Atherosclerosis is a pathologic process occurring within the artery, in which many cell types, including T cell, macrophages, endothelial cells, and smooth muscle cells, interact, and cause chronic ...inflammation, in response to various inner- or outer-cellular stimuli. Atherosclerosis is characterized by a complex interaction of inflammation, lipid deposition, vascular smooth muscle cell proliferation, endothelial dysfunction, and extracellular matrix remodeling, which will result in the formation of an intimal plaque. Although the regulation and function of vascular smooth muscle cells are important in the progression of atherosclerosis, the roles of smooth muscle cells in regulating vascular inflammation are rarely focused upon, compared to those of endothelial cells or inflammatory cells. Therefore, in this review, we will discuss here how smooth muscle cells contribute or regulate the inflammatory reaction in the progression of atherosclerosis, especially in the context of the activation of various membrane receptors, and how they may regulate vascular inflammation.
BACKGROUND:Little is known regarding health outcomes associated with isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), or systolic and diastolic hypertension (SDH) among ...young adults with stage 1 hypertension, defined using the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline.
METHODS:From a nationwide health screening database, we included 6 424 090 participants, aged 20 to 39 years, who were not taking antihypertensive medication at the baseline examination in 2003 to 2007. Participants were categorized as having normal BP (untreated systolic BP SBP <120/diastolic BP DBP <80 mm Hg; n=2 665 310); elevated BP (SBP 120–129/DBP <80 mm Hg; n=705 344); stage 1 IDH (SBP <130/DBP 80–89 mm Hg; n=1 271 505); stage 1 ISH (SBP 130–139/DBP <80 mm Hg; n=255 588); stage 1 SDH (SBP 130–139/DBP 80–89 mm Hg; n=711 503); and stage 2 hypertension (SBP ≥140, DBP ≥90 mm Hg; n=814 840). The primary outcome was composite cardiovascular disease (CVD) events, including myocardial infarction, stroke, heart failure, and CVD-related death.
RESULTS:The median age of the participants was 30 years and 60.9% were male. Over a median follow-up of 13.2 years, 44 070 new CVD events occurred. With normal BP as the reference, multivariable-adjusted hazard ratios (95% CIs) for CVD events were 1.14 (1.09–1.18) for elevated BP, 1.32 (1.28–1.36) for stage 1 IDH, 1.36 (1.29–1.43) for stage 1 ISH, 1.67 (1.61–1.72) for stage 1 SDH, and 2.40 (2.33–2.47) for stage 2 hypertension.
CONCLUSIONS:Among young adults, stage 1 ISH, IDH, and SDH were all associated with higher CVD risks than normal BP. The CVD risks of stage 1 ISH and IDH were similar to each other but lower than the risk of stage 1 SDH. Categorizing young adults with stage 1 hypertension further into stage 1 ISH, IDH, and SDH may improve risk stratification for identifying high-risk individuals.
Recent changes in American and European guidelines on the management of arterial hypertension have caused a considerable shift in the landscape of hypertension management. The 2017 American College ...of Cardiology/American Heart Association/American Society of Hypertension guideline recommends an office visit blood pressure (BP) > 130/80 mmHg as the new threshold for diagnosis of hypertension, and states that the treatment goal for all hypertensive patients should be lowered to < 130/80 mmHg. In contrast, the 2018 European guideline maintains the diagnostic threshold of hypertension at 140/90 mmHg. However, despite their differences in thresholds for diagnosis of hypertension, both guidelines are in agreement that treatment should be considered in patients with BPs in the range of 130 to 139/80 to 89 mmHg if they have high cardiovascular risk. The results from the Systolic Blood Pressure Intervention Trial (SPRINT) study and recent meta-analyses suggest that BP lowering with antihypertensive treatment may be beneficial in reducing cardiovascular event rates in subjects with high-normal BP or stage 1 hypertension according to the new American guideline. However, intensive BP lowering is associated with increased incidence of treatment-associated adverse events, and evidence suggests that BP lowering below 120/70 mmHg increases the risk of cardiovascular events. In this review, we discuss the evidence supporting antihypertensive treatment in subjects with high-normal BP and discuss the specific subgroup of subjects that might benefit from BP lowering.
Increased arterial stiffness is an independent predictor of cardiovascular disease independent from blood pressure. Recent studies have shed new light on the importance of inflammation on the ...pathogenesis of arterial stiffness. Arterial stiffness is associated with the increased activity of angiotensin II, which results in increased NADPH oxidase activity, reduced NO bioavailability and increased production of reactive oxygen species. Angiotensin II signaling activates matrix metalloproteinases (MMPs) which degrade TGFβ precursors to produce active TGFβ, which then results in increased arterial fibrosis. Angiotensin II signaling also activates cytokines, including monocyte chemoattractant protein-1, TNF-α, interleukin-1, interleukin-17 and interleukin- 6. There is also ample clinical evidence that demonstrates the association of inflammation with increased arterial stiffness. Recent studies have shown that reductions in inflammation can reduce arterial stiffness. In patients with rheumatoid arthritis, increased aortic pulse wave velocity in patients was significantly reduced by anti tumor necrosis factor-α therapy. Among the major classes of anti hypertensive drugs, drugs that block the activation of the RAS system may be more effective in reducing the progression of arterial stiffness. Thus, there is rationale for targeting specific inflammatory pathways involved in arterial stiffness in the development of future drugs. Understanding the role of inflammation in the pathogenesis of arterial stiffness is important to understanding the complex puzzle that is the pathophysiology of arterial stiffening and may be important for future development of novel treatments.
Lipid metabolites and cytokines, including chemokines and growth factors, are the key regulators of immune cell function and differentiation, and thus, dysregulation of these regulators is associated ...with various human diseases. However, previous studies demonstrating a positive correlation of cytokine levels with aging may have been influenced by various environmental factors and underlying diseases. Also, data regarding cytokine profiling in the elderly are limited to a small subset of cytokines.
We compared the profiles of 22 cytokines, including chemokines and growth factors, in a case-controlled study group of a gender-matched, healthy cohort of 55 patients over the age of 65 and 55 patients under the age of 45. Assessment of serum cytokine concentrations was performed using commercially-available multiplex bead-based sandwich immunoassays.
Soluble CD40 ligand (sCD40L) and transforming growth factor alpha (TGF-α) levels were significantly higher in the elderly patients, whereas granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly lower in the elderly patients. The partial correlation analysis demonstrating the correlation between cytokine levels when controlled for gender, systolic blood pressure, total cholesterol, HDL cholesterol, triglyceride, and serum creatinine levels further demonstrated that G-CSF, GM-CSF, and MCP-1 had significant negative correlations with age, whereas sCD40L and TGF-α had significant positive correlations.
Future studies will focus on examining the significance of these age-related changes in circulating cytokines and other biological markers and their potential contribution to the development of different age-associated diseases.
Sacubitril/valsartan is superior to enalapril in reducing the risks of cardiovascular death and preventing hospitalization in patients with heart failure and reduced ejection fraction (HFrEF). ...However, patients often do not receive sacubitril/valsartan because of concerns about hypotension. We examined the feasibility of initiating sacubitril/valsartan at a very low dose (VLD) in potentially intolerant patients with HFrEF and subsequent dose up-titration, treatment persistence and outcomes. We analyzed 206 patients with HFrEF grouped according to starting sacubitril/valsartan dose. The VLD group (n = 106) commenced 25 mg twice daily, and the standard-dose (SD) group (n = 100) started on ≥ 50 mg twice daily. Baseline systolic blood pressure was 103 ± 12 mmHg vs. 119 ± 14 mmHg in the SD group (P < 0.001). The maximal target dose achievement rate was higher in the SD group (27.0% vs 9.4%, p = 0.001) and the VLD group experienced more dose up-titrations and fewer down-titrations than the SD group. The VLD group had a decrease in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) similar to the SD group and a similar increase in left ventricular ejection fraction. There were no significant differences in symptomatic hypotension, worsening renal function, hyperkalemia, cardiovascular mortality, and rehospitalization due to HF between the two groups during follow-up period. In patients considered by the treating physician likely to be intolerant of sacubitril/valsartan, initiation with 25 mg twice daily was generally possible and patients remained in therapy, with similar decreases in NT-proBNP and increases in left ventricular ejection fraction to those observed in patients receiving SD sacubitril/valsartan.
It is well known that cold weather is associated with increased risk of myocardial infarction and stroke. It is also well known that colder weather increases blood pressure while warmer weather ...lowers blood pressure. This may have clinical significance as global warming is resulting in increase in average temperature in the Asia/Pacific region. Long term, climate change may have a significant impact on the epidemiology of of hypertension and cardiovascular disease. In this talk, we will discuss how ambient temperature influences seasonal variation of BP and how they may impact the management strategy for patients with hypertension.
Hypertension is an important public health issue because of its association with a number of significant diseases and adverse outcomes. However, there are important ethnic differences in the ...pathogenesis and cardio‐/cerebrovascular consequences of hypertension. Given the large populations and rapidly aging demographic in Asian regions, optimal strategies to diagnose and manage hypertension are of high importance. Ambulatory blood pressure monitoring (ABPM) is an important out‐of‐office blood pressure (BP) measurement tool that should play a central role in hypertension detection and management. The use of ABPM is particularly important in Asia due to the specific features of hypertension in Asian patients, including a high prevalence of masked hypertension, disrupted BP variability with marked morning BP surge, and nocturnal hypertension. This HOPE Asia Network document summarizes region‐specific literature on the relationship between ABPM parameters and cardiovascular risk and target organ damage, providing a rationale for consensus‐based recommendations on the use of ABPM in Asia. The aim of these recommendations is to guide and improve clinical practice to facilitate optimal BP monitoring with the goal of optimizing patient management and expediting the efficient allocation of treatment and health care resources. This should contribute to the HOPE Asia Network mission of improving the management of hypertension and organ protection toward achieving “zero” cardiovascular events in Asia.
Coronary artery calcium (CAC) score is a clinically validated marker of cardiovascular disease risk. We developed and validated a novel cardiovascular risk stratification system based on ...deep-learning-predicted CAC from retinal photographs.
We used 216 152 retinal photographs from five datasets from South Korea, Singapore, and the UK to train and validate the algorithms. First, using one dataset from a South Korean health-screening centre, we trained a deep-learning algorithm to predict the probability of the presence of CAC (ie, deep-learning retinal CAC score, RetiCAC). We stratified RetiCAC scores into tertiles and used Cox proportional hazards models to evaluate the ability of RetiCAC to predict cardiovascular events based on external test sets from South Korea, Singapore, and the UK Biobank. We evaluated the incremental values of RetiCAC when added to the Pooled Cohort Equation (PCE) for participants in the UK Biobank.
RetiCAC outperformed all single clinical parameter models in predicting the presence of CAC (area under the receiver operating characteristic curve of 0·742, 95% CI 0·732–0·753). Among the 527 participants in the South Korean clinical cohort, 33 (6·3%) had cardiovascular events during the 5-year follow-up. When compared with the current CAC risk stratification (0, >0–100, and >100), the three-strata RetiCAC showed comparable prognostic performance with a concordance index of 0·71. In the Singapore population-based cohort (n=8551), 310 (3·6%) participants had fatal cardiovascular events over 10 years, and the three-strata RetiCAC was significantly associated with increased risk of fatal cardiovascular events (hazard ratio HR trend 1·33, 95% CI 1·04–1·71). In the UK Biobank (n=47 679), 337 (0·7%) participants had fatal cardiovascular events over 10 years. When added to the PCE, the three-strata RetiCAC improved cardiovascular risk stratification in the intermediate-risk group (HR trend 1·28, 95% CI 1·07–1·54) and borderline-risk group (1·62, 1·04–2·54), and the continuous net reclassification index was 0·261 (95% CI 0·124–0·364).
A deep learning and retinal photograph-derived CAC score is comparable to CT scan-measured CAC in predicting cardiovascular events, and improves on current risk stratification approaches for cardiovascular disease events. These data suggest retinal photograph-based deep learning has the potential to be used as an alternative measure of CAC, especially in low-resource settings.
Yonsei University College of Medicine; Ministry of Health and Welfare, Korea Institute for Advancement of Technology, South Korea; Agency for Science, Technology, and Research; and National Medical Research Council, Singapore.
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