greater VAI was associated with worse LV diastolic function and abnormal LV geometry including concentric remodelling, concentric hypertrophy, and eccentric hypertrophy. CONCLUSION: This study shows that higher VAI was independently associated with the increased risk of incident HF and abnormal LV geometry and LV diastolic dysfunction.

We investigated the relationship between visceral adiposity index (VAI) and incident heart failure (HF) in 12 161 participants and further evaluated the possible effect of the VAI on late-life left ventricular (LV) structure and function in 4817 participants who underwent echocardiography examination at Visit 5 in Atherosclerosis Risk in Communities study.Our study found that VAI, a simple alternative indicator of visceral obesity, was positively associated with the risk of HF.Our results shown that VAI was significantly associated with abnormal LV geometry and worse LV diastolic function in late life.