Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension.

BACKGROUND:There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension.METHODS:The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD.RESULTS:During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association.CONCLUSIONS:NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.

Effects of intensive blood pressure lowering in patients with diabetes: A pooled analysis of the STEP and ACCORD-BP randomized trials.

AIM:To determine whether intensive systolic blood pressure (SBP) lowering can benefit hypertensive patients with diabetes.MATERIALS AND METHODS:We performed a pooled analysis of individual patient data from two randomized trials to compare intensive and standard SBP targets in hypertensive patients with diabetes (STEP diabetes subgroup and ACCORD-BP standard glycaemic group, n = 1627 and n = 2362, respectively). We defined a modified primary outcome as a composite of stroke, major coronary artery disease (myocardial infarction and unstable angina), heart failure, and cardiovascular death. The secondary outcomes were individual components of the primary outcome and death from any cause. A Cox proportional hazards regression model was used in the main analysis. We conducted one-stage mixed-effect models and two-stage analyses as sensitivity and supplementary analyses to verify the robustness of the findings.RESULTS:A total of 3989 patients were randomized to undergo intensive (n = 1984) or standard SBP treatment (n = 2005). After a median follow-up of 3.83 years, the primary outcome occurred in 193/1984 patients in the intensive group and in 247/2005 patients in the standard group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.64-0.93). The incidence rates for secondary outcomes were lower in the intensive group than in the standard group, but were not significantly different, except for stroke (intensive vs. standard: 32/1984 vs. 58/2005; HR 0.56, 95% CI 0.36-0.86). These results remained consistent in the additional sensitivity and supplementary analyses.CONCLUSIONS:An intensive SBP-lowering target of 110 to <130 mmHg reduces the cardiovascular outcomes compared with a standard SBP-lowering target of 130 to <150 mmHg. The findings of this study support the favourable effects of intensive SBP lowering in hypertensive patients with diabetes.

Alterations of Gut Microbiome, Metabolome, and Lipidome in Takayasu Arteritis.

OBJECTIVE:Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune-related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK.METHODS:To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes.RESULTS:A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK.CONCLUSION:This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome-metagenome interface in TAK subtype prediction and pathogenesis are suggested.

Long-term blood pressure outcomes of laparoscopic adrenalectomy in trHTN patients.

Background and Objectives:Treatment resistant hypertension (trHTN) is a common clinical problem faced by many clinicians. Laparoscopic adrenalectomy effectively trims blood pressure (BP) elevation secondary to various functional adrenal disorders. However, the impact of adrenalectomy on BP within trHTN patients has never been reported. Our present study aims to investigate the effect of adrenalectomy on BP management within trHTN patients, and to explore clinical predictors for postoperative BP normalization.Patients and Methods:In our current study, 117 patients diagnosed with trHTN and performed with unilateral adrenalectomy were consecutively enrolled, demographic and medical information were documented for baseline data collection. BP was measured with a standard electronic sphygmomanometer twice a day. Long-term periodical interview was conducted and 109 (93.2%) enrolled patients were successfully followed-up at an averaged 36.2 months.Results:At follow-up, 27/109 (25%) trHTN patients acquired BP normalization and 68/109 (62%) patients acquired BP improvement. Mean taking anti-hypertensive agents reduced from presurgical 4.24 to present 1.21 (P < 0.01), along with 7.2 mmHg reduction in SBP (P < 0.01). Image macro-adenoma and hypokalemia history were found to be the two strongest predictors for postoperative BP normalization. (χ2= 28.032, P < 0.01). The incidence of adverse postoperative events was quite small.Conclusions:In summary, this current study implicates that adrenalectomy is an efficacious and safe surgical strategy for BP management in trHTN patients. Patients with both unilateral macro-adenoma and hypokalemia are more prone to acquire postoperative BP normalization.

Achieved systolic blood pressure and cardiovascular outcomes in 60-80-year-old patients: the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial.

AIMS:Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, data is missing on patients who had target-achieved (TA). This study aims to show the cardiovascular effect of maintaining SBP at intensive levels.METHODS:The Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial was a multicentre, randomized, controlled trial which enrolled 8511 young-older (60-80 years) hypertensive patients without prior stroke to compare the cardiovascular prognosis of the intensive treatment (SBP target, 110 to <130 mmHg) vs. the standard treatment (130 to <150 mmHg). This secondary analysis assessed data in patients who achieved a mean SBP within target values. The association of mean achieved SBP and cardiovascular events was examined using a cubic spline function.RESULTS:In total, 3053 patients (72.0%) in the intensive-treatment group and 3427 (80.3%) in the standard-treatment group had an SBP target achieved, with mean follow-up SBP values of 124.2 mmHg and 137.4 mmHg, respectively. Throughout the median 3.38-year follow-up, the cardiovascular risk was significantly lower in the TA intensive-treatment group than in the TA standard-treatment group [adjusted hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.80; P < 0.001]. In the intensive-treatment group, patients failing to achieve SBP targets presented higher cardiovascular risk than those TA patients (HR 2.04, 95% CI 1.44-2.88; P < 0.001). A J-shaped relationship was observed between the mean achieved SBP and risk of cardiovascular events, with the lowest risk at an SBP of 126.9 mmHg.CONCLUSIONS:Maintaining SBP at <130 mmHg offers additional cardiovascular benefits among young-older patients with hypertension.REGISTRATION:ClinicalTrials.gov: NCT03015311.

Pre-miRNA Hsa-Let-7a-2: a Novel Intracellular Partner of Angiotensin II Type 2 Receptor Negatively Regulating its Signals.

G protein-coupled receptors (GPCRs) are the largest family of druggable targets, and their biological functions depend on different ligands and intracellular interactomes. Some microRNAs (miRNAs) bind as ligands to RNA-sensitive toll-like receptor 7 to regulate the inflammatory response, thereby contributing to the pathogenesis of cancer or neurodegeneration. It is unknown whether miRNAs bind to angiotensin II (Ang II) type 2 receptor (AGTR2), a critical protective GPCR in cardiovascular diseases, as ligands or intracellular interactomes. Here, screening for miRNAs that bind to AGTR2, we identified and confirmed that the pre-miRNA hsa-let-7a-2 non-competitively binds to the intracellular third loop of AGTR2. Functionally, intracellular hsa-let-7a-2 overexpression suppressed the Ang II-induced AGTR2 effects such as cAMP lowering, RhoA inhibition, and activation of Src homology 2 domain-containing protein-tyrosine phosphatase 1, whereas hsa-let-7a-2 knockdown enhanced these effects. Consistently, overexpressed hsa-let-7a-2 restrained the AGTR2-induced antiproliferation, antimigration, and proapoptosis of cells, and vasodilation of mesenteric arteries. Our findings demonstrated that hsa-let-7a-2 is a novel intracellular partner of AGTR2 that negatively regulates AGTR2-activated signals.

Coronary Intervention Guided by Quantitative Flow Ratio vs Angiography in Patients With or Without Diabetes.

BACKGROUND:The clinical utility of the quantitative flow ratio (QFR), a novel angiography-based index for the functional assessment of coronary stenoses, has recently been demonstrated in patients undergoing percutaneous coronary intervention (PCI).OBJECTIVES:This study aimed to ascertain whether the beneficial outcomes of QFR guidance for lesion selection during PCI is affected by diabetes status.METHODS:This substudy from the FAVOR III China trial, in which diabetes was one of the prespecified factors for stratified randomization, compared clinical outcomes of QFR-guided vs angiography-guided PCI lesion selection according to the presence of diabetes. The primary endpoint was the 1-year risk of major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization).RESULTS:Among 3,825 patients enrolled, 1,295 (33.9%) had diabetes, 347 (26.8%) of whom were treated with insulin. Baseline characteristics were well balanced between treatment arms in both diabetic and nondiabetic patients. Compared with standard angiography-based lesion selection, the QFR-guided strategy consistently reduced the risk of 1-year MACE in both diabetic patients (6.2% vs 9.6%; HR: 0.64; 95% CI: 0.43-0.95) and nondiabetic patients (5.6% vs 8.3%; HR: 0.66; 95% CI: 0.49-0.89) (Pinteraction = 0.88). Among patients in whom PCI was deferred after QFR, the risk of 1-year MACE was similar in patients with and without diabetes (4.5% vs 6.2%; P = 0.51).CONCLUSIONS:A QFR-guided lesion selection strategy improves PCI outcomes compared with standard angiography guidance in patients both with and without diabetes. (The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease [FAVOR III China Study]; NCT03656848).

Improving outcomes for older hypertensive patients: is more intensive treatment better?

INTRODUCTION:With population aging, late-life hypertension is becoming an increasingly important issue. Mounting evidence has documented additional cardiovascular benefits induced by a more intensive target, lower than what are recommended in most current guidelines for systolic blood pressure (SBP) reduction in older patients with hypertension. However, the optimal target remains less clear.AREAS COVERED:In the present review, we summarized the evolution of the perspective into late-life hypertension and the development of the 'optimal' target for SBP reduction in older patients with hypertension. More importantly, new evidence from latest antihypertensive drug-placebo studies, blood pressure target studies, and high-quality meta-analysis regarding the effect of intensive SBP treatment in older patients were covered and discussed in detail.EXPERT OPINION:In summary, robust evidence supports that a SBP target of <130 mmHg is safe and will induce additional cardiovascular benefits in general older patients with hypertension. This benefit seems to be consistent, but less degreed in older patients with comorbidities such as chronic kidney disease or diabetes mellitus. However, such an intensive SBP target should be judiciously applied in older patients under extreme conditions. Collectively, edging down the relaxed SBP targets to <130 mmHg in most of the current guidelines is in imperative need.

Improving outcomes for older hypertensive patients: is more intensive treatment better?

Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure.

Although some co-risk factors and hemodynamic alterations are involved in hypertension progression, their direct biomechanical effects are unclear. Here, we constructed a high-hydrostatic-pressure cell-culture system to imitate constant hypertension and identified novel molecular classifications of human aortic smooth muscle cells (HASMCs) by single-cell transcriptome analysis. Under 100-mmHg (analogous to healthy human blood pressure) or 200-mmHg (analogous to hypertension) hydrostatic pressure for 48 h, HASMCs showed six distinct vascular SMC (VSMC) clusters according to differential gene expression and gene ontology enrichment analysis. Especially, two novel HASMC subsets were identified, named the inflammatory subset, with CXCL2, CXCL3 and CCL2 as markers, and the endothelial-function inhibitory subset, with AKR1C2, AKR1C3, SERPINF1 as markers. The inflammatory subset promoted CXCL2&3 and CCL2 chemokine expression and secretion, triggering monocyte migration; the endothelial-function inhibitory subset secreted SERPINF1 and accelerated prostaglandin F2α generation to inhibit angiogenesis. The expression of the two VSMC subsets was greatly increased in arterial media from patients with hypertension and experimental animal models of hypertension. Collectively, we identified high hydrostatic pressure directly driving VSMCs into two new subsets, promoting or exacerbating endothelial dysfunction, thereby contributing to the pathogenesis of cardiovascular diseases.

Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension.

BACKGROUND:There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension.METHODS:The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD.RESULTS:During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association.CONCLUSIONS:NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.

Effects of intensive blood pressure lowering in patients with diabetes: A pooled analysis of the STEP and ACCORD-BP randomized trials.

AIM:To determine whether intensive systolic blood pressure (SBP) lowering can benefit hypertensive patients with diabetes.MATERIALS AND METHODS:We performed a pooled analysis of individual patient data from two randomized trials to compare intensive and standard SBP targets in hypertensive patients with diabetes (STEP diabetes subgroup and ACCORD-BP standard glycaemic group, n = 1627 and n = 2362, respectively). We defined a modified primary outcome as a composite of stroke, major coronary artery disease (myocardial infarction and unstable angina), heart failure, and cardiovascular death. The secondary outcomes were individual components of the primary outcome and death from any cause. A Cox proportional hazards regression model was used in the main analysis. We conducted one-stage mixed-effect models and two-stage analyses as sensitivity and supplementary analyses to verify the robustness of the findings.RESULTS:A total of 3989 patients were randomized to undergo intensive (n = 1984) or standard SBP treatment (n = 2005). After a median follow-up of 3.83 years, the primary outcome occurred in 193/1984 patients in the intensive group and in 247/2005 patients in the standard group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.64-0.93). The incidence rates for secondary outcomes were lower in the intensive group than in the standard group, but were not significantly different, except for stroke (intensive vs. standard: 32/1984 vs. 58/2005; HR 0.56, 95% CI 0.36-0.86). These results remained consistent in the additional sensitivity and supplementary analyses.CONCLUSIONS:An intensive SBP-lowering target of 110 to <130 mmHg reduces the cardiovascular outcomes compared with a standard SBP-lowering target of 130 to <150 mmHg. The findings of this study support the favourable effects of intensive SBP lowering in hypertensive patients with diabetes.

Alterations of Gut Microbiome, Metabolome, and Lipidome in Takayasu Arteritis.

OBJECTIVE:Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune-related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK.METHODS:To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes.RESULTS:A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK.CONCLUSION:This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome-metagenome interface in TAK subtype prediction and pathogenesis are suggested.

Long-term blood pressure outcomes of laparoscopic adrenalectomy in trHTN patients.

Background and Objectives:Treatment resistant hypertension (trHTN) is a common clinical problem faced by many clinicians. Laparoscopic adrenalectomy effectively trims blood pressure (BP) elevation secondary to various functional adrenal disorders. However, the impact of adrenalectomy on BP within trHTN patients has never been reported. Our present study aims to investigate the effect of adrenalectomy on BP management within trHTN patients, and to explore clinical predictors for postoperative BP normalization.Patients and Methods:In our current study, 117 patients diagnosed with trHTN and performed with unilateral adrenalectomy were consecutively enrolled, demographic and medical information were documented for baseline data collection. BP was measured with a standard electronic sphygmomanometer twice a day. Long-term periodical interview was conducted and 109 (93.2%) enrolled patients were successfully followed-up at an averaged 36.2 months.Results:At follow-up, 27/109 (25%) trHTN patients acquired BP normalization and 68/109 (62%) patients acquired BP improvement. Mean taking anti-hypertensive agents reduced from presurgical 4.24 to present 1.21 (P < 0.01), along with 7.2 mmHg reduction in SBP (P < 0.01). Image macro-adenoma and hypokalemia history were found to be the two strongest predictors for postoperative BP normalization. (χ2= 28.032, P < 0.01). The incidence of adverse postoperative events was quite small.Conclusions:In summary, this current study implicates that adrenalectomy is an efficacious and safe surgical strategy for BP management in trHTN patients. Patients with both unilateral macro-adenoma and hypokalemia are more prone to acquire postoperative BP normalization.

Achieved systolic blood pressure and cardiovascular outcomes in 60-80-year-old patients: the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial.

AIMS:Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, data is missing on patients who had target-achieved (TA). This study aims to show the cardiovascular effect of maintaining SBP at intensive levels.METHODS:The Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial was a multicentre, randomized, controlled trial which enrolled 8511 young-older (60-80 years) hypertensive patients without prior stroke to compare the cardiovascular prognosis of the intensive treatment (SBP target, 110 to <130 mmHg) vs. the standard treatment (130 to <150 mmHg). This secondary analysis assessed data in patients who achieved a mean SBP within target values. The association of mean achieved SBP and cardiovascular events was examined using a cubic spline function.RESULTS:In total, 3053 patients (72.0%) in the intensive-treatment group and 3427 (80.3%) in the standard-treatment group had an SBP target achieved, with mean follow-up SBP values of 124.2 mmHg and 137.4 mmHg, respectively. Throughout the median 3.38-year follow-up, the cardiovascular risk was significantly lower in the TA intensive-treatment group than in the TA standard-treatment group [adjusted hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.80; P < 0.001]. In the intensive-treatment group, patients failing to achieve SBP targets presented higher cardiovascular risk than those TA patients (HR 2.04, 95% CI 1.44-2.88; P < 0.001). A J-shaped relationship was observed between the mean achieved SBP and risk of cardiovascular events, with the lowest risk at an SBP of 126.9 mmHg.CONCLUSIONS:Maintaining SBP at <130 mmHg offers additional cardiovascular benefits among young-older patients with hypertension.REGISTRATION:ClinicalTrials.gov: NCT03015311.

Pre-miRNA Hsa-Let-7a-2: a Novel Intracellular Partner of Angiotensin II Type 2 Receptor Negatively Regulating its Signals.

G protein-coupled receptors (GPCRs) are the largest family of druggable targets, and their biological functions depend on different ligands and intracellular interactomes. Some microRNAs (miRNAs) bind as ligands to RNA-sensitive toll-like receptor 7 to regulate the inflammatory response, thereby contributing to the pathogenesis of cancer or neurodegeneration. It is unknown whether miRNAs bind to angiotensin II (Ang II) type 2 receptor (AGTR2), a critical protective GPCR in cardiovascular diseases, as ligands or intracellular interactomes. Here, screening for miRNAs that bind to AGTR2, we identified and confirmed that the pre-miRNA hsa-let-7a-2 non-competitively binds to the intracellular third loop of AGTR2. Functionally, intracellular hsa-let-7a-2 overexpression suppressed the Ang II-induced AGTR2 effects such as cAMP lowering, RhoA inhibition, and activation of Src homology 2 domain-containing protein-tyrosine phosphatase 1, whereas hsa-let-7a-2 knockdown enhanced these effects. Consistently, overexpressed hsa-let-7a-2 restrained the AGTR2-induced antiproliferation, antimigration, and proapoptosis of cells, and vasodilation of mesenteric arteries. Our findings demonstrated that hsa-let-7a-2 is a novel intracellular partner of AGTR2 that negatively regulates AGTR2-activated signals.

Coronary Intervention Guided by Quantitative Flow Ratio vs Angiography in Patients With or Without Diabetes.

BACKGROUND:The clinical utility of the quantitative flow ratio (QFR), a novel angiography-based index for the functional assessment of coronary stenoses, has recently been demonstrated in patients undergoing percutaneous coronary intervention (PCI).OBJECTIVES:This study aimed to ascertain whether the beneficial outcomes of QFR guidance for lesion selection during PCI is affected by diabetes status.METHODS:This substudy from the FAVOR III China trial, in which diabetes was one of the prespecified factors for stratified randomization, compared clinical outcomes of QFR-guided vs angiography-guided PCI lesion selection according to the presence of diabetes. The primary endpoint was the 1-year risk of major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization).RESULTS:Among 3,825 patients enrolled, 1,295 (33.9%) had diabetes, 347 (26.8%) of whom were treated with insulin. Baseline characteristics were well balanced between treatment arms in both diabetic and nondiabetic patients. Compared with standard angiography-based lesion selection, the QFR-guided strategy consistently reduced the risk of 1-year MACE in both diabetic patients (6.2% vs 9.6%; HR: 0.64; 95% CI: 0.43-0.95) and nondiabetic patients (5.6% vs 8.3%; HR: 0.66; 95% CI: 0.49-0.89) (Pinteraction = 0.88). Among patients in whom PCI was deferred after QFR, the risk of 1-year MACE was similar in patients with and without diabetes (4.5% vs 6.2%; P = 0.51).CONCLUSIONS:A QFR-guided lesion selection strategy improves PCI outcomes compared with standard angiography guidance in patients both with and without diabetes. (The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease [FAVOR III China Study]; NCT03656848).

Improving outcomes for older hypertensive patients: is more intensive treatment better?

INTRODUCTION:With population aging, late-life hypertension is becoming an increasingly important issue. Mounting evidence has documented additional cardiovascular benefits induced by a more intensive target, lower than what are recommended in most current guidelines for systolic blood pressure (SBP) reduction in older patients with hypertension. However, the optimal target remains less clear.AREAS COVERED:In the present review, we summarized the evolution of the perspective into late-life hypertension and the development of the 'optimal' target for SBP reduction in older patients with hypertension. More importantly, new evidence from latest antihypertensive drug-placebo studies, blood pressure target studies, and high-quality meta-analysis regarding the effect of intensive SBP treatment in older patients were covered and discussed in detail.EXPERT OPINION:In summary, robust evidence supports that a SBP target of <130 mmHg is safe and will induce additional cardiovascular benefits in general older patients with hypertension. This benefit seems to be consistent, but less degreed in older patients with comorbidities such as chronic kidney disease or diabetes mellitus. However, such an intensive SBP target should be judiciously applied in older patients under extreme conditions. Collectively, edging down the relaxed SBP targets to <130 mmHg in most of the current guidelines is in imperative need.

Improving outcomes for older hypertensive patients: is more intensive treatment better?

Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure.

Although some co-risk factors and hemodynamic alterations are involved in hypertension progression, their direct biomechanical effects are unclear. Here, we constructed a high-hydrostatic-pressure cell-culture system to imitate constant hypertension and identified novel molecular classifications of human aortic smooth muscle cells (HASMCs) by single-cell transcriptome analysis. Under 100-mmHg (analogous to healthy human blood pressure) or 200-mmHg (analogous to hypertension) hydrostatic pressure for 48 h, HASMCs showed six distinct vascular SMC (VSMC) clusters according to differential gene expression and gene ontology enrichment analysis. Especially, two novel HASMC subsets were identified, named the inflammatory subset, with CXCL2, CXCL3 and CCL2 as markers, and the endothelial-function inhibitory subset, with AKR1C2, AKR1C3, SERPINF1 as markers. The inflammatory subset promoted CXCL2&3 and CCL2 chemokine expression and secretion, triggering monocyte migration; the endothelial-function inhibitory subset secreted SERPINF1 and accelerated prostaglandin F2α generation to inhibit angiogenesis. The expression of the two VSMC subsets was greatly increased in arterial media from patients with hypertension and experimental animal models of hypertension. Collectively, we identified high hydrostatic pressure directly driving VSMCs into two new subsets, promoting or exacerbating endothelial dysfunction, thereby contributing to the pathogenesis of cardiovascular diseases.