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New approaches for the management of patients with multiple cardiometabolic risk factors.

Therapeutic strategies currently available for the management of cardiometabolic risk factors focus mainly on individual factors, and do not target the underlying cause of cardiovascular and metabolic diseases. The Rimonabant-in-Obesity (RIO) programme consists of four 1-2 yr Phase III trials, RIO-Europe, RIO-Lipids, RIO-North America (NA), and RIO-Diabetes, designed to assess the efficacy and safety of rimonabant in the treatment of multiple cardiometabolic risk factors in 6600 overweight/obesity patients. After 1 yr, results from the RIO-NA anci RIO-Europe trials, showed that treatment with rimonabant 20mg/day improved HDL-C (p< 0.001), triglycerides (p< 0.001), fasting insulin (p< 0.001) and insulin resistance (p=0.002 and p< 0.001 for RIO-Europe and RIO-NA, respectively) compared to placebo. The results of both studies also showed significant and sustained mean reductions in waist circumference (p< 0.001), and weight (p< 0.001) for rimonabant 20 mg/day compared with placebo. Similar improvements were seen in the RIO-Lipids trial at 1 yr and these results were consistently maintained over 2 yr in RIO-NA. The RIO-Europe and RIO-NA trials showed that improvements in HDL-C and TG levels with rimonabant over 1 yr, compared with bodyweight, were beyond that attributable to weight loss alone [40 and 55% for HDL-C and triglyceride (TG), respectively for RIO-Europe and 58 and 47%, respectively for RIO-NA]. Additionally, in RIO-NA, changes in fasting insulin and homeostasis model assessment insulin resistance (HOMA-IR), were beyond weight loss alone (50 and 51%, respectively). Rimonabant was well tolerated and the majority of adverse events reported were mild and transient, and occurred early in the treatment period. Rimonabant, the first cannabinoid receptor type 1 (CB1) receptor blocker, reduces weight and waist circumference, and improves lipid and glucose metabolism.

Cannabinoid Receptor Modulators↗

Effects of Moderate-Frequency Resistance Training on Cardiometabolic Risk Factors in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Resistance training (RT) effectively manages cardiometabolic risk factors in adults, but the specific effects of moderate-frequency RT (2-3 sessions/week) in adults with overweight or obesity are understudied. OBJECTIVE: This study aimed to evaluate moderate-frequency RT's effects on cardiometabolic risk factors in this population and quantify effect sizes. DATA SOURCES: PubMed, Web of Science, EMBASE, and Cochrane Library searched up to July 2025. ELIGIBILITY: English randomized controlled trials (RCTs) comparing RT (&#x2265;&#x2009;7&#x2009;weeks) to nonexercise control; nonathletic adults &#x2265;&#x2009;18&#x2009;years with BMI&#x2009;&#x2265;&#x2009;25&#x2009;kg/m2. PARTICIPANTS: 454 participants across 12 RCTs (mean age 58.93&#x2009;&#xb1;&#x2009;12.87&#x2009;years; mean BMI 31.2&#x2009;&#xb1;&#x2009;3.5&#x2009;kg/m2; ~50% female). RESULTS: RT significantly reduced diastolic blood pressure (MD&#x2009;=&#x2009;-1.53&#x2009;mmHg; 95% CI: -2.16 to -0.91; p&#x2009;<&#x2009;0.01), LDL-C (MD&#x2009;=&#x2009;-0.25&#x2009;mmol/L; 95% CI: -0.41 to -0.08; p&#x2009;<&#x2009;0.01), and triglycerides (MD&#x2009;=&#x2009;-0.17&#x2009;mmol/L; 95% CI: -0.30 to -0.04; p&#x2009;=&#x2009;0.01). No significant effects on systolic blood pressure, mean arterial pressure, waist circumference, glycemic markers, total cholesterol, or HDL-C. Subgroup analyses showed larger LDL-C/triglyceride improvements with concurrent dietary control. CONCLUSION: Moderate-frequency RT inconsistently improves cardiometabolic risk factors, benefiting diastolic blood pressure, LDL-C, and triglycerides but not glycemic or other parameters. Combining with dietary control may enhance benefits, supporting RT as a complementary strategy in multimodal lifestyle interventions. TRIAL REGISTRATION PROSPERO: CRD42022343167.

Humans↗

Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial.

CONTEXT: Rimonabant, a selective cannabinoid-1 receptor blocker, may reduce body weight and improve cardiometabolic risk factors in patients who are overweight or obese. OBJECTIVE: To compare the efficacy and safety of rimonabant with placebo each in conjunction with diet and exercise for sustained changes in weight and cardiometabolic risk factors over 2 years. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of 3045 obese (body mass index > or =30) or overweight (body mass index >27 and treated or untreated hypertension or dyslipidemia) adult patients at 64 US and 8 Canadian clinical research centers from August 2001 to April 2004. INTERVENTION: After a 4-week single-blind placebo plus diet (600 kcal/d deficit) run-in period, patients were randomized to receive placebo, 5 mg/d of rimonabant, or 20 mg/d of rimonabant for 1 year. Rimonabant-treated patients were rerandomized to receive placebo or continued to receive the same rimonabant dose while the placebo group continued to receive placebo during year 2. MAIN OUTCOME MEASURES: Body weight change over year 1 and prevention of weight regain during year 2. Additional efficacy measures included changes in waist circumference, plasma lipid levels, and other cardiometabolic risk factors. RESULTS: At year 1, the completion rate was 309 (51%) patients in the placebo group, 620 (51%) patients in the 5 mg of rimonabant group, and 673 (55%) patients in the 20 mg of rimonabant group. Compared with the placebo group, the 20 mg of rimonabant group produced greater mean (SEM) reductions in weight (-6.3 [0.2] kg vs -1.6 [0.2] kg; P<.001), waist circumference (-6.1 [0.2] cm vs -2.5 [0.3] cm; P<.001), and level of triglycerides (percentage change, -5.3 [1.2] vs 7.9 [2.0]; P<.001) and a greater increase in level of high-density lipoprotein cholesterol (percentage change, 12.6 [0.5] vs 5.4 [0.7]; P<.001). Patients who were switched from the 20 mg of rimonabant group to the placebo group during year 2 experienced weight regain while those who continued to receive 20 mg of rimonabant maintained their weight loss and favorable changes in cardiometabolic risk factors. Use of different imputation methods to account for the high rate of dropouts in all 3 groups yielded similar results. Rimonabant was generally well tolerated; the most common drug-related adverse event was nausea (11.2% for the 20 mg of rimonabant group vs 5.8% for the placebo group). CONCLUSIONS: In this multicenter trial, treatment with 20 mg/d of rimonabant plus diet for 2 years promoted modest but sustained reductions in weight and waist circumference and favorable changes in cardiometabolic risk factors. However, the trial was limited by a high drop-out rate and longer-term effects of the drug require further study. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00029861.

Adult↗

Rimonabant: a cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors.

Rimonabant is a first selective blocker of the cannabinoid receptor type 1 (CB1) being developed for the treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking. In four large trials, after one year of treatment, rimonabant 20 mg led to greater weight loss and reduction in waist circumference compared with placebo. Therapy with rimonabant is also associated with favorable changes in serum lipid levels and an improvement in glycemic control in prediabetes patients and in type 2 diabetic patients. At the same dose, rimonabant significantly increased cigarette smoking quit rates as compared with placebo. Rimonabant seems to be well tolerated, with a primary side effect of mild nausea. As an agent with a novel mechanism of action, rimonabant has a potential to be a useful adjunct to lifestyle and behavior modification in treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking.

Animals↗

New and emerging strategies for reducing cardiometabolic risk factors.

Several new drug therapies with beneficial effects on more than one of the cardiometabolic risk factors that contribute to the metabolic syndrome have been developed recently or are under investigation. Emerging risk factors for coronary heart disease (CHD), including low concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 (apoA-1), high levels of high-sensitivity C-reactive protein, and small dense low-density lipoprotein cholesterol particles, have been identified. We provide a detailed description of the mechanisms of action and findings from clinical trials of the new drug therapies and discuss established drug therapies with beneficial effects on emerging risk factors for CHD. The new and emerging drug therapies include an antiobesity agent that reduces atherogenic dyslipidemia and abnormal glucose metabolism; cholesteryl ester transfer protein inhibitors that increase HDL cholesterol and apoA-1 levels; glitazars that increase HDL cholesterol and decrease triglyceride concentrations, as well as improve abnormal glucose metabolism; and the amylin analog pramlintide and the incretin mimetic exenatide, both of which reduce body weight as well as improve abnormal glucose metabolism. The insulin-sensitizing effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs), which may help prevent new-onset diabetes mellitus, and the beneficial effects of the ARB telmisartan on the glucose and lipid profiles also are presented.

Anti-Obesity Agents↗

Is the number of documented diabetes process-of-care indicators associated with cardiometabolic risk factor levels, patient satisfaction, or self-rated quality of diabetes care? The Translating Research into Action for Diabetes (TRIAD) study.

OBJECTIVE: Simple process-of-care indicators are commonly recommended to assess and compare quality of diabetes care across health plans. We sought to determine whether variation in the number of simple diabetes processes of care across provider groups is associated with variation in other quality indicators, including cardiometabolic risk factor levels, patient satisfaction with care, or patient-rated quality of care. RESEARCH DESIGN AND METHODS: We used cross-sectional survey and chart audit data for 8,733 patients with diabetes who received care from 68 provider groups nested in 10 health plans that participated in the Translating Research Into Action for Diabetes study. Analyses using hierarchical regression models assessed associations of the mean number of seven simple process measures with each of the following: HbA(1c) (A1C), systolic blood pressure (SBP), HDL and LDL cholesterol levels, patient satisfaction with care, and patient-rated quality of care. RESULTS: After adjusting for case-mix differences across groups and plans, an average of one additional documented process of care for each patient in a group or plan was associated with significantly lower mean LDL cholesterol levels (-4.51 mg/dl [95% CI 1.46-7.58]) but not with A1C, SBP, or HDL cholesterol levels. The number of care processes documented was associated with patient satisfaction measures and self-rated quality of diabetes care. CONCLUSIONS: Variation in the number of simple process-of-care indicators across provider groups or health plans is associated with differences in patient-centered measures of quality, but assessment of the quality of cardiometabolic risk factor control will require more advanced clinical performance indicators.

Aged↗

Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors.

Rimonabant is the first selective blocker of the cannabinoid CB1 receptors being developed for the treatment of obesity, tobacco smoking and cardiometabolic risk factors. Following 1 year of treatment, rimonabant 20 mg/day leads to greater weight loss compared with placebo. Therapy with rimonabant is also associated with favourable changes in serum lipids and an improvement in glycaemic control in Type 2 diabetics. At the same dose, rimonabant significantly increases the cigarette smoking quit rates compared with placebo. Rimonabant appears to be generally well tolerated, with primary side effects of mild nausea, diarrhoea, anxiety and depression. As an agent with a novel mechanism of action, rimonabant has the potential to be a useful adjunct to lifestyle modification in the treatment of obesity, metabolic syndrome and cigarette smoking.

Animals↗

Polygenic scores capture genetic modification of the adiposity-cardiometabolic risk factor relationship.

Polygenic scores (PGSs) that can predict response to interventions can facilitate precision medicine and are detectable in observational datasets as PGS-by-exposure (PGS&#xd7;E) interactions. PGSs based on interactions (iPGSs) or variance effects (vPGSs) may be more powerful than standard PGSs for detecting PGS&#xd7;E, but these have yet to be systematically compared. We describe a generalized pipeline for developing and comparing these PGS types and apply it to detect genetic modification of the relationship between adiposity (measured by BMI) and a broad set of cardiometabolic risk factors. Our applied analysis in the UK Biobank identified significant PGS&#xd7;BMI for 16/20 risk factors, most consistently for the iPGS approach. Many interactions replicated in All of Us (AoU); for example, we observed a 72% larger BMI-alanine aminotransferase association in the top iPGS decile in AoU. Our study provides a framework for the comparison of PGS&#xd7;E strategies and informs efforts toward clinically useful response-focused PGSs.

Humans↗

Evaluating and treating cardiometabolic risk factors: a case discussion.

Reducing the risk for coronary heart disease (CHD) requires a comprehensive assessment of cardiometabolic risk factors along with the initiation of nonpharmacologic and pharmacologic therapies to mitigate these risk factors. A case study is presented to illustrate the approach to evaluating a patient and selecting among available and emerging therapeutic modalities to reduce CHD risk.

Angiotensin-Converting Enzyme Inhibitors↗

Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men.

OBJECTIVE: The link between excess intra-abdominal adiposity (IAA) and metabolic complications leading to type 2 diabetes and cardiovascular disease is well recognized. Blockade of endocannabinoid action at cannabinoid CB(1) receptors was shown to reduce these complications. Here, we investigated the relationship between IAA, circulating endocannabinoid levels and markers of cardiometabolic risk in male obese subjects. DESIGN, SUBJECTS AND MEASUREMENTS: Fasting plasma levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), were measured by liquid chromatography-mass spectrometry in a study sample of 62 untreated asymptomatic men with body mass index (BMI) from 18.7 to 35.2 kg/m(2). RESULTS: Plasma 2-AG, but not AEA, levels correlated positively with BMI, waist girth, IAA measured by computed tomography, and fasting plasma triglyceride and insulin levels, and negatively with high-density lipoprotein cholesterol and adiponectin levels. Obese men with similar BMI values (> or =30 kg/m(2)) but who markedly differed in their amount of IAA (< vs > or = 130 cm(2), n=17) exhibited higher 2-AG levels in the presence of high IAA. No difference in 2-AG concentrations was observed between obese men with low levels of IAA vs nonobese controls. CONCLUSIONS: These results provide evidence for a relationship in men between a key endocannabinoid, 2-AG, and cardiometabolic risk factors, including IAA.

Adiponectin↗

[Impact of endocannabinoid system in modulation of cardiometabolic risk factors].

Endocannabinoid system, the complex of specific cannabinoid receptors (CB1 and CB2 subtypes) and their endogenous agonistic ligands (endocannabinoids) plays, besides others, an important role in the central and peripheral regulation of food intake, fat accumulation, and lipid and glucose metabolism. Alterations of these functions are associated with endocannabinoid system hyperactivity. The cannabinoid receptor CB1 antagonist rimonabant normalizes the over activated endocannabinoid system which contributes to the regulation of energy homeostasis, and improves lipid and glucose metabolism--decreases body weight, waist circumference, intra-abdominal obesity and triglycerides, increases HDL-C, improves insulin sensitivity according to HOMA index. Results of the international multicentric clinical trials confirm that rimonabant is well tolerated and show antiatherogenic effects (increased adiponectin, decreased marker of inflammation CRP and improvement of LDL profile) as well as decreased percentage of subjects with NCEP/ATPIII (National Cholesterol Education Program Adult Treatment Panel III) defined metabolic syndrome. Thus, the CB1 cannabinoid receptor antagonist rimonabant is suggested to be a prospective drug decreasing cardiometabolic risk factors.

Cannabinoid Receptor Antagonists↗

Contemporary strategies for managing cardiometabolic risk factors.

OBJECTIVE: To review the metabolic syndrome as defined by the 2001 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) and its modifiable risk factors and to review currently available treatment modalities. SUMMARY: Metabolic syndrome, although still controversial, is a growing concern. Most definitions include elevated blood pressure, smoking, inflammation, insulin resistance, abdominal adiposity, elevated blood glucose, and atherogenic dyslipidemia as modifiable risk factors. Some researchers believe that additional signs of inflammation such as plasminogen activator inhibitor-1 and C-reactive protein should be added to this list. Current treatment options include lifestyle changes (diet and exercise), pharmacotherapy, and bariatric surgery. The endocannabinoid system appears to play a key role in metabolism and weight gain. The investigational agent rimonabant is a cannabinoid receptor type 1 blocker that has been employed in numerous trials involving more than 6,500 patients. It has led to significant weight loss, reduced central fat, and improved glycemic and lipid profiles.

Abdomen↗

The cardiometabolic syndrome as a cardiovascular risk factor.

The cardiometabolic syndrome (CMS) is associated with cardiovascular disease (CVD) and includes a constellation of risk factors such as central obesity, hypertension, insulin resistance, dyslipidemia, microalbuminuria, and hypercoagulability. Collectively, these risk factors increase CVD endpoints such as stroke, congestive heart failure, chronic kidney disease (CKD), and overall mortality. The CMS is associated with endothelial dysfunction, inflammation, abnormal thrombolysis, and increased oxidative stress that accentuate progression of CVD. We will review how the varying components of the CMS relate to an increased CVD and renal disease risk.

Dyslipidemias↗

Proteome organ aging and cardiometabolic risk in a population at risk for heart failure.

BACKGROUND: Biological aging varies across individuals and tissues, influencing chronic diseases, including heart failure (HF). Emerging proteome techniques enable quantification of organ-specific aging acceleration (OAA), but whether OAA relates to HF severity and differs by sex remains unclear. We aim to assess the sex-related association between OAA of heart, artery and kidneys and HF severity, and to investigate relevant cardiometabolic risk factors of organ aging. METHODS: In 556 participants from the HELPFul cohort, we estimated predicted biological age for heart, artery, and kidneys using plasma proteomics and calculated OAA as the deviation from chronological age. Associations between OAA and HF stage, echocardiographic parameters, and cardiometabolic risk factors were evaluated using regression models. Composite indices, including triglyceride-glucose body mass index (TyG-BMI), c-reactive protein-triglyceride glucose index and triglyceride-to-HDL cholesterol ratio were assessed for associations with advanced OAA. RESULTS: Mean age was 63&#x2009;&#xb1;&#x2009;9&#xa0;years; 65% were women. Patients were classified as HF stage A (35%), B (29%) and C/D (36%). Heart OAA was significantly associated with advanced HF (Stage C/D) in both sexes (OR&#x2009;=&#x2009;1.12, 95% CI 1.03 to 1.23 in women; OR&#x2009;=&#x2009;1.18, 95% CI 1.05 to 1.32 in men), while artery OAA was linked to HF only in women (OR&#x2009;=&#x2009;1.10, 95% CI 1.01 to 1.18). Multi-organ aging (&#x2265;&#x2009;2 organs with advanced OAA) conferred over three-fold higher odds of being in Stage C/D. Heart OAA correlated with impaired cardiac structure and function, particularly reduced ejection fraction in men and increased left ventricular mass index in both sexes. Diabetes emerged as the most relevant factor of artery and kidney OAA. TyG-BMI was significantly associated with advanced kidney OAA, only in women (z-scored OR&#x2009;=&#x2009;1.88, 95% CI 1.45 to 2.45). CONCLUSIONS: Proteome-derived organ aging correlates with HF severity, with possible sex-related patterns. Diabetes and higher TyG-BMI are associated with faster organ aging, which may reflect shared aging mechanisms between metabolic dysfunction and HF.

Humans↗

Role of the pharmacist.

The prevalence of cardiovascular risk factors continues to rise, with considerable emphasis on the upward trends in obesity and diabetes mellitus, which have increased by 46% and 60%, respectively, in the past 10 years. The alarming increase in the prevalence of diabetes and obesity has resulted in the development of new and innovative drug therapies to assist in managing cardiometabolic risk factors. This advent creates many opportunities for pharmacists to evaluate patients' drug regimens and influence lifestyle modification. Drug therapy management programs allow pharmacists to take active roles in assessing drug regimens and to intervene as appropriate. No matter what their practice environment, pharmacists have numerous opportunities to recognize and recommend treatment for cardiometabolic risk factors and to increase patient compliance by educating patients and health care practitioners.

Cardiovascular Diseases↗