Cardiometabolic Therapy Research Articles

The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

We aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association. Participants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined. A total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association. High BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

Anti-ischemic and cardiometabolic therapy in cardiovascular pathology

The purpose of this study was to study the effect of Kardioton therapy on myocardial ischemia in patients with arterial hypertension. The drug Kardioton is a natural cardioprotector; strengthens the heart muscle by improving its oxygen supply, stops inflammatory processes in the myocardium; has anti-ischemic, cardiometabolic, hypotensive effect. It is recommended for disorders of the cardiovascular system, with increased physical activity. Based on the conducted research, it can be concluded that Kardioton is well tolerated by patients and is an effective treatment: cardiometabolic and anti-ischemic effects due to normalization of cardiomyocyte metabolism have been obtained.

Impact of a Cardiometabolic Clinic in Addressing Residual Cardiovascular Risk

BackgroundDespite the significant impact of statin therapy, patients continue to face substantial residual cardiovascular risk. These risks are particularly prominent in patients with both type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). We examine the effectiveness of a cardiometabolic clinic, embedded within a suburban cardiology private practice, in identifying and managing several of these multifaceted risks. MethodsWe collated interventions for the first 100 patients with T2D and ASCVD who attended a minimum of two appointments at the clinic. ResultsFollowing an average of 2.4 clinic visits, 44 of 100 patients had undergone intensification of lipid-lowering therapy, with 16 initiated on PCSK9-directed therapies. This resulted in 85 of 100 patients achieving LDL-C levels below the 2022 ACC Expert Consensus Decision Pathway recommendations for intensification. Lipoprotein(a) was measured in 80 patients, revealing elevated levels in 22. At baseline, 18 and 32 patients were on glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), respectively. This increased to 80 and 66 patients on GLP1RA and SGLT2i, respectively, with 94 patients on either class and 52 patients on both. Figure 1 presents baseline and follow-up use of cardiometabolic therapies. ConclusionThe cardiometabolic clinic effectively identified and intensified management of several residual cardiovascular risks in patients with T2D and ASCVD. Extensive use of combination lipid-lowering therapies substantially addressed cholesterol-related risk, and initial experiences support the feasibility of high-volume implementation of GLP1RA and SGLT2i therapies in this population.

The effectiveness of modern immunomodulatory and cardiometabolic therapy in correction the risk of hospital complications in patients with acute myocardial infarction with myocardial revascularization: the results of multifactorial analysis

The effectiveness of modern immunomodulatory and cardiometabolic therapy in correction the risk of hospital complications in patients with acute myocardial infarction with myocardial revascularization: the results of multifactorial analysis

Abstract 12678: Marketplace Plan Designs for Cardiometabolic Therapies in Rural and Urban Counties in the US

Introduction: In the US, important variation exists in cardiovascular risk factor burden and rates of death across rural and urban counties. Affordability and non-financial mechanisms can present as barriers to treatment, yet little is known about if there may be systematic variation in plan design by rural and urban settings. We assessed whether rural or urban county type is associated with insurance plan design for sacubitril/valsartan, dapagliflozin, and empagliflozin. Methods: We evaluated the median premium silver-level plan from 26 selected states with federally-facilitated marketplaces based on the Bureau of Economic Analysis Regions. We then examined features such as coverage, tier, copay or coinsurance, expected out-of-pocket costs for 30 day supply, and coverage contingent non-financial elements including prior authorization, step therapy, and quantity limits. Logistic regression models, stratified by medication and state, assessed if rural/urban county type was a predictor of cost-sharing mechanism, coverage contingent elements, or out-of-pocket costs. Results: The mean population of urban and rural counties was 1.2M (±1.3M) and 19,364 (± 40,006), respectively. Urban counties had a higher proportion of Black/Hispanic individuals (31% vs. 16%) and higher median household incomes ($65,835 ± $17,452 vs. $47,212 ± $10,549); all P < 0.01. Over 90% of plans covered each of the three medications, irrespective of rural/urban county type. Across each of the three medications and states, plans in urban counties had higher odds of including prior authorization (OR: 10.59; 95% CI: 2.55-43.96; P = 0.001) and use of coinsurance (OR: 9.06; 95% CI: 2.55-32.20; P = 0.001) compared with plans in rural counties. For each drug, predicted out-of-pocket costs differed as much as $250 between rural and urban counties for a given state. Conclusion: Most plans cover these newer cardiometabolic therapies across sampled US counties, but there was substantial variation in plan architecture across counties with greater utilization of prior authorization and coinsurance as a cost-sharing mechanism in urban counties. Given a greater population density, these mechanisms may guard against moral hazard and overutilization in urban settings.

Cardiometabolic Therapy and Mortality in Very Old Patients With Diabetes Hospitalized due to COVID-19.

BackgroundThe effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, especially very old patients, are not well-known. This work aims to analyze the association between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, and lipid-lowering drugs) and in-hospital mortality among patients ≥80 years with type 2 diabetes mellitus hospitalized for COVID-19.MethodsWe conducted a nationwide, multicenter, observational study in patients ≥80 years with type 2 diabetes mellitus hospitalized for COVID-19 between March 1 and May 29, 2020. The primary outcome measure was in-hospital mortality. A multivariate logistic regression analysis were performed to assess the association between preadmission cardiometabolic therapy and in-hospital mortality.ResultsOf the 2,763 patients ≥80 years old hospitalized due to COVID-19, 790 (28.6%) had T2DM. Of these patients, 385 (48.7%) died during admission. On the multivariate analysis, the use of dipeptidyl peptidase-4 inhibitors (AOR 0.502, 95%CI 0.309-0.815, p=0.005) and angiotensin receptor blockers (AOR 0.454, 95%CI 0.274-0.759, p=0.003) were independent protectors against in-hospital mortality whereas the use of acetylsalicylic acid was associated with higher in-hospital mortality (AOR 1.761, 95%CI 1.092-2.842, p=0.020). Other antidiabetic drugs, angiotensin-converting enzyme inhibitors and statins showed neutral association with in-hospital mortality.ConclusionsWe found important differences between cardiometabolic drugs and in-hospital mortality in older patients with type 2 diabetes mellitus hospitalized for COVID-19. Preadmission treatment with dipeptidyl peptidase-4 inhibitors and angiotensin receptor blockers could reduce in-hospital mortality; other antidiabetic drugs, angiotensin-converting enzyme inhibitors and statins seem to have a neutral effect; and acetylsalicylic acid could be associated with excess mortality.

Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia.

Cardiovascular disease (CVD) is the leading cause of death worldwide and is the clinical manifestation of the atherosclerosis. Elevated LDL-cholesterol levels are the first line of therapy but the increasing prevalence in type 2 diabetes mellitus (T2DM) has positioned the cardiometabolic risk as the most relevant parameter for treatment. Therefore, the control of this risk, characterized by dyslipidemia, hypertension, obesity, and insulin resistance, has become a major goal in many experimental and clinical studies in the context of CVD. In the present review, we summarized experimental studies and clinical trials of recent anti-diabetic and lipid-lowering therapies targeted to reduce CVD. Specifically, incretin-based therapies, sodium-glucose co-transporter 2 inhibitors, and proprotein convertase subtilisin kexin 9 inactivating therapies are described. Moreover, the novel molecular mechanisms explaining the CVD protection of the drugs reviewed here indicate major effects on vascular cells, inflammatory cells, and cardiomyocytes, beyond their expected anti-diabetic and lipid-lowering control. The revealed key mechanism is a prevention of acute cardiovascular events by restraining atherosclerosis at early stages, with decreased leukocyte adhesion, recruitment, and foam cell formation, and increased plaque stability and diminished necrotic core in advanced plaques. These emergent cardiometabolic therapies have a promising future to reduce CVD burden.

Effectiveness of Cardiometabolic Therapy in the Treatment of Acute Coronary Syndrome without ST-segment Elevation in Perimenopausal Women

Acute forms of coronary heart disease (CHD) are one of the most pressing problems in the structure of morbidity and mortality, especially among perimenopausal women. Of particular interest are approaches to the medical correction of acute myocardial ischemia that occurs on the background of non-obstructive lesions or intact coronary arteries. The objective: to study the effectiveness of a fixed combination of meldonium with γ-butyrobetaine (γ-BB) as part of the optimal pharmacotherapy of GKSbelST. Materials and methods. 81 women with percutaneous and postmenopausal GKSbelST at the age of 39–69 years (mean age – 50.26 ± 1.24 years) were examined. Patients were evaluated major circadian blood pressure monitoring parameters (MMAD) was determined levels of female sex hormones (estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH)), circulating endothelial dysfunction markers (endothelial NO-synthase (eNOS), endothelin-1 (ET-1)), indicators of systemic inflammation (PSA) and POL (malonic dialdehyde (MDA), ceruloplasmin (CP)), the main indicators of lipid, carbohydrate and purine metabolism at the beginning of the study on the first day of hospitalization and after 2 weeks hospital treatment. Patients were divided into two groups. The 1-st group (n = 29) included women (average age – 51.26 ± 1.82 years), to whom a fixed combination of γ-BB dihydrate (60 mg) and meldonium dihydrate (180 mg) was added to the standard OMT (Kapikor, “Olainfarm”, Latvia) 2 capsules 2 times a day; in the 2nd group (n = 52) – women with GKSbelST women (average age – 49.64 ± 1.12 years), who received only the standard OMT complex. Results. On the first day of hospitalization of patients with GKSbelST, there was a decrease in eNOS and an increase in ET-1, MDA, CB, and SRP compared to practically healthy individuals, with ABPM, an increase in BP variability (VAD), an increase in BP (HV AD), time index (YV ) at night and insufficient nightly decrease in blood pressure. Compared with women of the 2 nd group, two-week treatment of patients of the 1st group significantly accelerates the restoration of endothelial function. The content of eNOS increased in the 1st group by 22.13% (from 191.76 ± 7.67 to 234.82 ± 17.26 pg / ml; p 0.05), levels of E T-1 decreased (by 23.45% in the 1st group (from 15 , 31 ± 0.60 to 11.71 ± 0.68 pg / ml; p 0.05). Conclusion. Adding to the GKSbelST treatment in women of a fixed combination of meldonium with γ-BB significantly speeds up the restoration of endothelial function and contributes to a decrease in peripheral resistance, balances vascular tone, stabilizes systemic and regional blood flow, which is manifested by the rapid positive dynamics of pressure loads, improved clinical course of NS and reduced hospitalization. Women who took the meldonium with γ-BB combination, in addition to the standard OMT, recorded significant positive changes in the content of female sex hormones in the blood, in particular estradiol (by 20.8%), which may be a consequence of the beneficial effect of meldonium with γ-BB on the microcirculation ovary.

Dynamic pattern in the structural-functional parameters of the heart in children with myocardial pathology, taking into account morphological functional features of the right ventricle

The purpose of the study was to study the dynamics of changes in morphofunctional heart changes inchildren with non-inflammatory pathology of myocardium on the background of ongoing therapy. There were examined 115 patients (11–18 years old) with various heart diseases.The systolic dysfunction of the myocardium was diagnosedin 50 of them, and treatment was prescribed. In the dynamics, a year later, 40 patients were examined. It has been established that in children and adolescents, along withpathogenetic and cardiometabolic therapy, in parallel with the improvement of the structure and function of the right ventricle of the heart, morphofunctional indicators ofthe left ventricle are improved.

Dynamic pattern in the structural-functional parameters of the heart in children with myocardial pathology, taking into account morphological functional features of the right ventricle

The purpose of the study was to study the dynamics of changes in morphofunctional heart changes inchildren with non-inflammatory pathology of myocardium on the background of ongoing therapy. There were examined 115 patients (11–18 years old) with various heart diseases.The systolic dysfunction of the myocardium was diagnosedin 50 of them, and treatment was prescribed. In the dynamics, a year later, 40 patients were examined. It has been established that in children and adolescents, along withpathogenetic and cardiometabolic therapy, in parallel with the improvement of the structure and function of the right ventricle of the heart, morphofunctional indicators ofthe left ventricle are improved.

Abstract 21161: Use of an Open Access Multi-Sponsor Data Sharing Platform in Cardiology

Background: Sharing of patient-level clinical trial data has been widely endorsed, yet little is known how extensively these have been utilized in cardiology. Methods: We extracted data from ClinicalStudyDataRequest.com (CSDR), a large, multi-sponsor, open access platform hosting patient-level data from completed studies sponsored by 13 pharmaceutical companies. Results: From January 2013 to May 2017, the platform had data from 3,374 clinical trials of which 537 (16%) were specific to cardiometabolic therapeutics (phase 1 36%; phase 2 17%; phase 2/3 1%; phase 3 42%; phase 4 4%). These covered 74 therapies and 398,925 patients ( Figure 1 ). Diabetes mellitus (60%) and hypertension (15%) were the most common study topics ( Figure 2 ). Median time from study completion to data availability was 79 months. As of March 2017, CSDR had received 305 submitted proposals, of which 154 had signed data sharing agreements. Thirty of these proposals were related to cardiometabolic therapies and requested data from 81 unique studies (90% of which were phase 3/4). Most proposals were from the US (53%) and half did not report a funding source. Most proposals focused on post hoc exploratory analyses, research methodology, or meta-analyses; only 2 re-analyzed the original study primary hypothesis. To date, 3 peer-reviewed papers have been published (median 19 months from the data sharing agreement). Conclusions: Although data from over 500 cardiometabolic trials have been made available on a large, multi-sponsor open access platform, only 15% of these trials have been accessed by investigators thus far and few findings have reached publication.

Availability and Use of Shared Data From Cardiometabolic Clinical Trials.

Sharing of patient-level clinical trial data has been widely endorsed. Little is known about how extensively these data have been used for cardiometabolic diseases. We sought to evaluate the availability and use of shared data from cardiometabolic clinical trials. We extracted data from ClinicalStudyDataRequest.com, a large, multisponsor data-sharing platform hosting individual patient-level data from completed studies sponsored by 13 pharmaceutical companies. From January 2013 to May 2017, the platform had data from 3374 clinical trials, of which 537 (16%) evaluated cardiometabolic therapeutics (phase 1, 36%; phase 2, 17%; phase 2/3, 1%; phase 3, 42%; phase 4, 4%). They covered 74 therapies and 398 925 patients. Diabetes mellitus (60%) and hypertension (15%) were the most common study topics. Median time from study completion to data availability was 79 months. As of May 2017, ClinicalStudyDataRequest.com had received 318 submitted proposals, of which 163 had signed data-sharing agreements. Thirty of these proposals were related to cardiometabolic therapies and requested data from 79 unique studies (15% of all trials, 29% of phase 3/4 trials). Most (96%) data requesters of cardiometabolic clinical trial data were from academic centers in North America and Western Europe, and half the proposals were unfunded. Most proposals were for secondary hypothesis-generating questions, with only 1 proposed reanalysis of the original study primary hypothesis. To date, 3 peer-reviewed articles have been published after a median of 19 months (9-32 months) from the data-sharing agreement. Despite availability of data from >500 cardiometabolic trials in a multisponsor data-sharing platform, only 15% of these trials and 29% of phase 3/4 trials have been accessed by investigators thus far, and a negligible minority of analyses have reached publication.

Depressive symptoms and adherence to cardiometabolic therapies across phases of treatment among adults with diabetes: the Diabetes Study of Northern California (DISTANCE).

ObjectiveAmong adults with diabetes, depression is associated with poorer adherence to cardiometabolic medications in ongoing users; however, it is unknown whether this extends to early adherence among patients newly prescribed these medications. This study examined whether depressive symptoms among adults with diabetes newly prescribed cardiometabolic medications are associated with early and long-term nonadherence.Patients and methodsAn observational follow-up of 4,018 adults with type 2 diabetes who completed a survey in 2006 and were newly prescribed oral antihyperglycemic, antihypertensive, or lipid-lowering agents within the following year at Kaiser Permanente Northern California was conducted. Depressive symptoms were examined based on Patient Health Questionnaire-8 scores. Pharmacy utilization data were used to identify nonadherence by using validated methods: early nonadherence (medication never dispensed or dispensed once and never refilled) and long-term nonadherence (new prescription medication gap [NPMG]: percentage of time without medication supply). These analyses were conducted in 2016.ResultsPatients with moderate-to-severe depressive symptoms had poorer adherence than nondepressed patients (8.3% more patients with early nonadherence, P=0.01; 4.9% patients with longer NPMG, P=0.002; 7.8% more patients with overall nonadherence [medication gap >20%], P=0.03). After adjustment for confounders, the models remained statistically significant for new NPMG (3.7% difference, P=0.02). There was a graded association between greater depression severity and nonadherence for all the models (test of trend, P<0.05).ConclusionDepressive symptoms were associated with modest differences in early and long-term adherence to newly prescribed cardiometabolic medications in diabetes patients. Interventions targeting adherence among adults with diabetes and depression need to address both initiation and maintenance of medication use.

Cardio-metabolic therapy of cardiovascular diseases, the role of potassium and magnesium

The relevance of cardiovascular disease for people of our country cannot be overemphasized. The convincing proof of this is its leading place in the structure of total mortality of Ukrainians. Metabolic cardioprotective therapy contributes to survival effect in ischemia (hypoxia) through direct effects on cardiomyocytes. Today metabolic therapy received evidence base and rightfully occupies an important place in treatment of cardiovascular disease, entering the international recommendations. The current data about features of cardio-metabolic therapy with emphasis on the role of magnesium and potassium are presented in the article. Application of cardio-metabolic drugs in combination with drugs of hemodynamic actions provide additional opportunities for the treatment of patients with cardiovascular diseases, especially in polimorbidity, allows strengthen anti-ischemic effect in target organs, thus ensuring a better quality of life.

An algorithm to identify medication nonpersistence using electronic pharmacy databases.

Identifying patients who are medication nonpersistent (fail to refill in a timely manner) is important for healthcare operations and research. However, consistent methods to detect nonpersistence using electronic pharmacy records are presently lacking. We developed and validated a nonpersistence algorithm for chronically used medications. Refill patterns of adult diabetes patients (n = 14,349) prescribed cardiometabolic therapies were studied. We evaluated various grace periods (30-300 days) to identify medication nonpersistence, which is defined as a gap between refills that exceeds a threshold equal to the last days' supply dispensed plus a grace period plus days of stockpiled medication. Since data on medication stockpiles are typically unavailable for ongoing users, we compared nonpersistence to rates calculated using algorithms that ignored stockpiles. When using grace periods equal to or greater than the number of days' supply dispensed (i.e., at least 100 days), this novel algorithm for medication nonpersistence gave consistent results whether or not it accounted for days of stockpiled medication. The agreement (Kappa coefficients) between nonpersistence rates using algorithms with versus without stockpiling improved with longer grace periods and ranged from 0.63 (for 30 days) to 0.98 (for a 300-day grace period). Our method has utility for health care operations and research in prevalent (ongoing) and new user cohorts. The algorithm detects a subset of patients with inadequate medication-taking behavior not identified as primary nonadherent or secondary nonadherent. Healthcare systems can most comprehensively identify patients with short- or long-term medication underutilization by identifying primary nonadherence, secondary nonadherence, and nonpersistence.

Cytokine production from peripheral blood mononuclear cells and polymorphonuclear leukocytes in patients studied for suspected obstructive sleep apnea

The relationship between obstructive sleep apnea (OSA) and atherosclerosis-related inflammation has been poorly investigated, particularly focusing on functional responses of immune cells playing a key role in atherogenesis and in comparison with control groups with similar cardiovascular risk factors which are known to be themselves associated with inflammation. We sought to determine cellular tumor necrosis factor-alpha (TNF-α) production from peripheral blood mononuclear cells (PBMCs) and interleukin (IL)-8 release from neutrophils (PMNs) in patients studied for suspected OSA. Thirty-six consecutive patients who underwent a nocturnal complete cardiorespiratory evaluation for suspected OSA were initially evaluated. Serum, PBMCs, and PMNs were isolated (at baseline and after 12 weeks) from patients with apnea-ipopnea index (AHI) >20 (OSA group, n = 16) and from control patients with AHI <5 (nonOSA group, n = 11). All patients continued the same pharmacological therapy for 12 weeks; the OSA group was additionally treated with nocturnal continuous positive-airway-pressure ventilation (cPAP). The two groups had similar clinical characteristics (prevalence of hypertension, dyslipidemia, diabetes, and cardio-metabolic therapies) except for obesity. Resting and stimulated TNF-α production from PBMCs and IL-8 release from PMNs were similar in the two groups. Serum cytokines resulted within the normal range. In the OSA group, cPAP was not associated with changes in cellular responses. In patients showing similar prevalence of major cardiovascular risk factors and cardio-metabolic therapies, differing for the presence or absence of OSA, cytokine productions from PBMC and PMN were similar and were not modified during cPAP therapy. Studies designed to investigate OSA-associated inflammation should carefully match the control group subjects.