Comparison of Influence of Blood Pressure and Carotid-Femoral Pulse Wave Velocity on Target Organ Damage in Hypertension.

Objectives: Assessment of target organ damage (TOD) is an important part of the diagnosis and evaluation of hypertension. Carotid-femoral pulse wave velocity (cf-PWV) is considered to be the gold-standard for noninvasive arterial stiffness assessment. This study aims to analyze the risk of TOD in people with different phenotypes of peripheral blood pressure and cf-PWV. Methods: The study cohort was recruited from December 2017 to September 2021 at Ruijin Hospital in Shanghai. It was divided into 4 groups according to peripheral blood pressure (pBP) and cf-PWV. TOD was assessed as carotid intima-media thickness (CIMT), chronic kidney disease (CKD), urinary albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI). Results: A total of 1,257 subjects (mean age 53.13 ± 12.65 years, 64.2% males) was recruited. Age, body mass index (BMI) and fasting blood glucose (FBG), as well as peripheral systolic blood pressure (pSBP), peripheral diastolic blood pressure (pDBP), peripheral pulse pressure (pPP) were significantly different in the four groups (P < 0.01). eGFR, ACR, LVMI and CIMT were significantly different among different groups (P < 0.01). The risk of ACR abnormality was significantly higher in the group with elevated pBP (P = 0.005, OR 2.264, 95%CI 1.277-4.016; and in the group with elevated pBP and cf-PWV (P = 0.003, OR 1.482, 95%CI 1.144-1.920), while left ventricular hypertrophy (LVH) was significantly higher in the group with elevated cf-PWV (P = 0.002, OR 1.868, 95%CI 1.249-2.793). Conclusion: Different profiles based on the status of PBP and cf-PWV associated with different TOD. Individuals with higher pBP have an increased risk of ACR abnormality, while individuals with only cf-PWV elevated have a higher risk of LVH.

Comparison of Risk of Target Organ Damage in Different Phenotypes of Arterial Stiffness and Central Aortic Blood Pressure.

Objectives: The aim of this study was to explore the risk of target organ damage (TOD) in different groups based on carotid-femoral pulse wave velocity (cfPWV) and central aortic blood pressure (CBP) in different populations. Methods: The study cohort was divided into four groups according to the status of cfPWV and CBP [Group (cfPWV/CBP): high cfPWV and high CBP; Group (cfPWV): high cfPWV and normal CBP; Group (CBP): normal cfPWV and high CBP; Group (control): normal cfPWV and normal CBP]. TOD was determined by the assessment of carotid intima-media thickness (CIMT) abnormality, chronic kidney disease (CKD), microalbuminuria, and left ventricular hypertrophy (LVH). Results: A total of 1,280 patients (mean age 53.14 ± 12.76 years, 64.1% male patients) were recruited in this study. Regarding Group (control) as reference, LVH was significantly higher in Group (cfPWV) and Group (CBP) [OR 2.406, 95% CI (1.301-4.452), P < 0.05; OR 2.007, 95% CI (1.335-3.017), P < 0.05]; microalbuminuria was significantly higher in Group (cfPWV/CBP) and Group (CBP) [OR 3.219, 95% CI (1.630-6.359), P < 0.05; OR 3.156, 95% CI (1.961-5.079), P < 0.05]. With age stratified by 60 years, the risk of CKD was significantly higher in Group (cfPWV/CBP) [OR 4.019, 95% CI (1.439-11.229), P < 0.05]. Conclusion: Different phenotypes based on the status of cfPWV and CBP were associated with different TOD. Individuals with both cfPWV and CBP elevated have a higher risk of microalbuminuria.

Disparate Associations of 24-h Central Aortic and Brachial Cuff Blood Pressure With Hypertension-Mediated Organ Damage and Cardiovascular Risk.

Objective: Aim of this study was to evaluate the associations of non-invasive central aortic and peripheral (brachial) blood pressure (BP) for Hypertension-mediated organ damage (HMOD) and atherosclerotic cardiovascular disease (ASCVD) risk. Methods: We evaluated associations of HMOD with 24-h ambulatory blood pressure monitoring (ABPM) of central aortic and peripheral BP indices in patients with primary hypertension and presence of several cardiovascular risk factors. BP measurements were performed by means of a non-invasive automated oscillometric device (Mobil-O-Graph). HMOD was defined as the presence of carotid intima-media thickness (IMT) above normal values and/or carotid plaque, left ventricular hypertrophy (LVH), and/or renal abnormalities as assessed by urine albumin/creatinine ratio above normal values and/or estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Results: In the study cohort of 273 (age 55.2 ± 13.4 years, 71.8% male) patients with primary hypertension, documented HMOD was present in 180 (65.9%), LVH in 70 (25.6%), increased IMT in 129 (47.3%). Fifty-six patients (20.5%) had kidney organ damage (20.5% albuminuria and 2.6% impaired eGFR). When accounting for confounding factors (age, sex, body-mass-index, antihypertensive treatment, smoking, triacylglycerol, statin treatment, glucose, hypoglycemic therapy, or heart rate) only peripheral 24-h pulse pressure (PP) maintained statistical significance with HMOD indices (OR: 1.126, 95% CI: 1.012~1.253; p = 0.029). Using ASCVD risk score as the independent continuous variable in multiple linear regression, 24-h central systolic pressure (SBP) (ß = 0.179; 95% CI:0.019~0.387; p = 0.031), daytime central PP (ß = 0.114; 95% CI:0.070~0.375; p = 0.005, night-time central SBP (ß = 0.411; 95% CI:0.112~0.691; p = 0.007) and night-time PP (ß = 0.257; 95% CI:0.165~0.780; p = 0.003) were all positively associated with ASCVD risk. Conclusions: Blood pressure obtained by 24-h ABPM was better correlated with HMOD than office BP. Whilst 24-h peripheral BP showed a stronger association with HMOD than 24-h central BP, the prognostic value of 24-h central BP for the 10-year ASCVD risk was superior to 24-h peripheral BP.

Female Gender Is Associated with Higher Susceptibility of Weight Induced Arterial Stiffening and Rise in Blood Pressure.

Arterial stiffness is an important predictor of cardiovascular events, independent of traditional risk factors. Stiffening of arteries, though an adaptive process to hemodynamic load, results in substantial increase in the pulsatile hemodynamic forces that detrimentally affects the microcirculation perfusing the vital organs such as the brain, heart and kidneys. Studies have proposed that arterial stiffness precedes and may contribute to the development of hypertension in individuals with obesity. Our study sought to determine the gender-based effects on arterial stiffening in obesity which may predispose to the development of hypertension. We found female sex is associated with higher susceptibility of weight-related arterial stiffening and rise in blood pressure in obesity. Women had significantly higher carotid-femoral pulse wave velocity (CF-PWV) with higher body mass index (BMI) status (normal: 7.9 ± 2 m/s; overweight: 9.1 ± 2 m/s; obese: 9 ± 2 m/s, p < 0.001), whereas it was similar in males across all BMI categories. The linear association between arterial stiffness and BMI following adjustment for age and brachial systolic and diastolic blood pressure (BP), remained significant in females (ß = 0.06; 95% CI 0.01 to 0.1; p < 0.05) but not in males (ß = 0.04; 95% CI -0.01 to 0.1; p > 0.05). The mean CF-PWV values increased by 0.1 m/s for every 1 kg/m2 increase in BMI in the female subjects in the age adjusted linear model, while such effect was not seen in the male subjects. In line with arterial stiffening, the overweight and obese females demonstrated significantly higher systolic brachial BP. (BP difference: ΔBP 9-11 mmHg, p < 0.01) and central systolic pressure (ΔBP 8-10 mmHg, p < 0.05) compared to their lean counterparts, unlike the male subjects. Our results suggest that female gender is associated with higher susceptibility of weight-related arterial stiffening and rise in blood pressure.

Niemann-Pick type C1 regulates cholesterol transport and metamorphosis in silkworm, Bombyx mori (Dazao).

NPC1 is a large glycoprotein with 13 transmembrane-spanning domains, which plays a crucial biological role in cholesterol transport and metamorphosis of animals. However, the physiological functions of this gene have rarely been elucidated in insects. Here, we isolated the NPC1 gene from Bombyx mori (BmNPC1), sequenced and evaluated its physiological functions. BmNPC1 comprised of 3702 bp open reading frame, encoding a protein of 1233 amino acid residues. The recombinant protein was expressed, and anti-BmNPC1 antibodies were synthesized. Immunofluorescence assay revealed that BmNPC1 protein localized in the cytoplasm of the cells. The qRT-PCR analysis showed that BmNPC1 expression was most significant in the testis, followed by the malpighian tubules, hemocytes, and ovary. The knockdown of BmNPC1 by double-stranded RNA caused the accumulation of cholesterol in the cells. Furthermore, suppression of this gene influenced the expression of ecdysone-responsive genes and also prevented the molting in B. mori (Dazao) larvae. Overall, BmNPC1 may have different biological roles in the physiology of silkworm, B. mori (Dazao), since it regulates the cholesterol transport and molting process.

Impact of new hypertension guidelines on target organ damage screening in a Shanghai community-dwelling population.

Recently, the 2017 ACC/AHA released new hypertension guidelines and proposed a redefinition of hypertension from 140/90 to 130/80 mm Hg. This study assesses the impact of the lower threshold for hypertension diagnosis on the association of hypertension with target organ damage (TOD). Health checks were conducted in a community-dwelling population in Shanghai in 2017 (N = 10 826; 43.26% mean, age 62 ± 12 years [range 29-95 years]). Subclinical TOD indices were quantified in terms of left ventricular hypertrophy (LVH) by electrocardiogram (Sokolow-Lyon standard), estimated glomerular filtration rate (eGFR), and presence of proteinuria. Information on clinical TOD was obtained by questionnaire. Arteriosclerotic cardiovascular disease (ASCVD) was determined by the 2013 ACC/ AHA recommended guidelines. Compared to the higher threshold (140/90 mm Hg), the lower threshold (130/80 mm Hg) was associated with variable rates of increased detection of hypertension and TOD: (a) Hypertension: incidence of hypertension, 29.5% (51.8%-81.5%) increase in persons with hypertension if the threshold of 130/80 mm Hg is used; (b) Subclinical TOD: LVH, 20.8%; eGFR (30-60 mL/min per 1.73 m2 ), 23.7%; proteinuria, 23.5%; (c) Clinical TOD: chronic kidney disease (CKD) IV (eGFR＜30 mL/min per 1.73 m2 ), 3.1%; diabetes (fasting glucose ≥7.0 mmol/L or HbA1C＞7.0%), 24.3%; stroke, 26.4%; chronic heart disease, 28.1%; acute myocardial infarction, 19.5% (69.4% to 88.9% of total of 36); ASCVD ≥10%, 29.3%. The lower threshold was associated with a significantly higher detection rate of clinical and subclinical TOD of approximately 20% compared to the higher threshold. 15%-20% of TOD and 29% of ASCVD were also found below the lower threshold of hypertension.

Molecular cloning, characterization and expression analysis of cathepsin O in silkworm Bombyx mori related to bacterial response.

Cathepsins are the main members of the cysteine family and play important roles in immune response in vertebrates. The Cathepsin O of Bombyx mori (BmCathepsin O) was cloned from the hemocytes by the rapid amplification of cDNA ends (RACE). The genomic DNA was 6131bp long with a total of six exons and five introns. Its pre-mRNA was spliced to generate two spliceosomes. By comparisons with other reported cathepsins O, it was concluded that the identity between them ranged from 29 to 39%. Expression analysis indicated that BmCathepsin O was specific-expressed in hemocytes, and highly expressed at the 4th molting and metamorphosis stages. Immunofluorescence assay and qRT-PCR showed that BmCathepsin O was expressed in granulocytes and plasmatocytes. Interestingly, BmCathepsin O was significantly up-regulated after stimulated by 20-hydroxyecdysone (20-E) in vivo, which suggested that BmCathepsin O may be regulated by 20E. Moreover, activation of BmCathepsin O was also observed in hemocytes challenged by Escherichia coli, indicating its potential involvement in the innate immune system of silkworm, B. mori. In summary, our studies provide a new insight into the functional features of Cathepsin O.