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Introduction: Mounting evidence has indicated that maternal dyslipidemia is associated with adverse obstetric outcomes, and the actions of lipid-lowering drugs in pregnant women remain controversial. Hence, this study aimed to appraise the causal relationship of lipid-lowering drugs [hydroxymethylglutaryl-coenzyme reductase (HMGCR) inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors] with pregnancy and perinatal outcomes using drug-targeting Mendelian randomization analysis., Methods: As a proxy for lipid-lowering drug exposure, two genetic instruments were used: genetic variants within or near the gene linked to low-density lipoprotein cholesterol (LDL-C) and the expression of quantitative trait loci of the drug target gene. Effect estimates were calculated using the inverse variance weighting (IVW) method and summary data-based Mendelian randomization (SMR) method. Heterogeneity and pleiotropy were assessed by Mendelian randomization-Egger regression, the Cochran Q test, and MR-PRESSO analysis., Results: HMGCR inhibitors were ascribed to a reduced risk of preeclampsia in both the IVW-MR method [odds ratio (OR) 0.583; 95% confidence interval (CI) 0.418-0.812; P  = 0.001] and SMR analysis (OR 0.816; 95% CI 0.675-0.986; P  = 0.036). The causal link between HMGCR inhibitors and offspring birthweight was statistically significant only in the analysis using the IVW method (OR, 0.879; 95% CI, 0.788-0.980; P  = 0.020), and the combined results of the OR values supported the potential inhibitory effect of HMGCR inhibitors on offspring birthweight. Causal associations between lipid-lowering drugs and gestational diabetes, preterm birth, and congenital anomalies were not detected in either analysis., Conclusion: No causal associations were observed between lipid-lowering drugs and gestational diabetes, preterm birth or congenital anomalies, whereas genetically predicted HMGCR inhibition dramatically reduced the risk of preeclampsia but attenuated offspring birthweight., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Secondary hypertension has emerged as a major public health problem in China. Early diagnosis and treatment can significantly improve the clinical outcomes. However, data on the current cause composition in China are seldom reported., Objective: To describe the trends in cause-related comorbidities in hospitalized patients with secondary hypertension in China from 2013 to 2016., Methods: This was a retrospective analysis based on the national Hospital Quality Monitoring System (HQMS) database, which collects information from the front pages of in-hospital medical records. Hospitalized patients with secondary hypertension from 746 tertiary hospitals that consistently uploaded data to the HQMS from 2013 to 2016 were enrolled. All diagnoses were identified using International Classification of Diseases version 10 (ICD-10) diagnostic codes. Descriptive analyses were used to determine the proportions of secondary hypertension causes and changing trends over 4 years., Result: The study collected data on 402 371 hospitalized patients with secondary hypertension from the HQMS during 2013-2016. Secondary hypertension caused by renal parenchymal disease ranked first and accounted for more than 50%. Obstructive sleep apnea syndrome (OSAS) followed closely with a rate of approximately 25%. Primary aldosteronism presented the highest proportion among all causes of endocrine hypertension. Regarding longitudinal changes over time, the rates of renal hypertension showed a significant downward trend from 2013 to 2016 (P < 0.001). In contrast, OSAS, endocrine hypertension, renal vascular disease, and aorta diseases maintained a significant upward trend from 2013 to 2016 (P < 0.001). The rates of these diseases in women with common secondary hypertension was higher than that of men, except in patients with OSAS (P < 0.001). In addition, renal parenchymal diseases and renal vascular diseases gradually decreased with age, whereas OSAS and aortic diseases gradually increased with age. The proportion of endocrine hypertension in the middle-aged group was higher than the other two age groups., Conclusion: The study provides important information on the changing trends of cause rate of secondary hypertension modified by age and sex in China during 2013-2016. Renal parenchymal disease is still the most common cause of secondary hypertension with a decreasing trend, followed by OSAS with an increasing trend., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: We aimed to explore the relationship of hypertensive retinopathy with carotid intima--media thickness (CIMT), and to examine the possible effect modifiers in Chinese adults with hypertension., Methods: We conducted a cross-sectional study of 12 342 hypertensive patients with complete exit site visit data from the China Stroke Primary Prevention Trial. CIMT was measured by carotid ultrasonography. Hypertensive retinopathy was diagnosed according to the Keith--Wagener--Barker classification., Results: The mean (SD) CIMT among study participants was 739.9 (111.4) μm. Compared with patients with grade 1 hypertensive retinopathy or without hypertensive retinopathy, a significantly higher CIMT level (β, 7.63, 95% CI: 2.54--12.73) was observed in patients with grade 2-4 hypertensive retinopathy. Moreover, the association between hypertensive retinopathy (grade 2-4 versus grade 1 or normal) and CIMT was stronger in participants of younger age (<60 years; β, 13.70, 95% CI: 5.65--21.75; versus ≥60 years; β, 1.03, 95% CI: -5.58 to 7.63; P interaction = 0.006); or with lower total homocysteine levels [<12.1 μmol/l (median); β, 12.70, 95% CI: 5.98--19.42; versus ≥12.1 μmol/l; β, 2.07, 95% CI: -5.63 to 9.78; P interaction = 0.030). None of the other variables, including sex, BMI, study centers, treatment group, SBP, triglycerides, total cholesterol, fasting blood glucose, folate, serum creatinine, current smoking and alcohol drinking, significantly modified the relation of hypertensive retinopathy with CIMT levels., Conclusion: Hypertensive retinopathy (grade 2 and higher) was significantly associated with increased CIMT in hypertensive patients. The association was stronger in those of younger age or with lower total homocysteine levels.

Objective: Data on the association between visit-to-visit variability (VVV) in blood pressure (BP) and the risk of stroke among hypertensive patients with chronic kidney disease (CKD) is limited. We aimed to evaluate the relation of VVV in BP with the risk of stroke, and examine any possible effect modifiers in hypertensive patients with mild-to-moderate CKD., Methods: This is a post-hoc analysis of the China Stroke Primary Prevention Trial. A total of 3091 patients with estimated glomerular filtration rate 30-60 ml/min per 1.73 m and/or proteinuria at baseline, without occurring stroke and with BP measurements of at least two visits from randomization to the 12-month visit were included. The main VVV in BP was expressed as SD. The primary outcome was first stroke., Results: The median subsequent treatment duration was 3.7 years. After multivariable adjustment, including baseline SBP and mean SBP during the first 12-month follow-up, there was a significantly positive relationship of SD SBP with the risk of subsequent first stroke (per SD increment; odds ratio, 1.41; 95% confidence interval: 1.17-1.69) and first ischemic stroke (odds ratio, 1.55; 95% confidence interval: 1.26-1.90). Results were consistent across various subgroups, including age, sex, baseline SBP, treatment compliance, and mean SBP, concomitant usage of calcium channel blocker during the first 12-month follow-up period. Similar trends were also found for coefficient of variation SBP, and SD or coefficient of variation DBP. However, there was no significant association between BP variability and first hemorrhagic stroke., Conclusion: In hypertensive adults with mild-to-moderate CKD, visit-to-visit variability in BP was significantly associated with the risk of subsequent first stroke.

Objective: We aimed to investigate the relationship of BMI and waist circumference with the development of chronic kidney disease (CKD)., Methods: A total of 12 672 hypertensive patients with estimated glomerular filtration rate (eGFR) at least 60 ml/min per 1.73 m from the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT) were included. The primary outcome was the development of CKD, defined as a decrease in eGFR of at least 30% and to a level of less than 60 ml/min per 1.73 m at the exit visit, or end-stage renal disease. A secondary outcome was rapid renal function decline, defined as an average decline in eGFR of at least 5 ml/min/1.73 m per year., Results: Over a median follow-up of 4.4 years, the risk of the primary event (per 1 kg/m increment; OR = 1.07, 95% CI 1.02-1.14) or rapid renal function decline (per 1 kg/m increment; OR = 1.05, 95% CI 1.01-1.08) increased with each increment of BMI. Consistently, compared with those with normal weight (BMI <24.0 kg/m), participants with obesity (BMI ≥28.0 kg/m) had an increased risk of the primary event (OR = 1.82; 95% CI 1.15-2.90) and rapid renal function decline (OR = 1.26; 95% CI 0.95-1.67). However, waist circumference had no obvious effect on the risk of the primary event (per 5 cm increment: OR = 0.94, 95% CI 0.85-1.04) or rapid renal function decline (OR = 0.96, 95% CI 0.90-1.03)., Conclusion: Higher BMI, but not waist circumference, was significantly associated with an increased risk of CKD development in hypertensive patients with normal kidney function.

Objective: We aimed to evaluate whether proteinuria and estimated glomerular filtration rate (eGFR) levels can modify the efficacy of folic acid therapy on the risk of all-cause mortality among hypertensive patients in the China Stroke Primary Prevention Trial, a randomized, double-blind, and controlled trial., Methods: A total of 20 702 hypertensive patients without a history of major cardiovascular diseases were randomly assigned to a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n = 10 348), or 10-mg enalapril alone (n = 10 354). All-cause mortality, a prespecified endpoint of the China Stroke Primary Prevention Trial, was the main outcome in this analysis., Results: Over a median treatment duration of 4.5 years, in the enalapril alone group, both heavy proteinuria [vs. absent, 10.8 vs. 2.7%; hazard ratio = 3.30; 95% confidence interval (CI): 2.10-5.18] and lower eGFR levels (<60 vs. ≥90 ml/min per 1.73 m, 13.0 vs. 2.2%; hazard ratio = 1.93; 95% CI: 1.19-3.12) were significantly associated with increased risk of all-cause mortality. Folic acid supplementation significantly reduced the risk of all-cause mortality in patients with heavy proteinuria (6.4% in the enalapril-folic acid vs. 10.8% in the enalapril alone group, hazard ratio = 0.49; 95% CI: 0.26-0.94), but not in those with absent or mild proteinuria (2.8 vs. 2.9%, hazard ratio = 0.99; 95% CI: 0.84-1.17; P for interaction = 0.040). However, eGFR levels did not significantly modify the effect of folic acid supplementation in reducing the risk of all-cause mortality (P for interaction = 0.228)., Conclusion: Among hypertensive patients without a history of major cardiovascular diseases, folic acid therapy could reduce the mortality risk associated with heavy proteinuria.