Cardiovascular Disease Benefits Research Articles

Abstract 4137914: Eligibility for Semaglutide in US Adults with Diabetes and Potentially Preventable Cardiovascular Events Projected from the SUSTAIN-6 Trial

Background: The Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) trial showed cardiovascular disease (CVD) benefits of semaglutide therapy in patients with type 2 diabetes mellitus (T2DM). Purpose: To estimate the number of US adults with T2DM that may be eligible for semaglutide based on SUSTAIN-6 eligibility criteria and the number of preventable CVD events from semaglutide treatment based on observed CVD event reductions in SUSTAIN-6. Methods: We included US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2011– 2020 who had eligibility criteria from SUSTAIN-6. This included an HbA1c>7.0%, age > 50 with established CVD, heart failure, or chronic kidney disease or an age > 60 with at least one CVD risk factor. We estimated the number of primary composite and secondary CVD endpoints that would occur based on SUSTAIN-6 treated and placebo published event rates, with the difference indicating the number of preventable events (and annualized based on median 2.1 year follow-up time). Results: Among 5002 (projected to 34.0 million [M]) adults we identified with T2DM, we estimated 1,132 (6.9 million) (20.3%) to fit SUSTAIN-6 eligibility criteria. Compared to SUSTAIN-6 trial participants, our sample was slightly older, had a higher proportion of Black participants, shorter duration of diabetes, lower HbA1c and diastolic blood pressure, but similar body mass index and systolic blood pressure. Prior history of ischemic heart disease, myocardial infarction, and stroke were also less common in our NHANES sample. From SUSTAIN-6 semaglutide and placebo primary composite CVD event rates of 6.6% and 8.9%, respectively, we estimated 456,060 and 614,990 events would occur, respectively, for a total of 159,930 preventable CVD events, or 75,681 on an annualized basis. We similarly estimated annualized preventable events for secondary outcomes as shown in the Figure. Conclusion: Semaglutide may prevent many fatal and non-fatal CVD events if provided to US adults meeting SUSTAIN-6 eligibility criteria. More efforts are needed to educate the healthcare providers on the CVD benefits from newer diabetes therapies, including semaglutide.

Managing Gout in Patients with Metabolic Syndrome.

Gout is characterized by monosodium urate (MSU) crystal deposition secondary to hyperuricemia. Gout is associated with metabolic syndrome (MetS) and its related comorbid conditions such as cardiovascular disease (CVD). Major advances have been made in the comprehension of the link between MetS and gout. Despite observational studies suggesting an association between MetS-related conditions and hyperuricemia, there is no proof of causality. Most studies using Mendelian randomization did not find hyperuricemia as a causal factor for MetS-related conditions. In contrast, these conditions were found associated with hyperuricemia, which suggests a reverse causality. Among patients with gout, this high CVD risk profile implies the need for systematic screening for MetS-related conditions. Most international guidelines recommend systematic screening for and care of CVD and related risk factors in patients with gout. Some anti-hypertensive agents, such as losartan and calcium channel blockers, are able to decrease serum urate (SU) levels. However, there are potential interactions between gout management therapies and the treatment of metabolic diseases. Some data suggest that anti-inflammatory drugs used for gout flare treatment, such as colchicine or canakinumab, might have benefits for CVD. Regarding the impact of urate-lowering therapies on CVD risk, recent studies found a similar CVD safety profile for allopurinol and febuxostat. Finally, sodium-glucose cotransporter-2 inhibitors are promising for gout because of their ability to decrease SU levels and risk of recurrent flares. In this review, we focus on the clinical challenge of managing MetS in patients with gout, particularly older patients with co-medications.

Targeting the incretin system in obesity and type 2 diabetes mellitus.

Obesity and type 2 diabetes mellitus (T2DM) are widespread, non-communicable diseases that are responsible for considerable levels of morbidity and mortality globally, primarily in the form of cardiovascular disease (CVD). Changes to lifestyle and behaviour have insufficient long-term efficacy in most patients with these diseases; metabolic surgery, although effective, is not practically deliverable on the scale that is required. Over the past two decades, therapies based on incretin hormones, spearheaded by glucagon-like peptide 1 (GLP1) receptor agonists (GLP1RAs), have become the treatment of choice for obesity and T2DM, and clinical evidence now suggests that these agents have benefits for CVD. We review the latest advances in incretin-based pharmacotherapy. These include 'GLP1 plus' agents, which combine the known advantages of GLP1RAs with the activity of additional hormones, such as glucose-dependent insulinotropic peptide, glucagon and amylin, to achieve desired therapeutic goals. Second-generation non-peptidic oral GLP1RAs promise to extend the benefits of GLP1 therapy to those who do not want, or cannot have, subcutaneous injection therapy. We conclude with a discussion of the knowledge gaps that must be addressed before incretin-based therapies can be properly deployed for maximum benefit in the treatment of obesity and T2DM.

Role of Vitamins in Cardiovascular Health: Know Your Facts-Part 2.

Cardiovascular disease (CVD) is a major cause of morbidity/mortality world-wide, hence preventive interventions are crucial. Observational data showing beneficial CV effects of vitamin supplements, promoted by self-proclaimed experts, have led to ~50% of Americans using multivitamins; this practice has culminated into a multi-billion-dollar business. However, robust evidence is lacking, and certain vitamins might incur harm. This two-part review focuses on the attributes or concerns about specific vitamin consumption on CVD. The evidence for indiscriminate use of multivitamins indicates no consistent CVD benefit. Specific vitamins and/or combinations are suggested, but further supportive evidence is needed. Data presented in Part 1 indicated that folic acid and certain B-vitamins may decrease stroke, whereas niacin might raise mortality; beta-carotene mediates pro-oxidant effects, which may abate the benefits from other vitamins. In Part 2, data favor the anti-oxidant effects of vitamin C and the anti-atherogenic effects of vitamins C and E, but clinical evidence is inconsistent. Vitamin D may provide CV protection, but data are conflicting. Vitamin K appears neutral. Thus, there are favorable CV effects of individual vitamins (C/D), but randomized/controlled data are lacking. An important caveat regards the potential toxicity of increased doses of fat-soluble vitamins (A/D/E/K). As emphasized in Part 1, vitamins might benefit subjects who are antioxidant-deficient or exposed to high levels of oxidative-stress (e.g., diabetics, smokers, and elderly), stressing the importance of targeting certain subgroups for optimal results. Finally, by promoting CV-healthy balanced-diets, we could acquire essential vitamins and nutrients and use supplements only for specific indications.

Relationship of Daily Step Counts to All-Cause Mortality and Cardiovascular Events

BackgroundThe minimal and optimal daily step counts for health improvements remain unclear. ObjectivesA meta-analysis was performed to quantify dose-response associations of objectively measured step count metrics in the general population. MethodsElectronic databases were searched from inception to October 2022. Primary outcomes included all-cause mortality and incident cardiovascular disease (CVD). Study results were analyzed using generalized least squares and random-effects models. ResultsIn total, 111,309 individuals from 12 studies were included. Significant risk reductions were observed at 2,517 steps/d for all-cause mortality (adjusted HR [aHR]: 0.92; 95% CI: 0.84-0.999) and 2,735 steps/d for incident CVD (aHR: 0.89; 95% CI: 0.79-0.999) compared with 2,000 steps/d (reference). Additional steps resulted in nonlinear risk reductions of all-cause mortality and incident CVD with an optimal dose at 8,763 (aHR: 0.40; 95% CI: 0.38-0.43) and 7,126 steps/d (aHR: 0.49; 95% CI: 0.45-0.55), respectively. Increments from a low to an intermediate or a high cadence were independently associated with risk reductions of all-cause mortality. Sex did not influence the dose-response associations, but after stratification for assessment device and wear location, pronounced risk reductions were observed for hip-worn accelerometers compared with pedometers and wrist-worn accelerometers. ConclusionsAs few as about 2,600 and about 2,800 steps/d yield significant mortality and CVD benefits, with progressive risk reductions up to about 8,800 and about 7,200 steps/d, respectively. Additional mortality benefits were found at a moderate to high vs a low step cadence. These findings can extend contemporary physical activity prescriptions given the easy-to-understand concept of step count. (Dose-Response Relationship Between Daily Step Count and Health Outcomes: A Systematic Review and Meta-Analyses; CRD42021244747)

Omega-3 Polyunsaturated Fatty Acids Supplements and Cardiovascular Disease Outcome: A Systematic Review and Meta-Analysis on Randomized Controlled Trials.

Many meta-analyses and randomized controlled trials (RCTs) on the use of Omega-3 supplements for cardiovascular disease (CVD) have come to different outcomes. Besides, previous meta-analyses have missed some key RCTs on this topic. PubMed, EMBASE, Cochrane Library and Web of Science were manually searched for eligible RCTs on Omega-3 polyunsaturated fatty acids (PUFA) use for CVD. Risk estimates of each relevant outcome were calculated as a hazard ratio (HR) with 95% confidence interval (95% CI) using the random-effects model. Subgroup analysis was conducted according to the main characteristics of the population, sensitivity analysis would be performed if there was significant heterogeneity among analyses on relevant outcomes. Statistical heterogeneity was assessed using chi-square tests and quantified using I-square statistics. Nineteen eligible RCTs incorporating 116,498 populations were included. Omega-3 PUFA supplementation could not significantly improve the outcomes of major adverse cardiovascular events (MACE) (HR: 0.98, 95% CI: 0.91-1.06), myocardial infarction (MI) (HR: 0.86, 95% CI: 0.70-1.05), coronary heart disease (CHD) (HR: 0.90, 95% CI: 0.80-1.01), stroke (HR: 1.00, 95% CI: 0.91-1.10), SCD (sudden cardiac death) (HR: 0.90, 95% CI: 0.80-1.02), all-cause mortality (HR: 0.96, 95% CI: 0.89-1.04), hospitalization (HR: 0.99, 95% CI: 0.81-1.20), hospitalization for all heart disease (HR: 0.91, 95% CI: 0.83-1.00), hospitalization for heart failure (HR: 0.97, 95% CI: 0.91-1.04). Although omega-3 PUFA significantly reduced revascularization (HR: 0.90, 95% CI: 0.81-1.00) and cardiovascular mortality (CV mortality) (HR: 0.91, 95% CI: 0.85-0.97), risk for atrial fibrillation (AF) was also increased (HR: 1.56, 95% CI: 1.27-1.91). Subgroup analysis results kept consistent with the main results. Omega-3 PUFA supplementation could reduce the risk for CV mortality and revascularization, it also increased the AF incidence. No obvious benefits on other CVD outcomes were identified. Overall, potential CVD benefits and harm for AF should be balanced when using omega-3 PUFA for patients or populations at high risk.

ACTING EARLY TO PROTECT RENAL: BEYOND GLYCEMIC CONTROL OF SGLT2 INHIBITORS

Type 2 Diabetes Mellitus (T2DM) is the leading cause of chronic kidney disease (CKD), accounting for almost half of all cases of kidney failure that necessitate replacement therapy. Cardiovascular disease (CVD) is the leading cause of death in patients with T2DM and CKD. To lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule, sodium/glucose cotransporter 2 inhibitors (SGLT2-i) were developed. Consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death) were recognized in clinical trials designed to demonstrate the CVD safety of SGLT2i in type 2 diabetes mellitus (T2DM), as well as reductions in CVD events. The DECLARE-TIMI58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58, or DECLARE) trial in patients with T2DM, urinary albumin-creatinine ratio >300 mg/g, and estimated glomerular filtration rate of 30 to 90 mL/min/1.73 m2 established the kidney and CVD benefits of dapagliflozin in patients with CKD. SGLT2i boost glomerular hemodynamic function and are figured to augment other local and systemic processes that contribute to the development of CKD and CVD. According to latest Indonesian Society of Endocrinologist’s guideline, patients with T2DM was recommended to use SGLT2i to reduce their risk of CKD and CVD, in accordance with the clinical trial entry criteria. To achieve widespread use of these life-saving medications, effective implementation strategies are required.

Cardiovascular disease management in Australian adults with type 2 diabetes: insights from the CAPTURE study.

Type 2 diabetes (T2D) is a well-recognised cardiovascular disease (CVD) risk factor, and recent guidelines for the management of T2D include consideration of CVD risk. To assess whether contemporary clinical management of Australians with T2D is in accord with recent national and international guidelines. This Australia-specific analysis of the CAPTURE study, a non-interventional, cross-sectional study included adults diagnosed with T2D ≥180 days prior to providing informed consent and visiting primary or specialist care. Main outcome measures were the use of blood glucose-lowering medications (BGLMs), BGLMs with proven cardiovascular benefits and other CVD medications, stratified by CVD status and care setting. Of 824 Australian participants in the CAPTURE sample, 332 (40.3%) had CVD. Oral BGLMs were used by 83.9% of all participants, most commonly metformin (76.0%), dipeptidyl peptidase-4 inhibitors (28.8%), sodium-glucose cotransporter-2 inhibitors (SGLT2is; 21.8%) and sulfonylureas (21.7%). Insulin was used by 29.2% of participants. BGLMs with proven CV benefit were used by 22.6%; glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were less commonly used than SGLT2is in all CVD groups, but these drug classes were more often prescribed in specialist than primary care (SGLT2is 25.4 vs 20.7%, GLP-1 RAs 3.2 vs 0.8% respectively). Use of non-BGLMs for CVD risk reduction appeared consistent with guidelines. Use of BGLMs with CVD benefits appears low in Australia, irrespective of CVD status. This likely reflects the delay in translation of clinical evidence into contemporary care and prescribing restrictions.

Nitric Oxide-Releasing Platforms for Treating Cardiovascular Disease.

Cardiovascular disease (CVD) is the first leading cause of death globally. Nitric oxide (NO) is an important signaling molecule that mediates diverse processes in the cardiovascular system, thereby providing a fundamental basis for NO-based therapy of CVD. At present, numerous prodrugs have been developed to release NO in vivo. However, the clinical application of these prodrugs still faces many problems, including the low payloads, burst release, and non-controlled delivery. To address these, various biomaterial-based platforms have been developed as the carriers to deliver NO to the targeted tissues in a controlled and sustained manner. This review aims to summarize recent developments of various therapeutic platforms, engineered to release NO for the treatment of CVD. In addition, two potential strategies to improve the effectiveness of existing NO therapy are also discussed, including the combination of NO-releasing platforms and either hydrogen sulfide-based therapy or stem cell therapy. Hopefully, some NO-releasing platforms may provide important therapeutic benefits for CVD.

Estimated Life-Years Gained Free of New or Recurrent Major Cardiovascular Events With the Addition of Semaglutide to Standard of Care in People With Type 2 Diabetes and High Cardiovascular Risk.

Semaglutide, a glucagon-like peptide 1 receptor agonist, reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) at high risk of cardiovascular disease (CVD) in a post hoc analysis of pooled data from Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN) 6 and Peptide Innovation for Early Diabetes Treatment (PIONEER) 6. We estimated the benefit of adding semaglutide to standard of care (SoC) on life-years free of new/recurrent CVD events in people with T2D at high risk of CVD. The Diabetes Lifetime-perspective prediction (DIAL) competing risk-adjusted lifetime CVD risk model for people with T2D was developed previously. Baseline characteristics of the pooled cohort from SUSTAIN 6 and PIONEER 6 (POOLED cohort) (N = 6,480) were used to estimate individual life expectancy free of CVD for patients in the POOLED cohort. The hazard ratio of MACE from adding semaglutide to SoC was derived from the POOLED cohort (hazard ratio [HR] 0.76 [95% CI 0.62-0.92]) and combined with an individual's risk to estimate their CVD benefit. Adding semaglutide to SoC was associated with a wide distribution in life-years free of CVD gained, with a mean increase of 1.7 (95% CI 0.5-2.9) life-years. Estimated life-years free of CVD gained with semaglutide was dependent on baseline risk (life-years free of CVD gained in individuals with established CVD vs. those with cardiovascular risk factors only: 2.0 vs. 0.2) and age at treatment initiation. Adding semaglutide to SoC was associated with a gain in life-years free of CVD events that was dependent on baseline CVD risk and age at treatment initiation. This study helps contextualize the results of semaglutide clinical trials.

Meta-analysis of 17 clinical trials using omega-3 fatty acids in patients with cardiovascular disease

Background and Aims: Increased fish oil consumption has been associated with a lower risk of cardiovascular disease (CVD). Fish oils owe their CVD benefits to omega-3 fatty acids which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Multiple clinical trials, with the majority of them administering a combination of EPA and DHA, have been conducted in Western and Asian populations with mixed outcomes. This study aimed to determine whether omega-3 fatty acid formulations of EPA alone versus mixed combinations can confer protection in patients with CVD.

The role of SGLT2 inhibitors beyond glucose-lowering to cardio-renal protection

People with type 2 diabetes mellitus (T2DM) are at high risk of developing cardiovascular disease (CVD) and kidney disease. This enhanced cardio-renal risk persists despite improvements in care and treatments over the last 20 years. Intensive glucose control alone does not substantially reduce the risk of CVD and end stage kidney disease (ESKD). However, in 2015 the landmark EMPA-REG trial demonstrated for the first time the benefits of Empagliflozin a sodium-glucose co-transporter 2 (SGLT2) inhibitor on CVD events and mortality in people with T2DM. Since this trial several other SGLT2 Inhibitors including Dapagliflozin and Canagliflozin have demonstrated CVD benefits. SGLT2 inhibitors have also demonstrated significant reductions in the risk of hospitalization for heart failure (HHF) and ESKD. As a consequence of this growing evidence, there has been a shift in the focus of care in T2DM from glucose management to preservation of organ function. SGLT2 inhibitors have emerged as key treatment to reduce CVD, HHF and prevent progression of kidney disease. The benefits for reducing HHF and preventing ESKD have been observed in people with and without T2DM in large randomised controlled clinical trials. In T2DM the positive effects of SGLT2 inhibitors occur early and are independent of their glucose lowering effects. It is vital that all clinicians recognise the remarkable benefits of SGLT2 inhibitors and use this important class of drugs promptly and early to prevent CVD, HHF and ESKD.

Patient Selection for Intensive Blood Pressure Management Based on Benefit and Adverse Events

BackgroundIntensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients. ObjectivesThe aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment. MethodsThis was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment. ResultsAmong 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = −0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality. ConclusionsSPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062)

Prescribing in Type 2 Diabetes Patients With and Without Cardiovascular Disease History: A Descriptive Analysis in the UK CPRD

PurposeSome classes of glucose-lowering medications, including sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1-receptor agonists (GLP1-RAs) have cardio-protective benefit, but it is unclear whether this influences prescribing in the United Kingdom (UK). This study aims to describe class-level prescribing in adults with type 2 diabetes mellitus (T2DM) by cardiovascular disease (CVD) history using the Clinical Practice Research Datalink (CPRD). MethodsFour cross-sections of people with T2DM aged 18–90 and registered with their general practice for >1 year on 1st January 2017 (n = 166,012), 1st January 2018 (n = 155,290), 1st January 2019 (n = 152,602) and 31st December 2019 (n = 143,373) were identified. Age-standardised proportions for class use through time were calculated separately in those with and without CVD history and by total number of medications prescribed (one, two, three, four+). An analysis by UK country was also performed. FindingsAround 31% of patients had CVD history at each cross-section. Metformin was the most common treatment (>70% of those with and without CVD had prescriptions across all treatment lines). Overall use of SGLT2is and GLP1-RAs was low, with slightly less use in patients with CVD (SGLT2i: 9.8% and 13.8% in those with and without CVD respectively; GLP1-RA: 4.3% and 4.9%, December 2019). Use of SGLT2is as part of dual therapy was low but rose throughout the study. In January 2017, estimated use was 8.0% (95% CI 6.9–9.1%) and 8.9% (8.6–9.3%) in those with and without CVD. By December 2019 this reached 18.3% (17.0–19.5%) and 21.2% (20.6–21.7%) for those with and without CVD respectively. SGLT2i use as triple therapy increased: 22.7% (21.0–24.4%) and 25.9% (25.2–26.6%) in January 2017 to 41.3% (39.5–43.0%) and 45.5% (44.7–46.3%) in December 2019. GLP1-RA use also increased, but observed usage remained lower than SGLT2 inhibitors. Insulin use remained stable throughout, with higher use observed in those with CVD (16% vs 9.7% Dec 2019). Time trends in England, Wales, Scotland and Northern Ireland were similar, although class prevalence varied. ImplicationsAlthough use of SGLT2is and GLP1-RAs has increased, overall usage remains low with slightly lower use in those with CVD history, suggesting there is opportunity to optimise use of these medicines in T2DM patients to manage CVD risk. Insulin use was substantially more prevalent in those with CVD despite no evidence of CVD benefit. Further investigation of factors influencing this finding may highlight strategies to improve patient access to the most appropriate treatments, including those with evidence of cardiovascular benefit.

Adherence to antihypertensive medication and cardiovascular disease events in hypertensive patients: a dose-response meta-analysis of 2 769 700 participants in cohort study.

Recently, many studies have investigated the association between adherence to antihypertensive medication (AHM) and risk of cardiovascular disease (CVD) events for hypertensive patients; however, the results varied by different studies. The purpose of our meta-analysis was to explore the comprehensively summarized association between AHM adherence and risk of CVD events in hypertensive patients from cohort studies. A dose-response meta-analysis. We conducted a systematic search in two databases (PubMed and Embase) from 1974 to 15 December 2019 to identify English-language reports that assessed the association of AHM adherence with risk of CVD events in cohort studies. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by using a fixed- or random-effects model. Restricted cubic splines were used to evaluate the possible linear or non-linear association. We included 16 cohort studies with 2 769 700 participants in the present meta-analysis. The pooled RR of CVD events was 0.66 (95% CI, 0.56-0.78, I2 = 98.6%) for the highest versus lowest AHM adherence categories. We found a linear dose-response association of AHM adherence and CVD events (Pnonlinearity = 0.887), each 20% increase in AHM adherence was associated with a 13% reduced risk of CVD events (RR 0.87, 95% CI 0.83-0.92, I2 = 98.2%) in hypertensive patients. High AHM adherence has a protective effect on CVD events for hypertensive patients, and improving medication adherence may provide long-term CVD benefits.

SGLT2 Inhibition for CKD and Cardiovascular Disease in Type 2 Diabetes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation

Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to demonstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were observed. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio>300mg/g, and estimated glomerular filtration rate of 30 to<90mL/min/1.73m2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.

SGLT2 Inhibition for CKD and Cardiovascular Disease in Type 2 Diabetes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to demonstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were observed. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio >300 mg/g, and estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions in order to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.

LEADER Trial Eligibility and Preventable Cardiovascular Events in US Adults with Diabetes: the National Health and Nutrition Examination Surveys 2007-2016.

The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial showed the cardiovascular disease (CVD) benefits of liraglutide therapy among patients with type 2 diabetes mellitus (T2DM). We applied this trial to US adults with T2DM in terms of eligibility and preventable CVD events. We included US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Eligibility criteria from LEADER primary and secondary prevention cohorts were applied to determine potentially eligible US adults. We estimated the number of primary composite and secondary CVD endpoints that would occur based on LEADER treated and placebo published event rates, with the difference indicating the number of preventable events. Among 4672 (projected to 27.3 million [M]) adults we identified with T2DM, we estimated 800 (4.2 million) (15.4%) to fit LEADER eligibility criteria, including 205 (0.9 M) primary prevention 595 (3.3 M) secondary prevention subjects. Compared to LEADER trial participants, our sample had higher proportions of women and minorities, prior angina, chronic kidney disease, and lipid-lowering medication use. We estimated 21,209 primary composite CVD events, 29,691 extended CVD composite outcomes, 16,967 all-cause deaths, 16,967 cardiovascular deaths, 12,725 myocardial infarctions, and 12,725 microvascular events would be prevented annually if our eligible T2DM subjects were on liraglutide. Liraglutide may prevent many fatal and non-fatal CVD events if provided to US adults meeting LEADER eligibility criteria. More efforts are needed to educate the healthcare providers on the CVD benefits from newer diabetes therapies, including liraglutide.

Physical activity and risk of cardiovascular disease by weight status among U.S adults.

PurposeWe sought to determine whether the association between physical activity and 10-year cardiovascular disease (CVD) risk varies among normal weight, overweight, and obese adults in a nationally-representative sample of the United States.MethodsData were from the National Health and Nutrition Examination Survey 2007–2016. A subset of 22,476 participants aged 30–64 years was included with no CVD history. Physical activity level was self-reported and stratified into sedentary (0 min/week), inactive (1–149 mins/week), or active (≥150 mins/week) of moderate or vigorous activities. Framingham risk scores were classified as low/intermediate (<20%) or high 10-year CVD risk (≥20%).ResultsThe average age of the population was 45.9 years, 52.3% were female, 33.6% were overweight (BMI 25.0–29.9kg/m2), and 35.7% were obese (BMI≥30kg/m2). Individuals who were overweight and obese had a higher 10-year CVD risk compared to those with normal weight (9.5 vs. 10.1 vs. 6.3%, P<0.001). The association of physical activity and high 10-year CVD risk differed by weight status. Among overweight and obese adults, individuals engaged in any physical activity had lower odds ofhigh 10-year CVD risk compared to sedentary individuals (overweight: OR active = 0.48, 95% CI: 0.36–0.64; OR inactive = 0.53, 95% CI: 0.45–0.86; obese: OR active = 0.50, 95% CI: 0.37–0.68; OR inactive = 0.66, 95% CI: 0.49–0.89). Among normal weight adults, individuals who were physically active had lower odds of high 10-year CVD risk (OR = 0.59, 95% CI: 0.28–0.87). When compared the joint effects of physical activity level and weight status, physical activity was associated with a larger magnitude of reduced odds of 10-year CVD risk than weight status.ConclusionParticipation in any level of physical activity is associated with a lower 10-year CVD risk for overweight and obese adults. Future studies are needed to identify effective modes and doses of exercise that offer optimal CVD benefits for populations with different weight statuses.

Abstract P482: Long-term Health and Cost Impact of the 2017 American College of Cardiology/American Heart Association (2017 Acc/aha) Hypertension Guidelines for Low-risk Adults

Introduction: The 2017 ACC/AHA guidelines redefined stage 1 hypertension to include blood pressure 130-139 mmHg/80-89 mmHg and recommended non-pharmacologic interventions (e.g., DASH diet, physical activity) for those with stage 1 hypertension and a low 10-year risk of cardiovascular disease (CVD). The cost-effectiveness of achieving target blood pressure in this low risk population in the clinical setting (via identification, diagnosis, and counseling on diet and exercise) has not been assessed. Methods: We used the Cardiovascular Disease Policy Model (CVDPM), a dynamic state-transition model of CVD in US adults to simulate achieving blood pressure control in low-risk adults aged 35-64 years with untreated stage 1 hypertension based on the 2017 ACC/AHA guidelines. Outcomes included incident CVD (coronary heart disease and stroke), CVD healthcare costs (2018 dollars), and quality-adjusted life years (QALYs) over 10 years. We projected outcomes assuming all low-risk young adults achieve control. We then varied the degree to which patients would change behaviors following diagnosis, using low uptake (20%) and high uptake (70%) estimates sourced from literature. We tested the sensitivity of health gains to decrements in QALYs associated with receiving a diagnosis using estimates from the Global Burden of Disease. Results: An estimated 7.0 million men and 6.6 million women age 35-64 years would be newly diagnosed with stage 1 hypertension and indicated for non-pharmacologic interventions according to 2017 ACC/AHA. Achieving targets of &lt;130/80 mmHg is projected to prevent 63,200 incident CVD events and 4,800 CVD deaths and lower CVD related healthcare costs by $3.6 billion (2018 USD) over 10 years compared to no BP change. Assuming less than complete control (because of variable uptake of non-pharmacologic interventions) resulted in lower rates of CVD prevention (low uptake - 13,900 events prevented and $0.8 billion lower costs; high uptake 41,000 events prevented and $2.3 billion lower costs). In all scenarios, the magnitude of QALYs gained from preventing CVD was highly sensitive to decrements associated with anxiety from receiving a diagnosis. Conclusions: Achieving 2017 ACC/AHA stage 1 hypertension goals in newly diagnosed low-risk adults would result in substantial CVD benefit and reductions in CVD-related healthcare costs. . If these goals are to be achieved in the clinical setting, gains are likely to be offset by degree of uptake of counseling regarding non-pharmacologic interventions and anxiety related to a new diagnosis of hypertension.