Cardiovascular Risk Reduction Research Articles

Differential Effects of Two Isocaloric Healthy Diets on Postprandial Lipid Responses in Individuals with Type 2 Diabetes.

High blood concentrations of triglycerides (TG) in the postprandial period have been shown to be more closely associated with the risk of cardiovascular disease (CVD) than fasting values in individuals with type 2 diabetes (T2D). Dietary changes are the primary determinants of postprandial lipid responses. We investigated the effects of an isocaloric multifactorial diet, rich in n-3 PUFA, MUFA, fiber, polyphenols, and vitamins, compared to an isocaloric diet, containing the same amount of MUFA, on the postprandial lipid response in T2D individuals. Following a randomized, controlled, parallel group design, 43 (25 male/18 female) T2D individuals were assigned to an isocaloric multifactorial (n = 21) or a MUFA-rich diet (n = 22). At the beginning and after the 8 weeks of dietary intervention, the concentrations of plasma triglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol were detected at fasting and over a 4-h test meal with the same composition as the prescribed diet. The concentrations of fasting plasma triglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol did not change after both diets. Compared with the MUFA diet, the 8-week multifactorial diet significantly lowered the postprandial response, which was evaluated as the incremental area under the curve (iAUC), of triglycerides by 33% (64 ± 68 vs. 96 ± 50 mmol/L·240 min, mean ± SD, respectively, p = 0.018), total cholesterol by 105% (-51 ± 33 vs. -25 ± 29, p = 0.013), and non-HDL cholesterol by 206% (-39 ± 33 vs. -13 ± 23, p = 0.013). In T2D individuals, a multifactorial diet, characterized by several beneficial components, improved the postprandial lipid response compared to a MUFA diet, generally considered a healthy diet being reduced in saturated fat, and probably contributed to the reduction of cardiovascular risk.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study

BackgroundThe residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.MethodsData on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.ResultsThe 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.ConclusionThis study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Intermediate versus morning chronotype has lower vascular insulin sensitivity in adults with obesity.

Chronotype reflects a circadian rhythmicity that regulates endothelial function. While the morning chronotype (MORN) usually has low cardiovascular disease risk, no study has examined insulin action on endothelial function between chronotypes. We hypothesized intermediate chronotypes (INT) would have lower vascular insulin sensitivity than morning chronotype (MORN). Adults with obesity were classified per Morningness-Eveningness Questionnaire (MEQ) as either MORN (n = 27, 22 female, MEQ = 63.7 ± 4.7, 53.8 ± 6.7 years, 35.3 ± 4.9 kg/m2) or INT (n = 29, 23 female, MEQ = 48.8 ± 6.7, 56.6 ± 9.0 years, 35.7 ± 6.1 kg/m2). A 120 min euglycaemic-hyperinsulinaemic clamp (40 mU/m2/min, 90 mg/dl) was conducted to assess macrovascular insulin sensitivity via brachial artery flow-mediated dilation (%FMD; conduit artery), post-ischaemic flow velocity (resistance arteriole), as well as microvascular insulin sensitivity via contrast-enhanced ultrasound [e.g. microvascular blood volume (perfusion)]. Fasting plasma arginine and citrulline, as well as fasting and clamp-derived plasma endothelin-1 and nitrate/nitrite, were assessed as surrogates of vasoconstriction and nitric oxide-mediated vasodilation. Aerobic fitness (VO2max) and body composition (dual-energy X-ray absorptiometry) were also collected. MORN had a higher VO2max compared with INT (p < .01), although there was no difference in fat mass. While fasting FMD was similar between groups, insulin lowered FMD corrected to shear stress and microvascular blood volume in INT compared with MORN after co-varying for VO2max (both p ≤ .02). INT also had a lower fasting nitrate (p = .03) and arginine (p = .07). Higher MEQ correlated with elevated FMD (r = 0.33, p = .03) and lower post-ischaemic flow velocity (r = -0.33, p = .03) as well as shear rate (r = -0.36, p = .02) at 120 min. When measured during the morning, INT had a lower vascular insulin sensitivity than MORN. Additional work is needed to understand endothelial function differences among chronotypes to optimize cardiovascular disease risk reduction.

Rivaroxaban and Dabigatran: prospects for use in the management of heart failure

Scientific articles examine the effectiveness and pharmacokinetics of two oral anticoagulants, dabigatran and rivaroxaban, in the context of treating atrial fibrillation and chronic heart failure. Dabigatran, as a direct thrombin inhibitor, influences the thrombin zone and fibrinogen, preventing fibrin formation. Rivaroxaban, as a selective factor Xa inhibitor, blocks factor X activation. Both medications demonstrate high bioavailability and plasma protein binding. Studies on the efficacy of rivaroxaban in atherosclerosis and low-dose rivaroxaban in chronic heart failure did not reveal statistically significant reductions in cardiovascular risk. The findings emphasize the importance of further research and an individualized approach to selecting anticoagulants for optimal management of patients with diverse cardiovascular conditions.

Influence of Repeated Plaque Visualization on Cardiovascular Risk Reduction after 3 years; a randomized controlled trial.

Helping people to understand their cardiovascular (CV) risk can influence the choices they make for risk reduction, including medication adherence and lifestyle modification. This study sought whether repeated visualization of coronary artery calcium (CAC) images was effective in sustaining long-term risk control in primary prevention, independent of a risk reduction program. Asymptomatic, statin-naïve participants, 40-70 years, with a family history of premature coronary artery disease and a CAC score from 1-400 were randomised to a nurse-led CV risk reduction program or standard care with bi-annual reviews. Only the intervention group (220 of 449 participants) visualised their CAC image (with repeat exposure in the first 3 months) and were initiated on statin therapy. The primary outcome was change in Framingham Risk Score (FRS) at 36 months, and the impact of CAC image recall on CV risk was assessed. The reduction in FRS (difference in differences (DID): -3.4% [95%CI: -4.4% to -2.4%], p=<0.001 and low-density-lipoprotein-cholesterol -1.2mmol/L [95%CI: -1.4 to -1.0], p=<0.001)) over 36 months was greater in the intervention than the control group. Within the intervention group, sustained recall of CAC images at 24 months was associated with lower systolic blood pressure (DID -4.3mmHg [95%CI: -7.7 to-0.9], p=0.01) and waist circumference (DID -2.0cm [95% CI: -3.9 to -0.1], p=0.03) at 36 months compared to unsustained recall. A nurse-led program, combining personalized patient visualization of CAC imaging with statin therapy, is beneficial for improving CV risk. Recalling the presentation of CAC images through repeated visual exposure may influence risk reduction.

Dietary Salt Restriction and Adherence to the Mediterranean Diet: A Single Way to Reduce Cardiovascular Risk?

The dietary restriction of salt intake and the adhesion to Mediterranean dietary patterns are among the most recommended lifestyle modifications for the prevention of cardiovascular diseases. A large amount of evidence supports these recommendations; indeed, several studies show that a higher adherence to Mediterranean dietary patterns is associated with a reduced risk of cardiovascular disease. Likewise, findings from observational and clinical studies suggest a causal role of excess salt intake in blood pressure increase, cardiovascular organ damage, and the incidence of cardiovascular diseases. In this context, it is also conceivable that the beneficial effects of these two dietary patterns overlap because Mediterranean dietary patterns are typically characterized by a large consumption of plant-based foods with low sodium content. However, there is little data on this issue, and heterogeneous results are available on the relationship between adherence to salt restriction and to Mediterranean dietary patterns. Thus, this short review focuses on the epidemiological and clinical evidence of the relationship between the adherence to Mediterranean dietary patterns and dietary salt restriction in the context of cardiovascular risk.

Albuminuria: An Underappreciated Risk Factor for Cardiovascular Disease.

Albuminuria, an established biomarker of the progression of chronic kidney disease, is also recognized as a biomarker for the risk of cardiovascular disease. Elevated urinary albumin excretion indicates kidney damage and systemic vascular disease, including myocardial capillary disease and arterial stiffness. Albuminuria is associated with an increased risk of coronary artery disease, stroke, heart failure, arrhythmias, and microvascular disease. There are now several therapeutic agents that can lead to albuminuria lowering and a reduction in cardiovascular risk. However, screening for albuminuria is still low. Considering the importance of multidisciplinary management of patients with cardiovascular disease, it is crucial that health care professionals managing such patients are aware of the benefits of albuminuria surveillance and management.

Association of European Paediatric and Congenital Cardiology practical recommendations for surveillance and prevention of cardiac disease in childhood cancer survivors: the importance of physical activity and lifestyle changes From the Association of European Paediatric and Congenital Cardiology Working Group Sports Cardiology, Physical Activity and Prevention, Working Group Adult Congenital Heart Disease, Working Group Imaging and Working Group Heart Failure.

Childhood cancer survivors are at increased risk of developing cardiovascular diseases, presenting as the main causes of morbidity and mortality within this group. Besides the usual primary and secondary prevention in combination with screening during follow-up, the modifiable lifestyle factors of physical activity, nutrition, and body weight have not yet gained enough attention regarding potential cardiovascular risk reduction. These practical recommendations aim to provide summarised information and practical implications to paediatricians and health professionals treating childhood cancer survivors to reduce the risk of cardiovascular late effects. The content derives from either published guidelines or expert opinions from Association of European Paediatric and Congenital Cardiology working groups and is in accordance with current state-of-the-art. All usual methods of prevention and screening regarding the risk, monitoring, and treatment of occurring cardiovascular diseases are summarised. Additionally, modifiable lifestyle factors are explained, and clear practical implications are named. Modifiable lifestyle factors should definitely be considered as a cost-effective and complementary approach to already implemented follow-up care programs in cardio-oncology, which can be actively addressed by the survivors themselves. However, treating physicians are strongly encouraged to support survivors to develop and maintain a healthy lifestyle, including physical activity as one of the major influencing factors. This article summarises relevant background information and provides specific practical recommendations on how to advise survivors to increase their level of physical activity.

Tailored risk assessment and forecasting in intermittent claudication.

Guidelines recommend cardiovascular risk reduction and supervised exercise therapy as the first line of treatment in intermittent claudication, but implementation challenges and poor patient compliance lead to significant variation in management and therefore outcomes. The development of a precise risk stratification tool is proposed through a machine-learning algorithm that aims to provide personalized outcome predictions for different management strategies. Feature selection was performed using the least absolute shrinkage and selection operator method. The model was developed using a bootstrapped sample based on patients with intermittent claudication from a vascular centre to predict chronic limb-threatening ischaemia, two or more revascularization procedures, major adverse cardiovascular events, and major adverse limb events. Algorithm performance was evaluated using the area under the receiver operating characteristic curve. Calibration curves were generated to assess the consistency between predicted and actual outcomes. Decision curve analysis was employed to evaluate the clinical utility. Validation was performed using a similar dataset. The bootstrapped sample of 10 000 patients was based on 255 patients. The model was validated using a similar sample of 254 patients. The area under the receiver operating characteristic curves for risk of progression to chronic limb-threatening ischaemia at 2 years (0.892), risk of progression to chronic limb-threatening ischaemia at 5 years (0.866), likelihood of major adverse cardiovascular events within 5 years (0.836), likelihood of major adverse limb events within 5 years (0.891), and likelihood of two or more revascularization procedures within 5 years (0.896) demonstrated excellent discrimination. Calibration curves demonstrated good consistency between predicted and actual outcomes and decision curve analysis confirmed clinical utility. Logistic regression yielded slightly lower area under the receiver operating characteristic curves for these outcomes compared with the least absolute shrinkage and selection operator algorithm (0.728, 0.717, 0.746, 0.756, and 0.733 respectively). External calibration curve and decision curve analysis confirmed the reliability and clinical utility of the model, surpassing traditional logistic regression. The machine-learning algorithm successfully predicts outcomes for patients with intermittent claudication across various initial treatment strategies, offering potential for improved risk stratification and patient outcomes.

Semaglutide and Tirzepatide Use and Reduction of Cardiovascular Risks in Adults with Overweight and Obesity

Background: Obesity is a prevalent, growing health concern in the United States, affecting over 42% of adults and contributing significantly to the burden of cardiovascular disease (CVD). Recently, approved anti-obesity medications (AOMs) such as semaglutide (Wegovy) and tirzepatide (Zepbound) have emerged as potential interventions to reduce weight and potentially lower cardiovascular risk among individuals with obesity. Aim: To analyze the impact of AOM on cardiovascular risk among US patients with obesity. Methods: Utilizing Kythera data, we conducted a retrospective cohort study from November 2022 to June 2024. Patients with obesity and AOM use were identified based on diagnosis claims and prescription claims for tirzepatide or semaglutide (identification period: Nov. 1, 2023–Dec. 31, 2023) with 6 months of follow-up to measure CVD risk. Exclusions included patients with pre-existing CVD and prior AOM use. Cox regression and multivariable analyses adjusted for comorbidities and sociodemographic factors were employed to assess the risk of cardiovascular events, with additional analyses comparing outcomes between tirzepatide and semaglutide users. Results: We identified 22,620 patients with obesity and AOM use and 84,427 patients with obesity without AOM use. Significant differences were observed in the proportion of patients with an Elixhauser Index Score ≥2, comprising 61.97% in the AOM cohort versus 13.50% in the non-AOM cohort (standardized difference = 1.2868). The AOM cohort demonstrated significantly lower incidence of cardiovascular events (1.77%) than non-AOM users (12.17%, p&lt;0.0001). Adjusted analyses confirmed that AOM use was associated with a substantially reduced risk of CVD (hazard ratio=0.37, p&lt;0.0001). Differences in specific cardiovascular outcomes between tirzepatide and semaglutide users were observed, with semaglutide users showing a higher hazard of CVD than tirzepatide users (hazard ratio=1.53, p=0.0215). Conclusions: Use of AOM was associated with a significantly lower risk-adjusted likelihood of cardiovascular events than non-use, highlighting these medications as promising interventions in obesity management.

Effects of SGLT2 Inhibitors Compared with Sulfonylurea on Glycaemic Control and Cardiovascular Risk Reduction in Asia: Meta-Analysis

Effects of SGLT2 Inhibitors Compared with Sulfonylurea on Glycaemic Control and Cardiovascular Risk Reduction in Asia: Meta-Analysis

MORTALITY AND CARDIOVASCULAR RISK REDUCTION AFTER REVERSION OF PREDIABETES TO NORMOGLYCEMIA: A SYSTEMATIC REVIEW.

It is unclear whether reversion to normoglycemia decreases overall cardiovascular events and all-cause mortality risk in the long term. We aim to investigate the magnitude of change in cardiovascular risk and mortality in patients who reverted from a prediabetes state. Three electronic databases, including PubMed, Proquest, and EBSCOHost databases, were utilized. A manual hand search of articles was also done. We selected studies that measure cardiovascular risk and all-cause mortality risk after reversion from prediabetes to normoglycemia. The following terms and its variant were used in the search strategy: 'reversion,' 'prediabetes,' 'normoglycemia,' cardiovascular risk,' and 'mortality.' Seven studies with a total of 73,845 participants were obtained. Most studies suggest that reversion of prediabetes reduced the cardiovascular and all-cause mortality risk (RR: 0.50 - 0.78) compared to persistent prediabetes state or progression to diabetes with long-term follow-up ranging from 5 to 12 years, while two studies did not show significant association in CVD and all-cause morality risk. Although there were mixed results regarding if prediabetes poses a higher risk than normoglycemia for cardiovascular events and all-cause mortality, measures to normalize blood glucose for prediabetes should still be advocated.

Correction to: Eligibility for Cardiovascular Risk Reduction Therapy in the U.S. Based on SELECT Trial Criteria: Insights from the National Health and Nutrition Examination Survey.

Correction to: Eligibility for Cardiovascular Risk Reduction Therapy in the U.S. Based on SELECT Trial Criteria: Insights from the National Health and Nutrition Examination Survey.

A Structured Community Health Screening Program and Impact on Patient Lifestyle Changes for Cardiovascular Risk Reduction

A Structured Community Health Screening Program and Impact on Patient Lifestyle Changes for Cardiovascular Risk Reduction

Risk Stratification and Treatment of Obesity for Primary and Secondary Prevention of Cardiovascular Disease.

In this review, we discuss contemporary and emerging approaches for risk stratification and management of excess adiposity for the primary and secondary prevention of cardiovascular disease. Obesity is simultaneously a pandemic-scale disease and major risk factor for the incidence and progression of a wide range of cardiometabolic conditions, but risk stratification and treatment remain clinically challenging. However, sex-, race-, and ethnicity-sensitive anthropometric measures, body composition-focused imaging, and health burden-centric staging systems have emerged as important facilitators of holistic risk prediction. Further, expanding therapeutic approaches, including comprehensive lifestyle programs, anti-obesity pharmacotherapies, device/endoscopy-based interventions, metabolic surgery, and novel healthcare delivery resources offer new empowerment for cardiovascular risk reduction in individuals with obesity. Personalized risk stratification and weight management are central to reducing the lifetime prevalence and impact of cardiovascular disease. Further evidence informing long-term safety, efficacy, and cost-effectiveness of novel approaches targeting obesity are critically needed.

THE RELATIONSHIP BETWEEN NEIGHBORHOOD INFRASTRUCTURE AND RISK FACTORS IN PATIENTS WITH MYOCARDIAL INFARCTION

HighlightsThe analysis of associations between the elements of the neighboughood area infrastructure and cardiovascular risk factors was performed in a high-risk population of patients with myocardial infarction. This analysis has practical importance for the comprehensive optimization of local preventive approaches. Aim. To study the association of the neighborhood infrastructure parameters with cardiovascular risk factors in patients with myocardial infarction (MI).Material and Methods. The study included 150 patients with MI. On the basis of their subjective opinion expressed by the Neighborhood Environmental Walkability Scale questionnaire, the infrastructure of the area of residence was analyzed, and its favorable and unfavorable parameters were identified. Cardiovascular risk factors were identified based on the survey and medical records.Results. Among all patients with MI, the risk of arterial hypertension with MI was reduced by the presence of a dividing dirt strip in the vicinity of OR 0.32 (95% CI 0.12; 0.83) and accessible public transport OR 0.32 (95% CI 0.10; 0.95), dyslipidemia – the remote location of the restaurant OR 0.50 (95% CI 0.26; 0.97) and the place of work OR 0.32 (95% CI 0.12; 0.86), smoking – distance from a public transport stop OR 0.20 (95% CI 0.04; 0.94) and proximity to a restaurant OR 0.50 (95% CI 0.26; 0.97), physical inactivity – distance from work OR 0.08 (95% CI 0.01; 0.76), stress – remote location of a clothing store OR 0.45 (95% CI 0.22; 0.93), alcohol consumption – compliance of the living area with the conditions necessary for raising children OR 0.27 (95% CI 0.07; 0.97), insufficient consumption of fresh fruits and vegetables – remote location of a pharmacy OR 0.18 (95% CI 0.03; 0.97), the lack of dividing ground strip OR 0.10 (95% CI 0.01; 0.91) and the presence of garbage in the vicinity of OR 0.08 (95% CI 0.01; 0.53), patient satisfaction with the compliance of the living area with the conditions necessary for the upbringing of children OR 0.10 (95% CI 0.01; 0.70). Inadequate street lighting at night contributed to an increased risk of dyslipidemia, OR 3.05 (95% CI 1.04; 8.92), alcohol consumption – proximity to a clothing store OR 2.23 (95% CI 1.08; 4.57).In citizens with MI, a decrease in the risk of arterial hypertension was associated with the presence of a dividing dirt strip in the vicinity of OSH 0.17 (95% CI 0.06; 0.49) and accessible public transport OSH 0.19 (95% CI 0.05; 0.65); stress – with the absence of alternative routes in the vicinity of OSH 0.27 (95% CI 0.09; 0.79); the risk of insufficient consumption of fresh fruits and vegetables – with the distance of the pharmacy OR 0.18 (95% CI 0.03; 0.96), the absence of a dividing dirt strip OR 0.07 (95% CI 0.01; 0.63) and sidewalks in the vicinity of OR 0.14 (95% CI 0.02; 0.89). In rural patients with MI, the risk of stress decreased with the presence of sidewalks in the vicinity of OR 0.21 (95% CI 0.05; 0.99) and accessible public transport OR 0.15 (95% CI 0.03; 0.85).Conclusion. The identification of unfavorable parameters of the territory of residence in patients with MI should contribute to the formation of the concept of a health-preserving environment necessary for further reduction of cardiovascular risks of MI in the population.

Awareness of Hypertension in Reproductive-Aged Women Living With Chronic Kidney Disease

BackgroundHypertension is the most important modifiable cardiovascular risk factor among women. Chronic kidney disease (CKD), which affects 1 in 10 reproductive-aged women, increases the risk of hypertension; however, awareness of hypertension in this population is unknown. This study aimed to determine hypertension awareness among reproductive-aged women living with chronic kidney disease. MethodsWomen aged 18 to 50 years with CKD were recruited from nephrology clinics in Calgary, Alberta, Canada. Participants completed a semistructured interview and focused chart review, serum and urine laboratory assessment, and a physical examination that included anthropomorphic measurements and 2 automated office blood pressure readings. Hypertension was defined according to the use of ≥ 1 antihypertensive medications and/or an automated office blood pressure reading of ≥ 135/85 mm Hg. Data were stratified by hypertension status, as well as by awareness, and descriptively presented as mean ± standard deviation, numerical values, and percentages. ResultsSixty-three participants with CKD were included. Thirty-eight (60%) participants had hypertension according to study definitions. Of those with hypertension, 30 participants (79%) were aware of their hypertension status. ConclusionsHypertension awareness is relatively high in reproductive-aged women living with CKD. However, hypertension awareness is the critical component for hypertension management, and further work is necessary to optimize reduction of cardiovascular risk in this important population.

Potential Long-Term Benefit of Home Systolic Blood Pressure Below 125 mm Hg for Cardiovascular Risk Reduction: The J-HOP Study Extended.

The long-term benefit of achieving the Japanese Society of Hypertension home systolic blood pressure (SBP) target of <125 mm Hg has not been fully evaluated. This study investigated the long-term risk of cardiovascular disease events in individuals with home SBP <125 versus 125 to <135 or ≥135 mm Hg who participated in the J-HOP study (Japan Morning Surge-Home Blood Pressure). The J-HOP study enrolled outpatients with ≥1 cardiovascular risk factor between 2005 and 2012, with follow-up until March 2015 and extended follow-up from December 2017 to May 2018. Cardiovascular disease events (stroke, coronary artery disease, congestive heart failure, and aortic dissection) were compared between home SBP subgroups. During mean 5.9 years of follow-up in 4231 participants (mean age, 65 years), cardiovascular events included stroke (n=89), coronary artery disease (n=116), congestive heart failure (n=37), and aortic dissection (n=8). The adjusted 10-year risk of total cardiovascular disease was slightly higher, and stroke risk was significantly higher when baseline home SBP was ≥135 versus <125 mm Hg (adjusted hazard ratio, 1.39 [95% CI, 0.97-2.00] for overall cardiovascular disease and 2.68 [95% CI, 1.34-5.38] for stroke; this was largely due to between-group differences in the first 5 years of follow-up, which were maintained over the subsequent 5 years). Findings were similar in the subgroup of high-risk patients (those with diabetes or stroke history). These data highlight the potential long-term benefit of strict home SBP control and validate this as an appropriate Japanese Society of Hypertension guideline target although confirmation in larger populations is needed. URL: https://www.umin.ac.jp/ctr/; University Hospital Medical Information Network Clinical Trials Registry; Unique identifier: UMIN000000894 (Japan Morning Surge-Home Blood Pressure study).

The benefits of GLP1 receptors in cardiovascular diseases.

Glucagon like peptide-1 (GLP-1) receptor agonists are well established drugs for the treatment of type 2 diabetes (T2D). In addition to glycemic control, GLP-1 receptor agonists have beneficial other effects. They act by binding to GLP-1 receptors, which are widely distributed in the body, including cardiomyocytes and blood vessels. The aim of this article is to provide a comprehensive review of GLP-1 receptor agonists impact on cardiovascular outcomes and risk reduction. In the last decade, several cardiovascular outcomes trials (CVOT) have been conducted in order to explore cardiovascular benefit of GLP-1 receptor agonists. CVOTs primarily proved cardiovascular safety and tolerability of different GLP-1 receptor agonists, but also showed cardiovascular benefit of specific drugs. CVOTs have shown that GLP-1 receptor agonists reduce MACE in patients with T2D compared to placebo. In addition, they have positive impact on several cardiovascular risk factors such as obesity by promoting weight loss, blood pressure and blood lipid levels. Also, they stimulate the endothelium to produce nitric oxide, reduce oxidative stress, and have antiatherogenic and antiinflammatory effects. Studies have shown their positive impact on kidney outcomes in patients with T2D compared to placebo. The results of previous trials are encouraging in terms of multiple positive effects of GLP-1 receptor agonists. However, further research is needed to understand their full potential and all details of their mechanism of action, which will enable to expand the therapeutic indications and to determine their optimal use in clinical practice.

Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear. The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials. Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic. In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01). PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.