High CVD Risk Research Articles

Age-stratified comparison of heart age and predicted cardiovascular risk in 370 000 primary care patients

BackgroundCardiovascular disease (CVD) preventive medications are recommended for patients at high short-term CVD risk. As most younger people with multiple raised CVD risk factors levels have low short-term risk, they...

Abstract 4138647: Opportunistic Screening for Cardiovascular Risk Using Chest X-Rays and Deep Learning: Associations with Coronary Artery Disease in the Project Baseline Health Study and Mass General Brigham Biobank

Introduction/Background: We previously demonstrated that an open-source deep learning model (CXR-CVD Risk) can predict 10-year major adverse cardiovascular events (myocardial infarction&stroke), based on a chest radiograph image (CXR). As deep learning models are black boxes, establishing the biological processes the model captures to predict risk may help build understanding and trust in the model. Research Questions/Hypothesis: To test associations between deep-learning derived CXR-CVD Risk and markers of cardiovascular disease including coronary artery calcium (CAC) and stenosis ≥50% on CT, systolic blood pressure (SBP), ankle brachial index (ABI), and prevalent myocardial infarction and stroke. Methods/Approach: We conducted external validation of CXR-CVD-Risk in two cohorts: 1) 2,097 volunteers in the Project Baseline Health Study (PBHS) and 2) 1,644 Mass General Brigham Biobank (MGBB) patients. The CXR-CVD-Risk model estimated 10-year cardiovascular event risk (probability between 0 and 1) from a CXR image. We calculated linear associations with SBP, ABI, and the logarithm of coronary artery calcium and odds ratios for prevalent hypertension, myocardial infarction, stroke, and, in the MGBB, coronary artery stenosis ≥50%. Analyses were adjusted for age, BMI, sex, smoking status, and enrolling site. Results/Data: CXR-CVD-Risk was associated with CAC in both populations (PBHS: 1.11-fold increase, 95% CI: [1.07-1.16]; MGBB: 1.03-fold increase [1.01-1.05] in CAC per 1% increase in CXR-CV-Risk). CXR-CVD-Risk was also associated with SBP (0.59 mmHg increase [0.24-0.93] in SBP per 1% increase in CXR-CV-Risk), history of hypertension, history of myocardial infarction, and stroke. There was an inverse association with ABI (0.010 decrease [0.005-0.014] in ABI) in the PBHS. In the MGBB, CXR-CVD-Risk was associated with coronary artery stenosis ≥50% (OR = 1.004 [1.002-1.007]). All estimates are after covariate adjustment. Conclusion: This deep learning CXR risk score was associated with coronary artery disease (calcium score and stenosis ≥50%), CVD risk factors, and prevalent CVD. Opportunistic screening using CXRs in the electronic record can identify patients at high risk of CVD who may benefit from prevention.

Abstract 4137559: Assessing Veterans’ Risk of Cardiovascular Disease by Gender Identity

Background: Extant literature suggests that transgender and gender diverse (TGD) individuals experience a higher burden of CVD risk factors and psychosocial stressors than their cisgender (cis) peers. However, prior studies have been limited by self-reported outcomes or small samples. Aim: To determine whether TGD veterans have greater CVD (MI, ischemic stroke, cardiac revascularization) incidence than cis veterans using large, nationwide data. Methods: We used EHR data from the Veterans Healthcare Administration to identify veterans with >2 outpatient encounters in fiscal years 2010-2019. Veterans’ gender identity was classified using natural language processing in combination with gender-affirming hormone therapy (GAHT) and a previously validated algorithm for identifying TGD individuals using ICD codes and VHA data. Of 1,105,082 veterans without prior CVD, 42,149 were classified as TGD. We examined sample characteristics by gender identity and used Cox regression to assess the association of gender identity with incident CVD. Results: TGD veterans’ mean age (years) was 46 (cis females=40; cis males=53). Cis females had the fewest CVD risk factors, followed by TGD veterans and cis males. Adjusting for age, race, and Hispanic ethnicity, TGD veterans had 1.49 [1.42-1.56] and 0.93 [0.90-0.97] times the risk of CVD compared to cis females and cis males, respectively. Upon additional adjustment for other CVD risk factors, renal function, alcohol use disorder, depression, anxiety, and sexual minority status, results remained statistically significant. Significance also held in sensitivity analyses which matched each TGD veteran to cis female and male veterans on age within 2 years. In analyses stratified by gender identity, trans feminine (HR [95% CI]: 1.26 [1.14-1.40]) and uncategorized TGD veterans (HR [95% CI]: 1.29 [1.22-1.37]) were at higher CVD risk than cis female veterans; trans masculine (HR [95% CI]: 0.85 [0.77-0.93]) and trans feminine veterans (HR [95% CI]: 0.90 [0.82-0.99]) were at lower CVD risk than cis male veterans. Among TGD veterans, GAHT receipt was associated with an 11% decrease in CVD risk. Conclusion: TGD veterans’, particularly trans feminine and uncategorized TGD veterans’, CVD risk was greater than that of cis females. Contrary to prior findings, GAHT was associated with decreased CVD risk. These results invite further study into the mechanisms by which GAHT and other factors impact CV health across and within gender identities.

Abstract 4112589: Typology of Self-Care in Adults with Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Introduction: Individuals with type 1 diabetes (T1D) complicated by impaired awareness of hypoglycemia (IAH) are at significantly increased risk for severe hypoglycemia: a marker of high risk of CVD. Tailoring interventions to promote hypoglycemia avoidance is difficult due to self-care heterogeneity among those with T1D. Aims: Map self-care heterogeneity among adults with T1D into behavioral phenotypes and identify common barriers to hypoglycemia avoidance within each phenotype. Methods: An explanatory sequential mixed methods study was performed in 200 adults with T1D. Participants reported personal, clinical, and social determinants of health, hypoglycemia awareness, and self-care of diabetes (Self-Care of Diabetes Inventory, scored 0-100, adequate ≥70) . Cluster analysis was performed to identify self-care clusters. Then, directed content analysis was applied to individual, semi-structured interviews performed in a subsample from each cluster with IAH ( n =20). Findings were integrated to develop a typology of self-care and identify barriers to hypoglycemia avoidance within each phenotype. Results: Three self-care phenotypes were identified. Experts ( n =70; mean age: 45±17 years; 24% Black; T1D duration: 25±16 years; HbA 1c : 7.36±1.67%; IAH: 20%) performed all aspects of self-care adequately (Maintenance: 84.9±8.8; Monitoring: 85.1±8.8; Management: 72.5±10). Yet, Experts with IAH reported purposefully delaying treatment of hypoglycemia due to lack of concern. Those with Inconsistent self-care ( n = 112; mean age 37±14 years; 20% Black: T1D duration: 21±13 years; HbA 1c : 7.26±1.16%; IAH: 30%) performed only self-care maintenance adequately (Maintenance: 78.6±8.9; Monitoring: 65.6±9.8; Management: 56.8±10.1). Those with Inconsistent self-care and IAH reported passive self-care monitoring that inhibited effective hypoglycemic management. Novices ( n = 18; mean age 27±7 years; 50% Black: T1D duration: 16±8 years; HbA 1c : 8.97±2.80%; IAH: 28%) reported difficulty performing all aspects of self-care (Maintenance: 51.9±7.7, Monitoring: 56.9±12.9, Management: 44.5±6.3) due to economic and psychosocial barriers. Conclusions: Self-care heterogeneity mapped onto three phenotypes that can be used to better understand patient barriers to hypoglycemia avoidance and hypoglycemia awareness restoration. This typology provides a framework for investigating how best to tailor IAH treatment considerate of self-care.

Predictive markers of early endothelial dysregulation in type-1 diabetes: a meta-analysis.

This study identifies a new set of salient risk factors that may trigger danger signals of vascular dysregulation in T1D. Vascular abnormalities and impairment of CVD is a major adverse effect of T1D, particularly affecting children, adolescents and young adults. The patients of T1D were compared with the healthy control (HC) for the risk factors of vascular dysregulation in published studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, relevant to clinical subjects. A random effects model was followed and analysed by RevMan 5.4 and GraphPad Prism software. 80 relevant case-control studies having 7492 T1D patients and 5293 HC were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of < 40 years were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-c, AI%, sICAM-1, and FMD% which could be evaluated with a simple blood test or non-invasive techniques. These may serve dual purposes as biomarkers of rapid diagnosis that could offer prospective tailor-made therapeutics for T1D. (Protocol registered at https://www.crd.york.ac.uk/prospero/CRD42022384636 ).

The prevalence, patients characteristics and risk factors of hyper-Lp(a)-emia in the Polish population. The first results from the PMMHRI-Lp(a) Registry

Abstract Background Based on the recent data and existing guidelines Lp(a) is recognized, independent CVD risk factor. However, the knowledge on the prevalence of elevated Lp(a) levels, patients characteristics as well as non-genetic risk factors is scarce from some world regions including from Poland, the largest CEE country. Purpose We aim to present the first results from the Lp(a) registry established in the 2nd largest hospital in Poland - Polish Mother’s Memorial Hospital Research Institute (PMMHRI). Methods The PMMHRI-Lp(a)-Registry was established in 2022. The indications for Lp(a) measurement in the registry are based on the 2021 Polish Lipid Guidelines and new Polish recommendations on the management with elevated Lp(a) (2024). The PMMHRI-Lp(a)-Registry is a part of the being founded Lp(a) National Registry of the Polish Lipid Association. Results Based on the data from 302 consecutive patients (mean age 52.18 years; women 53%) the mean Lp(a) level was 30.3±39.4 mg/dl; it was numerically higher in woman (32.8 mg/dl), but there were no significant sex differences (men: 27.5 mg/dl; p=0.245). There were also no significant differences between those with and without CAD, stroke, HF, cancer, diabetes, kidney disease, and thyroid disease. The significant Lp(a) level difference was observed in those with diagnosed dyslipidemia in comparison to those without (31.9±40.6 vs 17.7±25.8 mg/dl, p=0.044) and in those with the history of myocardial infarction (MI) vs those without (50.1±50.3 vs 28.1±37.5 mg/dl, p=0.004). However, when we divided those with MI on premature vs no premature, no significant difference in Lp(a) level was observed (41,6±41.9 vs 57.6±56.7 mg/dl, p=0.39). Lipid lowering therapy did not significantly affect Lp(a) level, with only significant differences in those treated with ezetimibe (as a part of the combination therapy; 39.5±47.6 vs 27.5±36.3 mg/dl, p=0.027). For selected patients (n=31; 10.3%) with two Lp(a) measurements (mean time distance: 7±5 months) we did not observe any significant visit-to-visit variability (mean difference: 0.81 mg/dl; z=0.256, p=0.262) (Fig. 1). We did not also observe any percentage differences in variables (besides MI history, p=0.017) for different Lp(a) risk groups: 0-30, &amp;gt;30-50, &amp;gt;50-180 and &amp;gt;180 mg/dl. While dividing the population on those with Lp(a) ≤30 mg/dl vs &amp;gt;30 mg/dl, the only differences were seen for dyslipidemia diagnosis (p=0.044) and MI occurrence (6.98 vs 17.24%; p=0.007). Similar pattern was observed while dividing the whole population on those with Lp(a) ≤50 vs &amp;gt;50 mg/dl (Fig. 2). Conclusions These results strongly emphasize that Lp(a) should be measured commonly, as its high level is highly prevalent in patients at the risk both in primary and secondary prevention, what require risk re-stratification and treatment optimization. This is especially important in the regions that characterize of baseline high CVD risk, what refers to most of the CEE countries, including Poland.

7184 Type 2 Diabetes As An Independent Risk Factor For Increased Incidence Of Cardiovascular Events In Patient With Nonalcoholic Fatty Liver Disease

Abstract Disclosure: E. Roh: None. K. Son: None. H. Jung: None. J. Huh: None. S. Lee: None. S. Ihm: None. K. Han: None. J. Kang: None. Background: Although coexistence of type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD) has been linked to unfavorable metabolic profile and an increasing cardiovascular risk, the impact of T2DM on the risk of developing CVD within the context of NAFLD remains unclear. This study aimed to investigate long-term CVD outcomes in patients with NAFLD according to glycemic status using nationwide cohort of Korean adults. Methods: This retrospective, longitudinal study included 1,057,775 patients with NAFLD, who had participated in the national health screening in 2009 and were followed up until 2020. The baseline glycemic status was divided into three categories [normal fasting glucose (NFG), impaired fasting glucose (IFG) and T2DM]. Cox proportional hazards models were used to assess the association of glycemic status with incident CVD. Results: During a median follow-up period of 10.3 years, 26,491 cases of MI, 55,791 cases of stroke, and 11,147 cases of CV death were identified. After adjusting for possible covariates, participants with T2DM had a higher risk of CVD, with hazard ratios of 1.394 (95% CI 1.351−1.439) for MI and 1.391 (95% CI 1.362−1.420) for stroke, and 1.457 (95% CI 1.392−1.524) for CV mortality, compared to those with NFG. The increased risk of CVD attributable to T2DM was more profound among individuals with fewer conventional CVD risk factos, including younger age, not obese, and the absence of hypertension. Conclusions: These results suggest that the identification of T2DM in individuals of NAFLD may help the prediction of future progression of CVD. Presentation: 6/3/2024

The impact of perception bias for cardiovascular disease risk on physical activity and dietary habits

ObjectiveCardiovascular disease (CVD) remains a significant public health challenge in China. Accurate perception of individual CVD risk is crucial for timely intervention and preventive strategies. This study aims to determine the alignment between CVD risk perception levels and objectively calculated CVD risk levels, then investigate the disparity in physical activity and healthy diet habits among distinct CVD risk perception categories. MethodsFrom March to August 2022, a cross-sectional survey was conducted in Zhejiang Province using convenience sampling. Participants aged between 20 and 80 years, without prior diagnosis of CVD were included. CVD risk perception was evaluated with the Chinese version of the Attitude and Beliefs about Cardiovascular Disease Risk Questionnaire (ABCD-C), while objective CVD risk was assessed through the Prediction for Atherosclerotic Cardiovascular Disease Risk (China-PAR) model. Participants’ demographic information, self-reported physical activity, and healthy diet score were also collected. ResultsA total of 739 participants were included in the final analysis. Less than a third of participants (29.3%) accurately perceived their CVD risk, while 64.5% over-perceived it and 6.2% under-perceived it. Notably, half of the individuals (50.0%) with high CVD risk under-perceived their actual risk. Compared to the accurate perception group, individuals aged 60-80 years old (OR = 6.569), currently drinking (OR = 3.059), and with hypertension (OR = 2.352) were more likely to under-perceive their CVD risk. Meanwhile, participants aged 40-<60 years old (OR = 2.462) and employed (OR = 2.352) were more likely to over-perceive their risk. The proportion of individuals engaging in physical activity was lowest in the under-perception group, although the difference among the three groups was not statistically significant (χ2=2.556, P=0.278). In addition, the proportion of individuals practicing healthy diet habits was also lowest in the under-perception group, and a significant statistical difference was observed among the three groups (χ2=10.310, P=0.006). ConclusionOnly a small proportion of participants accurately perceived their CVD risk, especially among those with high actual CVD risk. Individuals in the under-perceived CVD risk group exhibited the lowest rates of physical activity engagement and healthy diet adherence. Healthcare professionals should prioritize implementing personalized CVD risk communication strategies tailored to specific subgroups to enhance the accuracy of risk perception.

Association between changes in high-density lipoprotein cholesterol and risk of cardiovascular disease

BackgroundThe present study was performed to determine the association between changes in the HDL-C concentration and incident CVD. MethodsTime-dependent Cox regression models were used to evaluate the association between changes in the HDL-C concentration and the risk of incident CVD. Participants were followed up from 2015 to 2021. ResultsIn total, 24,123 participants with a median follow-up of 4.26 years were analyzed, and the mean age of the cohort was 56.24 years, 57.8 % were female, 24.3 % were current smokers, and 12.8 % had a history of alcohol use. Low, normal, and high HDL-C was defined as <40, 40–80, and >80 mg/dL, respectively. The average time for the two HDL-C measurements was 2.8 years,compared with participants whose HDL-C was maintained at a normal level, the risk of CVD was higher in those whose HDL-C changed to a low level, remained unchanged at a low level(HR, 1.24; 95 % CI, 1.01–1.40,P < 0.001), similarly, the risk of CVD was higher in those whose HDL-C changed from very high level to normal level(HR, 0.81; 95 % CI, 0.67–0.99,P = 0.039). Also compared with participants whose HDL-C was maintained at a normal level, the risk of CVD was lower in those whose HDL-C increased from low to normal and high(HR, 0.80; 95 % CI, 0.66–0.98,P = 0.029). ConclusionsParticipants whose HDL-C changed to a low level and whose low HDL-C level was maintained had a higher risk of CVD, whereas participants whose HDL-C changed from low to high had a lower risk of CVD.

Abstract P425: Role of 24h UNaK ratio in patients with hypertension and resistant hypertension by gender and race

RHTN is defined as blood pressure above goal despite using ≥3 antihypertensive medications. Patients with RHTN are at an increased risk for CVD compared to those with more easily controlled hypertension (HTN). High sodium intake and higher 24h urinary (U) sodium (Na) potassium(K) ratio is associated with higher CVD risk. The role of this ratio in RHTN has not been investigated. Methods: We conducted a cross-sectional analysis of a large cohort of 2397 black and white patients with RHTN who were referred to the RHTN Clinic at the University of Alabama at Birmingham and who underwent a 24h urine collection. Patients with HTN served as a control group. Results: Patients with RHTN had significantly higher 24h UNaK ratio than patients with HTN (3.2±1.6 vs 3.6 ±2.0, p &lt;0.001 ) and had an earlier onset of HTN (38.8±13.7 years (yrs) vs 47.6±16.2 yrs, p=0.001) and longer duration 17.6±11.2 vs 12.0±10.7 yrs, p=0.001), higher BMI (32.6±7.2 vs 29.98±6.5 kg/m2), and 24-hourUNa (181±88 vs 164±77 mmol, p=0.01). Within the RHTN group (n=1340) females had a significant higher 24h UNaK ratio than males (3.5±1.9 vs 3.2±1.7, p =0.006) and blacks had a significant higher 24h UNaK ratio than whites (3.0±1.6 vs 3.9±2.0, p&lt;0.001). Conclusion: Higher 24h UNaK ratio as index of higher sodium and lower potassium intakes were found in patients with RHTN as well as resistant hypertensive females and blacks and may explain certain higher CV risks in these populations.

Abstract P218: Resistant hypertension is associated with elevated 24-hour cortisol to cortisone ratios in black patients.

Background: RHTN is defined as blood pressure above goal despite using ≥3 antihypertensive medications. Patients with RHTN are at an increased risk for cardiovascular (CVD) compared to those with more easily controlled hypertension (HTN). Blacks With RHTN are at a specifically high risk for CVD. Mineralocorticoid receptor activation has been found as an important mechanism of RHTN. However, aldosterone levels are not different in blacks versus whites. The role of 24-hour cortisol-to-cortisone ratios in this group has not been investigated. Methods: We conducted a cross-sectional analysis of a large cohort of 2397 black and white patients with RHTN who were referred to the RHTN Clinic at the University of Alabama at Birmingham and who underwent 24-hour urine collection including cortisol and cortisone. Patients with HTN served as a control group. Results: Black patients with RHTN compared to whites had a trend to higher 24h cortisol levels (17.7±27.6 vs 16.9±14.9, p =0.70, significantly lower 24h cortisone levels (60.45±37.7 vs 75.3±40.0, p 0.000234), and significantly higher 24h cortisol-to-cortisone ratios (0.23±0.14 vs 0.20 ±0.10, p=0.027). They were younger (53.3±11.6 vs 59.4±12.9 years), more obese (BMI 34.9±7.6 vs 30.8±6.1 kg/m2, p&lt;0.001), had earlier onset of HTN (35.6±12.5 vs 41.4±11.6 years of age, p&lt;0.001), higher 24-hour urinary sodium excretion (188.2±92.5 vs 174.9±83.1 mmol, p=0.006) and lower potassium excretion (54.5 ±28.6 vs 65.5 ±30.5 mmol, p&lt;0.001). Furthermore, they had a significantly higher rate of heart failure (p=0.000455) and diabetes (p=0.0006). Conclusion: Cortisol dysregulation and a higher cortisol-to-cortisone ratio as an index of 11beta HSD2 activity may play a role in black patients with RHTN and may be related to adverse outcomes in this population.

Abstract 26: An Effective mHealth Intervention to Close the Guideline-to-Practice Gap in Hypertension Treatment: mGlide RCT

Background: Suboptimal HTN control is a widespread problem particularly among minorities and socioeconomically disadvantaged groups. Objective: To determine if a mobile health (mHealth) intervention facilitating an active partnership between inter-professional care teams (including pharmacists) and patients improves HTN control in patients with uncontrolled HTN. Methods: mGlide is an NIH-funded, 2-arm RCT evaluating HTN control between a mHealth intervention (mGlide) vs. state-of-clinical-care (comparison) groups using a PROBE (Prospective Randomized Open Blinded End-point) design. Table 1 shows intervention components. High CVD risk patients with uncontrolled HTN identified by EHR query were randomized 1:1 to either mGlide or to comparison for a 6-month intervention followed by a 6-month observation period. Recruitment sites include primary care clinics and specialty stroke service in an integrated health system, community clinics (CC) and federally qualified health centers (FQHC). The FQHC and CC serve low income and minority (Hmong and Latino) patients. The primary aim tested clinical effectiveness of mGlide in reducing SBP at 6 months. Secondary outcomes include resource utilization, adverse events and medication side-effects. Results: Recruitment started in 2019. N=395 participants enrolled by August 2023. The pandemic impacted enrollment; however enrollment recovered after vaccine availability (Figure). Primary outcome was available in March 2024 on everyone except in those lost to follow-up (n=38; 9.6%). We used multiple imputation for those missing 6 month SBP. Baseline mean SBP was 143.2 vs. 143.6 mm Hg in mGlide vs. comparison. The intervention led to better HTN control (Table 2). Mean 6-month SBP was 128.1 (mGlide) vs. 134 mm Hg (comparison). Adjusting for baseline SBP and study strata, 6-month mean SBP was 5.7 mm Hg (95% CI 2.9-8.4; p = 0.0001) lower in mGlide vs. comparison. The odds of HTN control defined as “alive and SBP &lt; 130 mm Hg”, was 60% higher in the mGlide arm (OR 1.6; 95% CI 1.03-2.48; p=0.035). There was one death in each study arm. The mGlide arm had fewer ER visits (16% vs. 25%; p=0.024), fewer hospitalizations (7% vs. 13%; p=0.044) and more medication side effects (39% vs. 26%, p=0.008). Conclusions: An inexpensive mHealth intervention that used the patient’s own phone (Table 1) was implemented in diverse health systems and significantly reduced SBP and was associated with less resource utilization at 6 months (Table 2).

Risk analysis of blood pressure changes on cardiovascular disease in Chinese population.

The study aimed to assess the impact of changes in blood pressure on cardiovascular events in the Chinese population. It enrolled 33 179 Chinese participants aged ≥35 years (57.1% women) without CVD at baseline. BP status was defined according to the 2017 ACC/AHA hypertension guidelines. The type of BP change was defined as change in BP status from baseline to the end of follow-up, included stable BP<130/80, <130/80 to ≥130/80, ≥130/80 to<130/80mm Hg, persistent BP ≥130/80mm Hg. The hazard ratio (HR) of incident CVD by change in BP category was estimated using Cox proportional hazards and Fine-Gray models. During median follow-up of 3.17 years, 2023 CVD events occurred. Compared with BP<120/80, 120-129/<80mm Hg at baseline (HR=1.66, 95% CI: 1.09-2.53), 130-139/80-89mm Hg (HR=1.35, 95% CI: 0.94-1.95), and ≥140/90mm Hg (HR=2.46, 95% CI: 1.78-3.40) were risk factors for CVD. Compared with the group with stable BP<130/80mm Hg, the risk of CVD was 1.88 (95% CI: 1.40-2.53) in the group with persistent BP ≥130/80mm Hg and 1.40 (95% CI: 1.01-1.94) in the group of BP decreased to<130/80mm Hg. These results showed that BP 120-129/<80, 130-139/80-89, and ≥140/90mm Hg were associated with a high risk of CVD. Over time, persistent BP ≥130/80mm Hg increased the risk of CVD, but a return to<130/80mm Hg from hypertension decreased the risk of CVD.

Phenotyping lipid profiles in type 2 diabetes: Risk association and outcomes from the Cardiovascular Health Study

AimsTo determine whether discrete lipid profiles (refer to as lipid phenotyping) can be used to stratify cardiovascular risk in individuals with type 2 diabetes. Methods and resultsCardiovascular Health Study participants with diabetes and fasting lipid profiles at baseline (n = 866) were categorized separately by level of LDL cholesterol and HDL-C/Triglyceride (Tg) profiles (low Tg/high HDL-C; high Tg/low HDL-C; high Tg only or low HDL-C only). We performed Cox multivariate regression analysis to assess the risk of CVD mortality, incident myocardial infarction (MI), heart failure (HF), stroke, and composite MACE (MI, HF, stroke, and CVD mortality) associated with each lipid category. We also calculated risk estimates for MACE using lipid measures as continuous variables. In the fully adjusted model, the high triglyceride plus low HDL-C cholesterol phenotype demonstrated risk that was at least as high as the highest LDL-C sub-group phenotype for CVD mortality (Hazard ratio {HR} 1.58 vs 1.48), MI (HR 1.53 vs 1.58), HF (HR 1.47 vs 1.20), stroke (HR 2.02 vs 1.43), and MACE (HR 1.58 vs 1.38). When modeled continuously, the HR per SD for MACE was 1.12 (p = 0.03) for LDL-C and 1.19–1.20 (p < 0.001) for triglycerides or remnant cholesterol. ConclusionsParticipants with the high triglyceride/low HDL-C phenotype had equivalent or higher CVD risk than those with the high LDL-C phenotype. Further studies are necessary to determine whether lipid phenotyping accounts for the substantial CVD risk not explained by LDL cholesterol among individuals with type 2 diabetes.

Physical Activity and Urinary Sodium Excretion Circadian Rhythm: A Population-Based Cross-Sectional Pilot Study.

Background/Objectives: Blood pressure (BP) is characterized by a circadian rhythm (Circr) with lower nighttime values, called dipping. Non-dipping is associated with higher CVD risk. The Circr of urinary sodium excretion (NaCle), peaking during the day, is linked to BP patterns. Physical activity (PA) is known to improve BP control and enhance the dipping phenomenon, but its possible effect on NaCle remains unclarified. This study aimed to investigate the correlation between PA and the Circr of NaCle and to determine if the relationship is independent of age, sex, BP values, dipping pattern, and salt intake. Methods: A pilot cross-sectional analysis was conducted using data from the Ticino Epidemiological Stiffness Study, involving 953 participants in Switzerland. Data collection included standardized questionnaires, blood samples, 24 h urine collections, and ambulatory BP monitoring. Participants were categorized into sedentary, partially active, and active. The effect of PA, NaCl intake, and dipping on the day/night NaCle ratio was assessed with multivariable linear regressions. Results: Participants' median age was 49 years, with 78% having normal BP values and 47% exhibiting a dipping pattern; 51% were classified as sedentary and 22% as partially active. The median NaCl intake was 7.9 g/day. The youngest subjects had a higher hourly NaCle ratio compared to older subjects. Higher NaCl intake correlated with increased BP, a phenomenon more pronounced in men and younger subjects. The hourly day/night NaCle ratio positively correlates with dipping; however, PA did not show a significant correlation with the NaCle ratio. Conclusions: This study indicates that while the day/night NaCle ratio correlates with the dipping pattern, PA is unrelated to the circadian rhythm of renal sodium handling. The beneficial effects of PA on BP and cardiovascular health thus appear to be mediated through mechanisms other than NaCle. These are explorative findings only but relativize the need for further investigations on the topic.

Randomized, open-label, study comparing efficacy and safety of lerodalcibep to inclisiran in patients with CVD or at high risk for CVD requiring additional LDL-cholesterol reduction

Randomized, open-label, study comparing efficacy and safety of lerodalcibep to inclisiran in patients with CVD or at high risk for CVD requiring additional LDL-cholesterol reduction

Turk-heart: A study designed to determine strategies for achieving recommended dyslipidemia treatment goals in very high CVD risk patients in Turkey

Turk-heart: A study designed to determine strategies for achieving recommended dyslipidemia treatment goals in very high CVD risk patients in Turkey

Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial

Aims/hypothesisThe apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV).MethodsThis was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the ‘semaglutide’ group), or the combination of semaglutide and empagliflozin (referred to as the ‘combination-therapy’ group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico–medullary difference [ΔADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI.ResultsBoth semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: −0.20×10−3 mm2/s [95% CI −0.30, −0.10], p<0.001; empagliflozin: −0.15×10−3 mm2/s [95% CI −0.26, −0.04], p=0.01). No significant change was observed in the combination-therapy group (−0.05×10−3 mm2/s [95%CI −0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed ΔADC significantly from placebo, showing a decrease of −0.13×10−3 mm2/s (95% CI −0.22, −0.04; p=0.01). Compared with placebo, TKV decreased by −3% (95% CI −5%, −0.3%; p=0.04), −3% (95% CI −5%, −0.4%; p=0.02) and −5% (95% CI −8%, −2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA1c.Conclusions/interpretationIn a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis.Trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38Graphical

Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults–the CARDIA study

BackgroundThe black/white heart disease mortality disparity began increasing in the early 1980’s, coincident with the switch from sucrose to high-fructose-corn-syrup/(HFCS) in the US food supply. There has been more fructose in HFCS than generally-recognized-as-safe/GRAS, which has contributed to unprecedented excess-free-fructose/(unpaired-fructose) in foods/beverages. Average- per-capita excess-free-fructose, from HFCS, began exceeding dosages/(5-10 g) that trigger fructose-malabsorption in the early 1980’s. Fructose malabsorption contributes to gut-dysbiosis and gut-in-situ-fructosylation of dietary peptides/incretins/(GLP-1/GIP) which forms atherosclerotic advanced-glycation-end-products. Both dysregulate gut endocrine function and are risk factors for cardiovascular disease/(CVD). Limited research shows that African Americans have higher fructose malabsorption prevalence than others. CVD risk begins early in life.MethodsCoronary-Artery-Risk-Development-in-Adults/(CARDIA) study data beginning in 1985–86 with 2186 Black and 2277 White participants, aged 18–30 y, were used to test the hypothesis that HFCS sweetened beverage intake increases CVD risk/incidence, more among Black than White young adults, and at lower intakes; while orange juice-a low excess-free-fructose juice with comparable total sugars and total fructose, but a 1:1 fructose-to-glucose-ratio, i.e., low excess-free-fructose, does not. Cox proportional hazards models were used to calculate hazard ratios.ResultsHFCS sweetened beverage intake was associated with higher CVD risk (HR = 1.7) than smoking (HR = 1.6). CVD risk was higher at lower HFCS sweetened beverage intake among Black than White participants. Intake, as low as 3 times/wk, was associated with twice the CVD risk vs. less frequent/never, among Black participants only (HR 2.1, 95% CI 1.2–3.7; P = 0.013). Probability of an ordered relationship approached significance. Among Black participants, CVD incidence jumped 62% from 59.8/1000, among ≤ 2-times/wk, to 96.9/1000 among 3–6 times/wk consumers. Among White participants, CVD incidence increased from 37.6/1000, among ≤ 1.5-times/wk, to 41.1/1000, among 2 times/wk–once/d – a 9% increase. Hypertension was highest among Black daily HFCS sweetened beverage consumers.ConclusionThe ubiquitous presence of HFCS over-the-past-40 years, at higher fructose-to-glucose ratios than generally-recognized-as-safe, may have contributed to CVD racial disparities, due to higher fructose-malabsorption prevalence among Black individuals, unpaired/excess-free-fructose induced gut dysbiosis and gut fructosylation of dietary peptides/incretins (GLP-1/GIP). These disturbances contribute to atherosclerotic plaque; promote incretin insufficiency/dysregulation/altered satiety/dysglycemia; decrease protective microbiota metabolites; and increase hypertension, CVD morbidity and mortality.

Prevalence of very high cardiovascular disease risk in patients with type 2 diabetes mellitus: A population-based cross-sectional screening study.

The 2019 ESC/EASD guidelines categorize cardiovascular disease risk (CVD) in patients with diabetes mellitus (DM). Assessing CVD risk is necessary to identify individuals at very high risk of CVD, enabling tailored and precise intervention for this high-risk population. This study aims to evaluate the severity of a very high risk for CVD stratification among patients with type 2 DM (T2DM) across different regions in China. We conducted a cross-sectional screening study from 1 January 2020 to 30 December 2022. Disease duration, body mass index (BMI), targeted organ damage, such as atherosclerotic heart disease, proteinuria, impaired renal function, left ventricular hypertrophy, retinopathy and known CVD risk factors, were collected from diabetic patients by professionally trained physicians. The risk of CV in patients with DM was categorized into two groups: very high risk and others, according to the 2019 ESC/EASD guidelines. In total, 1 870 720 participants from 1669 hospitals in 30 provinces of China, excluding Tibet, Taiwan, Hong Kong and Macao, were enrolled from 2020 to 2022, among whom 67.50% of patients with T2DM were at very high risk for CVD. The proportions of very high-risk T2DM were higher in Northeast China (75.82%), Central China (73.65%) and Southwest China (72.66%), while the lowest prevalence of very high-risk T2DM was found in Southern China (60.15%). The multivariate binary logistic regression analyses suggested that the category of very high risk for CVD is associated with age [odds ratio (OR) = 1.04; 95% confidence interval (CI): 1.04-1.04; p < .0001], BMI (OR = 1.07; 95% CI: 1.07-1.07; p < .0001), duration of DM (OR = 1.05; 95% CI: 1.05-1.05; p < .0001), hypertension (OR = 3.75; 95% CI: 3.72-3.78; p < .0001), dyslipidaemia (OR = 5.22; 95% CI: 5.18-5.27; p < .0001) and smoking (OR = 2.92; 95% CI: 2.89-2.95; p < .0001). This study represented the largest observational study of CVD risk assessment in patients with T2DM in China. The CVD risk situation of patients with diabetes in China is critical, and comprehensive control and management of CVD risk factors, such as hypertension, BMI and dyslipidaemia, in patients with DM need to be strengthened in patients with T2DM in China.