Individual Cardiovascular Disease Risk Research Articles

The correlation between liver fibrosis and the 10‐year estimated risk of cardiovascular disease in adults with metabolic‐associated fatty liver disease: A cross‐sectional study in Vietnam

AbstractBackground and AimsMetabolic‐associated fatty liver disease (MAFLD) emerged as a novel term replacing nonalcoholic fatty liver disease (NAFLD) in 2020. While most MAFLD patients are asymptomatic, long‐term hepatic fat accumulation may lead to liver fibrosis and cardiovascular disease (CVD). Nevertheless, the relationship between MAFLD and cardiovascular (CV) risk factors remains unclear. This study aimed to assess the 10‐year estimated CVD risk in individuals diagnosed with MAFLD.MethodsBetween January 2022 and August 2023, this cross‐sectional study enrolled 139 MAFLD patients. We employed the systematic coronary risk evaluation 2 (SCORE2) and the systematic coronary risk evaluation 2–older persons (SCORE2‐OP) scoring systems to evaluate and categorize the 10‐year CV risk. Liver fibrosis was assessed using biochemical parameters (FIB‐4, AST/ALT, and APRI), and their correlation with CV risk was examined.ResultsMost MAFLD patients were categorized as having high or very high CV risk based on the SCORE2 and SCORE2‐OP. Liver fibrosis, measured by the FIB‐4 score, significantly differed among the various CV risk groups. Moreover, FIB‐4 correlated positively with SCORE2 and SCORE2‐OP (r = 0.588, p < 0.001), indicating its substantial predictive ability for identifying individuals at very high CV risk (AUC = 0.765, 95% CI: 0.686–0.845, p < 0.001). A FIB‐4 score of 1.275 demonstrated 81% sensitivity and 64% specificity in predicting very high CV risk among MAFLD patients.ConclusionPatients with MAFLD predominantly face high or very high CV risks, with elevated liver fibrosis associated with increased 10‐year estimated CVD risk. The FIB‐4 score exhibits promising predictive value for identifying MAFLD patients at very high risk of CV disease.

Risk of cancer history in cardiovascular disease among individuals with hypertension.

Hypertension is the leading risk factor for cardiovascular disease (CVD). Although cancer has recently been increasingly recognized as a novel risk factor for CVD events, little is known about whether co-morbid cancer in individuals with hypertension could further increase the risk of CVD events. We sought to determine the association between the cancer history and the risk of CVD in individuals with hypertension. We retrospectively analyzed a large cohort of 747,620 individuals diagnosed with hypertension from January 2005 through May 2022 using the JMDC Claims Database. Composite CVD events, including myocardial infarction (MI), angina pectoris (AP), stroke, heart failure (HF), and atrial fibrillation (AF), were recorded, and a Cox proportional hazard regression was done to estimate hazard ratios (HR) based on the history of cancer and chemotherapy. 26,531 individuals had a history of cancer. During the mean follow-up period of 1269 ± 962 days, 67,154 composite CVD events were recorded. Compared with individuals without a cancer history, cancer survivors had a higher risk of developing composite CVD events (HR: 1.21, 95% confidence interval [CI]: 1.17-1.26). The HRs (95% CIs) associated with cancer history for MI, AP, stroke, HF, and AF were 1.07 (0.90-1.27), 1.13 (1.06-1.20), 1.14 (1.06-1.24), 1.31 (1.25-1.38), and 1.22 (1.10-1.35), respectively. Lastly, individuals who had received chemotherapy for cancer had a particularly higher risk of developing CVD compared to those who did not undergo chemotherapy. A history of cancer was associated with a greater risk of developing CVD among individuals with hypertension.

Cardiovascular Disease Risk in Individuals Following Plant-Based Dietary Patterns Compared to Regular Meat-Eaters.

Plant-based diets (PBDs) have been associated with a lower risk of cardiovascular disease (CVD). The aim was to investigate the predicted 5-year and 10-year risk of developing CVD in individuals following PBDs compared to regular meat-eating diets. This cross-sectional study included n = 240 middle-aged adults habitually consuming dietary patterns for ≥6 months: vegan, lacto-ovo vegetarian (LOV), pesco-vegetarian (PV), semi-vegetarian (SV) or regular meat-eater (RME) (n = 48 per group). Predicted 5-year and 10-year CVD risks were quantified using the Framingham Risk Equation and the Australian Absolute CVD risk calculator, respectively. Multivariable regression analysis was used to adjust for age, sex, smoking status, physical activity, alcohol use and BMI. Over three-quarters of the participants were women, mean age of 53.8 yrs. After adjustments for potential confounders, there was no difference in the predicted risk of CVD between regular-meat diets and PBDs, although crude analyses revealed that vegans had a lower 5-year and 10-year predicted risk of CVD compared to RMEs. SVs, PVs and LOVs had lower CVD risk scores, however, not significantly. Vegans had a favourable cardiometabolic risk profile including significantly lower serum lipid levels, fasting blood glucose and dietary fats and higher dietary fibre intake compared to RMEs. This was the first study to purposefully sample Australians habitually following PBDs. We found that PBDs do not independently influence the predicted risk of CVD, although PBDs tended to have lower risk and vegans had significantly lower cardiometabolic risk factors for CVD.

Cardiovascular Disease Burden in Persons with Mental Illness: Comparison between a U.S. Psychiatry Outpatient Sample and a U.S. General Population Sample

Background. Cardiovascular disease (CVD) and depression are the leading causes of disability in the U.S. Using electronic health record data, we describe the CVD burden among persons with mental illness enrolled in the Penn State Psychiatry Clinical Assessment and Rating Evaluation System (PCARES) Registry between 2015 and 2020. Methods. CVD burden assessment included prevalence of CVD conditions (any major CVD or individual CVD risk factors), indicated medication prescriptions for CVD risk factors, and mean levels of body mass index (BMI, kg/m2), glycosylated hemoglobin (HbA1C, %), glucose (mg/dl), and lipids (mg/dl). We compared the CVD burden between the PCARES sample to a representative sample of adults from the U.S. general population (NHANES 2013-2016) using one-sample chi-square/t-tests for proportions/means. The CVD burden in NHANES participants was adjusted to PCARES age, race, and sex statistics. Results. The PCARES sample (N=3556) had a mean (SE) age of 42.4 (0.3) years and comprised 63.0% women, 85.0% non-Hispanic Caucasians, and 41.0% with major depressive disorder. CVD burden was higher in the PCARES sample compared to NHANES participants for any major CVD (8.6% vs. 4.6%), diabetes (18.4% vs. 10.4%), BMI (30.3 vs. 28.3), HbA1C (6.1 vs. 5.6), cholesterol (185.6 vs. 181.7), triglycerides (153.3 vs. 136.1), and indicated antihypertensive (94.3% vs. 76.9%) and cholesterol-lowering (49.5% vs. 36.7%) medications (Bonferroni-corrected p=0.03 for each outcome). The CVD burden was lower in the PCARES sample compared to NHANES participants for hypertension (45.9% vs. 50.4%), dyslipidemia (43.2% vs. 61.9%), HDL-C (48.4 vs. 41.4), and LDL-C (107.9 vs. 112.0) (Bonferroni-corrected p=0.03 for each outcome). Glucose levels (110.9 vs. 111.9) and indicated antidiabetic medications (87.4% vs. 86.6%) were similar in the two samples (p>0.05). Conclusions. The CVD burden was higher in persons with mental illness compared to the U.S. general population. Integrated mental and physical healthcare services could reduce long-term disability among persons with mental illness.

Relationship Between Social Support and Clinical Outcomes: An Evaluation of Participant-Nominated Treatment Supporters in the HOPE 4 Intervention.

The HOPE 4 trial (Heart Outcomes Prevention and Evaluation 4) investigated the effectiveness of a comprehensive, collaborative model of care, implemented in Colombia and Malaysia, which aimed to reduce cardiovascular disease risk in individuals with hypertension. One component of this intervention was the nomination of a treatment supporter, where participants could select a family member or friend to assist them with their care. The purpose of this study was to investigate the impact of these individuals on participant outcomes, as well as the relationship dynamics between participants and their treatment supporter. Participants in the HOPE 4 intervention group with baseline and 12 months of follow-up were included for analysis. They were divided into Every Visit (n=339) and <Every Visit (n=268) groups based on whether they had a treatment supporter for all 5 or for <5 follow-up visits, respectively. Outcomes were stratified between groups and tested for significance using a generalized linear mixed-effects model. A survey investigating participant satisfaction with their treatment supporter was administered at 12 months. Groups were majority female (53% versus 62%) with a mean age of 63 and 66 years. Country of origin differed between groups (22% versus 86%; Colombia). A 15.5% ([95% CI, 6.2%-24.8%] P=0.004) greater increase in statin medication use was reported in the Every Visit group at 12 months compared with the <Every Visit group. Sixty-one percent versus 48.2% of participants reported high medication adherence at 12 months (P<0.003). The difference in change in systolic blood pressure between groups was not found to be significant at 12 months, though it favored the Every Visit group (-2.3 [95% CI, -6.1 to 1.5]; P=0.045). The majority of survey respondents from either study group strongly agreed that having a treatment supporter positively influenced their health. Long-term support from a nominated treatment supporter was associated with improved adherence, risk factor management, and medication use among individuals with hypertension. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01826019.

Food Environments and Cardiovascular Disease: Evidence From the Health and Retirement Study

IntroductionResidential food environments are one of the important determinants of cardiovascular health. However, past literature has been limited by short-term follow-ups, time-invariant environmental measurements at baseline, and/or not investigating both healthy and unhealthy aspects of the food environment. This study examines the effects of time-varying healthy and unhealthy food environments on incident cardiovascular disease (CVD) over ten years, extracting data from the Health and Retirement Study (2006-2016; N=10,413). MethodsCox proportional hazards modeling was performed with inverse probability weighting to assess the association between time-varying food environmental measures (i.e., densities of grocery stores, supercenters/club stores, full-service restaurants, and fast-food restaurants) and incident CVD over 10 years. Education level and race/ethnicity were tested as potential moderators. Analyses were conducted in 2022-2023. ResultsRace/ethnicity had a significant interaction effect with supercenters/club stores and indicated that a 1-standard-deviation increase in the density of supercenters/club stores was associated with a 6-8% lower risk of incident CVD in non-Hispanic Black (HR=0.78, 95% CI=0.70-0.87) and Hispanic older adults (HR=0.69, 95% CI=0.50-0.96), but not non-Hispanic White older adults. Additionally, education had a significant interaction effect with full-service restaurants, indicating that a 1-standard-deviation increase in the density of full-service restaurants was associated with a 10% lower risk of incident CVD in individuals with 13+ years of schooling, but not those with zero to 12 years of schooling. ConclusionsFindings suggest that public policymakers should be aware of the benefits and nuances of varying food environment components as they can contribute to positive or negative cardiovascular health.

Effect of Statins for Primary Prevention of Cardiovascular Disease According to the Fatty Liver Index.

Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). We investigated the primary preventive effect of statins on CVD according to the level of fatty liver index (FLI), which is a marker of NAFLD. We conducted a nested case-control study on the basis of a nationwide health screening cohort in Korea. The participants were divided into tertiles (T1, T2, and T3) according to their FLI score. Cases were defined as individuals who developed CVD (composite of myocardial infarction and stroke). Three controls were matched to each case and multivariable conditional logistic regression analysis was performed. Within a cohort of 206,263 participants without prior CVD, 7044 individuals suffered the primary outcome. For the nested case-control study, we selected these 7044 cases along with their corresponding 20,641 matched controls. Individuals in the T3 tertiles of FLI had a higher risk of CVD than those in the T1 tertile [adjusted odds ratio (OR) 1.30; 95% confidence interval (CI) 1.20-1.40, P < 0.001]. In sub-analyses based on FLI tertiles, statin therapy was associated with a lower risk of CVD (adjusted OR 0.72; 95% CI 0.61-0.85, P < 0.001) in the T3 tertile but not in the T1 and T2 tertiles. Statin therapy was associated with a reduced risk of CVD in individuals with high FLI but not in those with low FLI. Further research is needed to determine the pathophysiologic mechanism between statin and NAFLD.

Association between atherogenic index of plasma control level and incident cardiovascular disease in middle-aged and elderly Chinese individuals with abnormal glucose metabolism

BackgroundThe atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism.MethodsParticipants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis.Results398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90–1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99–1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01–2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03–2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables.ConclusionsIn middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism.

Low vitamin D levels are linked with increased cardiovascular disease risk in young adults: a sub-study and secondary analyses from the ACTIBATE randomized controlled trial.

Vitamin D deficiency is related to metabolic disturbances. Indeed, a poor vitamin D status has been usually detected in patients with cardiovascular disease (CVD). However, the relationship between vitamin D and CVD risk factors in young adults remains controversial at present. This study aimed to examine the association between circulating 25-hydroxivitamin D (25(OH)D) and CVD risk factors in young adults. The present cross-sectional study included a cohort of 177 young adults aged 18-25years old (65% women). 25(OH)D serum concentrations were assessed using a competitive chemiluminescence immunoassay. Fasting CVD risk factors (i.e., body composition, blood pressure, glucose metabolism, lipid profile, liver, and inflammatory markers) were determined by routine methods. A panel of 63 oxylipins and endocannabinoids (eCBs) was also analyzed by targeted metabolomics. Circulating 25(OH)D concentrations were inversely associated with a wide range of CVD risk factors including anthropometrical (all P ≤ 0.005), body composition (all P ≤ 0.038), glucose metabolism (all P ≤ 0.029), lipid profile (all P < 0.035), liver (all P ≤ 0.011), and pro-inflammatory biomarkers (all P ≤ 0.030). No associations of serum 25(OH)D concentrations were found with pro-inflammatory markers (all P ≥ 0.104), omega-6 and omega-3 oxylipins, nor eCBs concentrations or their analogs (all P ≥ 0.05). The present findings support the idea that 25(OH)D could be a useful predictor of CVD risk in young individuals.

Comparison between general obesity and abdominal adiposity to estimate cardiovascular disease prevalence in individuals with chronic kidney disease: results from NHANES 2005-2016.

Abdominal obesity, regardless of overall obesity, is associated with metabolic abnormalities and with direct impact on cardiovascular risk. The aim of this study was to compare body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) to estimate cardiovascular disease (CVD) prevalence in individuals with chronic kidney disease (CKD). The data analyzed is from 2005-2016 cycles of the NHANES. A total of 2,825 participants with CKD were included in this study, and most of them had a high BMI, 66.1%, to be exact (BMI ≥ 25.0 kg/m² if age <65 or >27.0 if age ≥ 65). The prevalence rates of high WC (≥102 cm for men or ≥88 cm for women) and high WHtR (WHtR>0.5) in the study population were 70.0% and 91.0%, respectively. The results of this study suggest that BMI is a good indicator of the risk of CVDs in individuals with CKD. In addition, the results show that WC and WHtR are associated with CVDs in non-overweight individuals of both sexes. These results indicate that the assessment of abdominal fat is essential even in non-overweight patients because the risk of CVDs cannot be identified in this subpopulation using only BMI.

Recovery From Idiopathic Sudden Sensorineural Hearing Loss: Association With Cardiovascular Disease Risk.

The purpose of this study is to investigate the association between cardiovascular disease (CVD) risk factors and idiopathic sudden sensorineural hearing loss (ISSNHL) disease severity and recovery. A retrospective medical chart review was performed on 90 patients (n = 48 men; Mage = 59.8 years, SD = 15.8) evaluated for ISSNHL. Major CVD risk factors (current tobacco smoking, diabetes, total cholesterol ≥ 240 mg/dl or treatment, and hypertension [systolic blood pressure [BP]/diastolic BP ≥ 140/ ≥ 90 mmHg or treatment]) determined two CVD risk groups: lower (no major risk factors) and higher (one or more risk factors). Two pure-tone averages (PTAs) were computed: PTA0.5,1,2 and PTA3,4,6,8. Complete recovery of ISSNHL was defined as PTAinitial - PTAfollow-up ≥ 10 dB. Logistic regression estimated the odds of ISSNHL recovery by CVD risk status adjusting for age, sex, body mass index, noise exposure, and treatment. Most patients (67.8%) had one or more CVD risk factors. Severity of initial low- and high-frequency hearing loss was similar between CVD risk groups. Recovery was 53.2% for PTA0.5,1,2 and 32.9% for PTA3,4,6,8. With multivariable adjustment, current/former smoking was associated with lower odds of PTA0.5,1,2 recovery (OR = 0.27; 95% CI [0.08, 0.92]). Neither higher CVD risk status nor individual CVD risk factors had a significant association with recovery. For every one-unit increase in Framingham Risk Score, odds of PTA3,4,6,8 recovery were 0.95 times lower (95% CI [0.90, 1.00]) after accounting for age, sex, body mass index, noise exposure, and treatment/time-to-treatment grouping (p = .056). The prognosis of low-frequency ISSNHL recovery is worse among current/former smokers than nonsmokers. Other CVD risk factors and aggregate risk are not significantly related to recovery.

Polycystic Ovarian Syndrome: a Risk Factor for Cardiovascular Disease.

Characterize the risk of cardiovascular disease (CVD) in individuals with polycystic ovarian syndrome (PCOS). Review the pathophysiological pathways that confers CVD risk in individuals with PCOS and interventions to reduce CVD risk. PCOS is a complex syndrome characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries that has metabolic and cardiovascular implications. Intrinsic hormonal dysregulation and chronic low-grade inflammation play an important role in the progression of atherosclerosis in young premenopausal individuals and development of CVD independently of associated traditional risk factors. Management with metformin reduces CVD risk by reducing atherosclerosis progression. PCOS is an important CVD risk factor among individuals of reproductive age. Early detection and interventions are needed to mitigate development of CVD.

Serum uric acid levels and risk of cardiovascular disease in type 2 diabetes: results from a cross-sectional study and Mendelian randomization analysis.

Serum uric acid (SUA) levels have been previously linked to a higher risk of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) according to various observational studies. However, whether this association is causally linked or simply influenced by confounding factors is unclear. Therefore, this study utilized Mendelian randomization (MR) analysis to explore the causality between SUA levels and the risk of CVD in individuals with T2D. Our study cohort consisted of 5723 participants who were diagnosed with T2D in the National Health and Nutrition Examination Survey (NHANES) from 1999-2018. The study assessed the association between SUA levels and the risk of CVD using a multivariable logistic regression model. To further examine causality between SUA levels and CVD, a two-sample MR study was conducted utilizing genetic data from genome-wide association studies (GWAS) involving over 140,000 individuals. The main MR analysis employed the inverse-variance-weighted (IVW) method. Additionally, several sensitivity analyses were performed to evaluate the robustness and pleiotropy of the results. In the cross-sectional study, after multivariable adjustment, participants with SUA levels >6.7 mg/dL exhibited odds ratios (ORs) of 1.51 (95% CI: 1.01-2.26, p=0.049) for heart failure, 1.02 (95% CI: 0.69-1.50, p=0.937) for coronary heart disease, 1.36 (95% CI: 0.78-2.38, p=0.285) for angina, and 1.22 (95% CI: 0.80-1.85, p=0.355) for myocardial infarction when compared to participants with SUA levels ≤ 4.6 mg/dL. However, in the IVW analysis, no causality between SUA levels and the risk of heart failure was observed (OR = 1.03, 95% CI: 0.97-1.09, p = 0.293). The secondary analysis yielded similar results (OR = 1.05, 95% CI: 0.96-1.14, p = 0.299). The sensitivity analyses further supported our primary findings. Based on the MR study, we did not find supporting evidence for a causal association between SUA levels and the risk of heart failure.

Abstract 12485: Cardiovascular Disease Risk, Cognitive Function, and Serum Biomarkers in Older Women Participating in a Lifestyle Intervention

Background: Cardiovascular disease (CVD), including atherosclerotic CVD (ASCVD) and stroke, increase risk of cognitive dysfunction. Serum biomarkers, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1) may be associated with elevated CVD risk and are also emerging as early indicators of cognitive dysfunction. Yet, few studies have investigated associations among all three: CVD risk, cognitive function, and serum biomarkers. Aims: We examined associations between CVD risk, cognitive function, and serum biomarkers in older women with CVD. Methods: Baseline data from an ongoing lifestyle intervention trial for the prevention of cognitive decline in older women with CVD (NCT04556305) were analyzed. Women ( N =253) aged ≥65 years were recruited from ambulatory cardiology clinics. At baseline, CVD risk factors, including blood pressure, body mass index (BMI), waist circumference, and step test (cardiorespiratory fitness) were assessed. ASCVD and CHA 2 DS 2 -VASc scores were calculated to estimate clinical ASCVD and stroke risk, respectively. Serum biomarkers included BDNF, VEGF, and IGF-1. Neurocognitive tests for global cognition, including episodic memory, executive function, semantic memory, and working memory domains, were administered. Linear regression models adjusted for age, education, and race or ethnicity were used to evaluate associations of individual CVD risk factors, ASCVD and CHA 2 DS 2 -VASc scores with cognitive function and serum biomarkers, separately. Results: Of CVD risk factors, waist circumference and BMI were associated with cognition: waist circumference with global cognition, episodic memory, and executive function ( β = -.14 - -.20); BMI with executive function ( β = -.13). ASCVD and CHA2DS2-VASc scores were associated with semantic memory ( β = -.23 and -.16, respectively). Only the ASCVD risk score was associated with BDNF ( β = .18) and VEGF ( β = .24) levels. Conclusion: In older women with CVD, body composition and CVD risk scores appear to be correlated with cognitive function. Future studies should explore associations prospectively and consider serum biomarkers as mediators of the relation of CVD risk to cognitive dysfunction.

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine.

As time has come to translate trial results into individualized medical diagnosis and therapy, we analyzed how to minimize residual risk of cardiovascular disease (CVD) by reviewing papers on "residual cardiovascular disease risk". During this review process we found 989 papers that started off with residual CVD risk after initiating statin therapy, continued with papers on residual CVD risk after initiating therapy to increase high-density lipoprotein-cholesterol (HDL-C), followed by papers on residual CVD risk after initiating therapy to decrease triglyceride (TG) levels. Later on, papers dealing with elevated levels of lipoprotein remnants and lipoprotein(a) [Lp(a)] reported new risk factors of residual CVD risk. And as new risk factors are being discovered and new therapies are being tested, residual CVD risk will be reduced further. As we move from CVD risk reduction to improvement of patient management, a paradigm shift from a reductionistic approach towards a holistic approach is required. To that purpose, a personalized treatment dependent on the individual's CVD risk factors including lipid profile abnormalities should be configured, along the line of P5 medicine for each individual patient, i.e., with Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive approaches.

Accumulated exposure to high non-high-density lipoprotein cholesterol increases the risk of cardiovascular diseases in hypertensive individuals: An 11-year prospective cohort study

ABSTRACT Background The relationship of cumulative non high-density lipoprotein-cholesterol (Cum-non-HDL-C) concentration with the risk of cardiovascular disease (CVD) in individuals with hypertension remains unclear. Methods In total 27 234 participants for whom three consecutive total cholesterol and HDL-C concentrations were available, and who did not have CVD, comprising 13 617 with hypertension and 13 617 without from 2006 to 2010. Participants were placed into four groups according to Cum-non-HDL-C. Cox proportional hazards models were used to evaluate the relationship between Cum-non-HDL-C and the risk of CVD. Results Over a median 11 years, 1,298 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, compared with participants with hypertension and Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios and 95% confidence intervals of CVD associated with Cum-non-HDL-C values of 130–159 mg/dl, 160–189 mg/dl, and ≥ 190 mg/dl were 1.23 (1.01, 1.34), 1.27 (1.04, 1.56), and 1.51 (1.13, 2.01), respectively. Compared with participants without hypertension and a Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios (95% confidence intervals) for the participants with hypertension and Cum-non-HDL-Cs < 130 mg/dl, 130–159 mg/dl, 160–189 mg/dl, and ≥ 190 mg/dl were 1.84 (1.55, 2.18), 2.16 (1.81, 2.59), 2.17 (1.73, 2.70), and 2.45 (1.12, 3.29), respectively. Conclusions A consistently high non-HDL-C concentration increases the risk of CVD in individuals with hypertension, as does prolonged exposure to a high non-HDL-C concentration. Thus, the achievement of target blood pressure and non-HDL-C concentrations should help reduce the risk of CVD in individuals with hypertension.

Association between estimated glomerular filtration rate slope and cardiovascular disease among individuals with and without diabetes: a prospective cohort study

BackgroundPrevious studies have reported an association between a significant decline in estimated glomerular filtration rate (eGFR) over time and an increased risk of cardiovascular disease (CVD). This study aimed to investigate the association between the eGFR slope and CVD among individuals with and without diabetes.MethodsThis prospective cohort study was conducted within the Tehran Lipid and Glucose Study (TLGS) framework. We studied 6919 adults aged 20–70 years, including 985 with diabetes and 5934 without diabetes. The eGFR slope was determined based on repeated measurements of eGFR through linear mixed-effects models. A multivariable Cox proportional hazard model was employed to evaluate the association between eGFR slope, both in continuous and categorical form, and the risk of CVD.ResultsThe slopes of eGFR exhibited a bell-shaped distribution, with a mean (standard deviation (SD)) of -0.63 (0.13) and − 0.70 (0.14) ml/min per 1.73 m2 per year in individuals with and without diabetes, respectively. During a median follow-up of 8.22 years, following the 9-year eGFR slope ascertainment period, a total of 551 CVD events (195 in patients with diabetes) were observed. Among individuals with diabetes, a steeper decline in eGFR slope was significantly associated with a higher risk of CVD events, even after adjusting for baseline eGFR, demographic factors, and traditional risk factors for CVD; slopes of (-1.05 to -0.74) and (-0.60 to -0.52) were associated with 2.12 and %64 higher risks for CVD, respectively, compared with a slope of (-0.51 to 0.16). Among individuals without diabetes, the annual eGFR slope did not show a significant association with the risk of CVD.ConclusionMonitoring the eGFR slope may serve as a potential predictor of CVD risk in individuals with diabetes.

Contribution of intestinal triglyceride-rich lipoproteins to residual atherosclerotic cardiovascular disease risk in individuals with type 2 diabetes on statin therapy

Aims/hypothesisThis study explored the hypothesis that significant abnormalities in the metabolism of intestinally derived lipoproteins are present in individuals with type 2 diabetes on statin therapy. These abnormalities may contribute to residual CVD risk.MethodsTo investigate the kinetics of ApoB-48- and ApoB-100-containing lipoproteins, we performed a secondary analysis of 11 overweight/obese individuals with type 2 diabetes who were treated with lifestyle counselling and on a stable dose of metformin who were from an earlier clinical study, and compared these with 11 control participants frequency-matched for age, BMI and sex. Participants in both groups were on a similar statin regimen during the study. Stable isotope tracers were used to determine the kinetics of the following in response to a standard fat-rich meal: (1) apolipoprotein (Apo)B-48 in chylomicrons and VLDL; (2) ApoB-100 in VLDL, intermediate-density lipoprotein (IDL) and LDL; and (3) triglyceride (TG) in VLDL.ResultsThe fasting lipid profile did not differ significantly between the two groups. Compared with control participants, in individuals with type 2 diabetes, chylomicron TG and ApoB-48 levels exhibited an approximately twofold higher response to the fat-rich meal, and a twofold higher increment was observed in ApoB-48 particles in the VLDL1 and VLDL2 density ranges (all p < 0.05). Again comparing control participants with individuals with type 2 diabetes, in the latter, total ApoB-48 production was 25% higher (556 ± 57 vs 446 ± 57 mg/day; p < 0.001), conversion (fractional transfer rate) of chylomicrons to VLDL was around 40% lower (35 ± 25 vs 82 ± 58 pools/day; p=0.034) and direct clearance of chylomicrons was 5.6-fold higher (5.6 ± 2.2 vs 1.0 ± 1.8 pools/day; p < 0.001). During the postprandial period, ApoB-48 particles accounted for a higher proportion of total VLDL in individuals with type 2 diabetes (44%) compared with control participants (25%), and these ApoB-48 VLDL particles exhibited a fivefold longer residence time in the circulation (p < 0.01). No between-group differences were seen in the kinetics of ApoB-100 and TG in VLDL, or in LDL ApoB-100 production, pool size and clearance rate. As compared with control participants, the IDL ApoB-100 pool in individuals with type 2 diabetes was higher due to increased conversion from VLDL2.Conclusions/interpretationAbnormalities in the metabolism of intestinally derived ApoB-48-containing lipoproteins in individuals with type 2 diabetes on statins may help to explain the residual risk of CVD and may be suitable targets for interventions.Trial registrationClinicalTrials.gov NCT02948777.Graphical

Adherence to a healthy lifestyle, genetic susceptibility to abdominal obesity, cardiometabolic risk markers, and risk of coronary heart disease

BackgroundLittle is known about whether the association between genetic susceptibility to high waist-to-hip ratio (WHR), a measure of abdominal obesity, and incident coronary heart disease (CHD) is modified by adherence to a healthy lifestyle. ObjectivesTo explore the interplay of genetic susceptibility to high WHR and adherence to a healthy lifestyle on incident CHD. MethodsThis study included 282,316 white British individuals from the UK Biobank study. Genetic risk for high WHR was estimated in the form of weighted polygenic risk scores (PRSs), calculated based on 156 single-nucleotide polymorphisms. Lifestyle scores were calculated based on 5 healthy lifestyle factors: regular physical activity, no current smoking, a healthy diet, <3 times/wk of alcohol consumption and 7–9 h/d of sleep. Incident CHD (n = 11,635) was accrued over a median 13.8 y of follow-up, and 12 individual cardiovascular disease risk markers assessed at baseline. ResultsAdhering to a favorable lifestyle (4–5 healthy factors) was associated with a 25% (hazard ratio: 0.75, 95% confidence interval: 0.70, 0.81) lower hazard of CHD compared with an unfavorable lifestyle (0–1 factor), independent of PRS for high WHR. Estimated 12-y absolute risk of CHD was lower for a favorable lifestyle at high genetic risk (1.73%) and medium genetic risk (1.67%) than for an unfavorable lifestyle at low genetic risk (2.08%). Adhering to a favorable lifestyle was associated with healthier levels of cardiovascular disease risk markers (except random glucose and high-density lipoprotein), independent of PRS for high WHR. ConclusionsIndividuals who have high or medium genetic risk of abdominal obesity but adhere to a healthy lifestyle may have a lower risk of developing CHD, compared with those who have low genetic risk and an unhealthy lifestyle. Future clinical trials of lifestyle modification could be implemented for individuals at high genetic risk of abdominal obesity for the primary prevention of CHD events.

Exploring the direct and indirect effects of cardiovascular disease risk factors on exercise blood pressure.

Exaggerated exercise blood pressure (BP) is independently associated with cardiovascular disease (CVD) outcomes. However, it is unknown how individual CVD risk factors may interact with one another to influence exercise BP. The aim of this study was to quantify direct and indirect associations between CVD risk factors and exercise BP, to determine what CVD risk factor/s most-strongly relate to exercise BP. In a cross-sectional design, 660 participants (44 ± 2.6 years, 54% male) from the population-based Childhood Determinants of Adult Health Study had BP measured during low-intensity fixed-workload cycling. CVD risk factors were measured, including body composition, clinic (rest) BP, blood biomarkers, and cardiorespiratory fitness. Associations between CVD risk factors and exercise BP were assessed using linear regression, with direct and indirect pathways of association assessed via structural equation model. Sex, waist-to-hip ratio, fitness, and clinic BP were independently associated with exercise systolic BP (SBP), and along with age, had direct associations with exercise SBP (p < 0.05 all). Most CVD risk factors were indirectly associated with exercise SBP via a relation with clinic BP (p < 0.05 all). Clinic BP, waist-to-hip ratio, and fitness were most-strongly associated (direct and indirect association) with exercise SBP (β[95% CI]: 9.35 [8.04, 10.67], 4.91 [2.56, 7.26], and -2.88 [-4.25, -1.51] mm Hg/SD, respectively). Many CVD risk factors are associated with exercise BP, mostly with indirect effects via clinic BP. Clinic BP, body composition, and fitness were most-strongly associated with exercise BP. These results may elucidate how lifestyle modification could be a primary strategy to decrease exaggerated exercise BP-related CVD risk.