Cardiovascular Disease Risk Markers Research Articles

Non-fasting lipids and cardiovascular disease in those with and without diabetes in Alberta's Tomorrow Project: a prospective cohort study.

Non-fasting remnant cholesterol (RC) is a novel marker of cardiovascular disease (CVD) risk, however data on this relationship in Canadians with diabetes (at high risk of CVD) is lacking. The objective of this analysis was to determine the relationship of RC with CVD in individuals with and without diabetes in the Alberta's Tomorrow Project (ATP) cohort. Non-fasting lipid data collected as part of the ATP was linked to administrative health records (October 2000 - March 2015) to ascertain incident CVD and prevalent diabetes. Participants without prevalent CVD or incident diabetes and who had complete, non-negative non-fasting lipid data collected with triglycerides <4.5mmol/L were included (n=13,631). The relationship between non-fasting RC and incident CVD diagnoses was assessed by Cox proportional hazards regression, after stratification by diabetes status. Participants were 69.8% women with a mean age of 61.6±9.7 years, and 6.5% had prevalent diabetes. Non-fasting RC was higher in participants with diabetes compared to those without (mean 0.94±0.41mmol/L vs. 0.77±0.38mmol/L, p<0.0001) and was associated with increased risk of incident CVD among those without diabetes (adjusted hazard ratio (aHR) 1.22, 95% CI 1.03-1.43, p=0.02). Although a similar trend was observed in participants with diabetes it did not reach statistical significance (aHR 1.31, 95% CI 0.84-2.05, p=0.23). Elevated non-fasting RC predicted increased CVD risk in middle and older-aged adults without diabetes; similar trends were observed in participants with diabetes and requires further testing in a larger sample.

A self-selected 16:8 time-restricted eating quasi-experimental intervention improves various markers of cardiovascular health in middle-age male cyclists

ObjectivesTime-restricted eating (TRE) is a dietary intervention that may offer some protection against cardiovascular disease (CVD), while also preserving performance in athletes. To date however, research on TRE in an active population has only been conducted in college-age cohorts and the effects of TRE in an older, trained population are less understood. Therefore, the aim of this study was to compare the effects of a 4-wk, 16:8 TRE intervention on markers of CVD risk in middle-age, male cyclists. MethodsParticipants (N = 12; age, 51.9 ± 8.6 y; training duration/wk, 375 ± 140 min; peak aerobic capacity, 41.8 ± 5.6 mL/kg/min) reported to the laboratory for two sessions (i.e., at baseline and post-TRE) where blood was drawn from an antecubital vein after an 8-h overnight fast. Dependent variables measured at baseline and post-TRE included insulin, cortisol, brain-derived neurotropic factor, free testosterone, thyroxine, triiodothyronine, C-reactive protein, advanced oxidative protein products, glutathione, tumor necrosis factor (TNF)-α, glucose, and a full lipid profile. ResultsCompared with baseline, TRE significantly lowered TNF-α (12.3 ± 3.4 versus 9.2 ± 2.4 pg/mL; P = 0.02) and glucose concentrations (93.4 ± 9.7 versus 87.5 ± 7.9 mg/dL; P = 0.01), as well as significantly elevated high-density lipoprotein cholesterol levels (45.7 ± 13.7 versus 49.2 ± 12.3 mg/dL; P = 0.04), respectively. No further significant changes were observed between the remaining variables (all P > 0.05). ConclusionOverall, these data suggest that incorporating a 4-wk TRE intervention with habitual endurance training can significantly improve some markers of CVD risk and may compliment the robust health benefits derived from a regular exercise regimen.

Detection of Undiagnosed Elevated Cardiovascular Risk Biomarkers among HIV-Positive Patients on Antiretroviral Therapy (ART) in Kigali-City, Rwanda

Background: Similar to other African countries, life expectancy of people living with HIV infection has improved due to access to antiretroviral therapy (ART) in Rwanda. However, both HIV infection and use of ART are associated with cardiovascular disease (CVD) risks, due to adverse changes in some biomarkers, causing dyslipidemia and other metabolic imbalances. Biomarkers for CVD risk in HIV-infected individuals taking ART, has not been well characterized in Rwanda. We evaluated the association between the use and duration of ART and biomarkers of CVD risk among HIV infected adults in Rwanda. Methods: A total of 150 participants (18-45 years) from HIV clinics in public Health Center in Kigali included n=30 HIV-uninfected (HIV-) and n=120 HIV-infected (HIV+) adults. Among the HIV+ adults, n=40 participants were ART-naïve. Cross-sectional data were collected on healthrelated behaviors and biochemical markers of CVD risk. We compared CVD-related biomarkers between HIV-, HIV+ ART-naïve, and HIV+ on ART groups. Results: The majority of participants were women (60%) and HIV- were younger (35 ± 6 vs. 31 ± 6 years). Total cholesterol and triglycerides concentrations were associated with ART usage. Serum triglycerides concentrations were lower in HIV+ ART-naïve compared to HIV+ on ART (76.6 ± 38.9 mg/dl vs. 85.0 ± 38.3 mg/dl; p&lt; 0.01). While total cholesterol concentrations were higher in HIV+ on ART than HIV+ ART-naïve (136.0 ± 45.1 mg/dl vs. 130.0 ± 36.5 mg/dl; p&lt;0.04), HDL-C was higher in those taking ART (68.7 ± 30.0 mg/dl vs. 55.0 ± 25.7 mg/dl; p=0.02) among HIV+ on ART for 0-6 months and 7-12 months respectively. Conclusion: Elevated levels of cardiovascular risk biomarker profiles (serum total cholesterol and triglycerides) were associated with use of ART in young adults with HIV in the present study. Although these values were within the upper limits of normal, our findings suggest early alterations in biomarkers of cardiovascular risk. These findings underscore the need for early evaluation of lipid profiles as biomarkers of CVD risk, to effectively monitor how ART may contribute to cardiovascular disease and deter treatment programs in Rwanda and other African countries.

Effects of high-intensity interval training on physical morphology, cardiorespiratoryfitness and metabolic risk factors of cardiovascular disease in children and adolescents: A systematic review and meta-analysis.

To systematically evaluate the safety and efficacy of high-intensity interval training in children and adolescents. Eight databases were searched. Descriptive analysis of the efficacy and safety of high-intensity interval training on body shape, cardiorespiratory fitness, and metabolic risk markers of cardiovascular disease in children and adolescents. Subgroup analysis was performed using age, participants, intervention time, and exercise frequency as covariates. 47 studies included 2995 children and adolescents. The results of the meta-analysis showed that high-intensity interval training significantly improved cardiorespiratory fitness indicators (VO2max, SBP, DBP and HRmax) and cardiovascular disease biomarkers (TC and HDL-C). HIIT had no significant effect on body shape indicators (BMI, BF% and WC) or cardiovascular disease biomarkers (TG and LDL-C). Currently, there is insufficient evidence that HIIT with interval running as the predominant form improves physical indicators in children and adolescents. However, HIIT can be promoted in children and adolescents to improve cardiorespiratory fitness and reduce some metabolic risk of cardiovascular disease.

Red blood cell distribution width and all-cause mortality in congestive heart failure patients: a retrospective cohort study based on the Mimic-III database.

The red blood cell distribution width (RDW) is a metric that measures the variation in the size of red blood cells and is presented as the red blood cell volume coefficient of variation. Increased RDW levels are closely linked to an elevated risk of death from congestive heart failure (CHF) and might be a new risk marker for cardiovascular disease. This research sought to evaluate the possible link between RDW levels and all-cause mortality in CHF patients after controlling for other covariates. The publicly accessible Mimic-III database served as the source of data for our research. We employed ICU admission scoring systems to gather information on each patient's demographical data, laboratory test results, comorbid conditions, vital signs, and scores. Among CHF patients, the link between baseline RDW levels and short-, medium-, and long-term all-cause mortality was evaluated by Cox proportional hazard analysis, smooth curve fitting, and Kaplan-Meier survival curves. In total, 4,955 participants were selected for the study with an average age of 72.3 ± 13.5 years (old) and with males accounting for 53.1%. The findings recorded from the fully adjusted Cox proportional hazard model showed that higher RDW was associated with a greater risk of 30-day, 90-day, 365-day, and 4-year all-cause death; the HRs and 95% confidence intervals were 1.11 (1.05, 1.16), 1.09 (1.04, 1.13), 1.10 (1.06, 1.14), and 1.10 (1.06, 1.13), respectively. The results were stable and reliable using subgroup analysis. Smooth curve fitting and the K-M survival curve method further validated our results. The RDW levels had a u-shaped connection with 30-day mortality. The RDW level was linked to an elevated risk of short-, medium-, and long-term all-cause death among CHF patients.

Decreased peripheral vascular function in patients with stage 3 and 4 chronic kidney disease who have elevated symmetric dimethylarginine but not asymmetric dimethylarginine

Cardiovascular disease is a leading cause of death in chronic kidney disease (CKD), yet the mechanisms remain unclear. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous nitric oxide synthase inhibitors shown to be independent risk markers for cardiovascular disease. Previous research has predominantly focused on ADMA as a primary risk marker of reduced vascular function and increased cardiovascular mortality in end-stage (stage 5) CKD. However, limited research has explored the potential roles of ADMA and SDMA in relation to vascular function in the middle stages (stages 3 and 4) of CKD. Therefore, we tested the hypothesis that patients with stage 3-4 CKD would have elevated circulating ADMA and SDMA, which would correspond to a reduced vascular function compared to controls. We studied 17 patients with stage 3-4 CKD (age: 66 ± 7 years, 5 males, eGFR: 44 ± 16 ml/min/1.73m 2 ) and 8 controls (age: 59 ± 7 years; 3 males, eGFR: 81 ± 14 ml/min/1.73m 2 ). ADMA and SDMA were assessed in whole blood serum using liquid chromatography/tandem mass spectrometry by a commercial laboratory (Quest diagnostics). Macro- and micro-vascular function were assessed as brachial artery flow-mediated dilation (FMD; %) and peak reactive hyperemia blood velocity, respectively, using duplex Doppler ultrasound. Arterial stiffness was assessed as carotid-femoral pulse wave velocity (cfPWV) using arterial tonometry. Data are expressed as mean ± standard deviation. Interestingly, we found that SDMA (control: 103 ± 14, CKD: 143 ± 42 ng/mL, p=0.01) but not ADMA (control: 109 ± 7; CKD: 111 ± 28 ng/mL, p=0.40) was significantly elevated in patients with CKD compared to controls. FMD was significantly reduced in the CKD group (control: 5.04 ± 2.59.; CKD: 3.18 ± 1.98 %, p=0.03), while peak blood velocity was similar between groups (control: 53.47 ± 10.40, CKD: 59.72 ± 23.99 cm/s, p=0.25). There tended to be a negative relationship between SDMA concentrations and FMD (R= -0.31, p=0.07), whereas there was no relationship between ADMA and FMD (R= 0.22, p=0.14). Arterial stiffness was also significantly greater in the patient with CKD compared to controls (control: 6.74 ± 0.91, CKD: 7.95 ± 1.60 m/s, p=0.034). These data suggest that patients with stage 3-4 CKD who have elevated circulating SDMA but not ADMA exhibit an impaired macro-vascular function. Moreover, an augmented cfPWV also suggests increased arterial stiffness in patients with CKD with elevated SDMA. Collectively, these preliminary findings suggest that SDMA, but not ADMA, may play a more predominant role in mediating impaired vascular function in the middle stages of CKD. This project was supported by the National Heart, Lung, and Blood Institute R01 HL-127071. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

B-vitamin Treatment Modifies the Mortality Risk Associated with Calcium Channel Blockers in Patients with Suspected Stable Angina Pectoris: A Prospective Cohort Study

BackgroundCalcium channel blockers (CCBs) are used for the treatment of cardiovascular disease (CVD), including angina pectoris, and hypertension; however, the effect on survival remains uncertain. CCBs impair fibrinolysis and have been linked to elevated plasma homocysteine (Hcy), a CVD risk marker. ObjectiveWe explored the association between CCB use and mortality in a large prospective cohort of patients with suspected stable angina pectoris (SAP), and potential effect modifications by Hcy-lowering B-vitamin treatment (folic acid, B12, and/or B6) as 61.8% of the patients participated in a randomized placebo-controlled B-vitamin intervention trial. MethodsPatient baseline continuous characteristics according to CCB treatment were tested by linear regression. Hazard ratios (HRs) for mortality associated with CCB treatment, also according to B-vitamin intervention, were examined using Cox regression analysis. The multivariable model included CVD risk factors, medical histories, and the use of CVD medications. ResultsA total of 3991 patients (71.5 % men) were included, of whom 907 were prescribed CCBs at discharge. During 10.3 years of median follow-up, 20.6% died and 8.9% from cardiovascular- and 11.7% from non-cardiovascular causes. Patients treated with CCBs had higher plasma Hcy, fibrinogen levels, and erythrocyte sedimentation rate (all P<0.001). Furthermore, CCB use was positively associated with mortality, also after multivariable adjustments (HRs [95% CIs]: 1.34 [1.15,1.57], 1.35 [1.08,1.70], and 1.33 [1.09,1.64] for total, CVD, and non-CVD death, respectively). Numerically stronger associations were observed among patients not treated with B-vitamins (HR [95% CI]: 1.54 [1.25, 1.88], 1.69 [1.25, 2.30], and 1.41 [1.06, 1.86] for total, CVD deaths, and non-CVD deaths, respectively), whereas no association was seen in patients treated with B-vitamins (HR [95% CI]: 1.15 [0.91, 1.46], 1.09 [0.76, 1.57], and 1.20 [0.88, 1.65]). ConclusionsIn patients with suspected SAP, CCB treatment was associated with increased mortality risk primarily among patients not treated with B-vitamins.

Astaxanthin, a natural antioxidant, lowers cholesterol and markers of cardiovascular risk in individuals with prediabetes and dyslipidaemia.

To determine the effects of astaxanthin treatment on lipids, cardiovascular disease (CVD) markers, glucose tolerance, insulin action and inflammation in individuals with prediabetes and dyslipidaemia. Adult participants with dyslipidaemia and prediabetes (n = 34) underwent baseline blood draw, an oral glucose tolerance test and a one-step hyperinsulinaemic-euglycaemic clamp. They were then randomized (n = 22 treated, 12 placebo) to receive astaxanthin 12 mg daily or placebo for 24 weeks. Baseline studies were repeated after 12 and 24 weeks of therapy. After 24 weeks, astaxanthin treatment significantly decreased low-density lipoprotein (-0.33 ± 0.11 mM) and total cholesterol (-0.30 ± 0.14 mM) (both P < .05). Astaxanthin also reduced levels of the CVD risk markers fibrinogen (-473 ± 210 ng/mL), L-selectin (-0.08 ± 0.03 ng/mL) and fetuin-A (-10.3 ± 3.6 ng/mL) (all P < .05). While the effects of astaxanthin treatment did not reach statistical significance, there were trends toward improvements in the primary outcome measure, insulin-stimulated, whole-body glucose disposal (+0.52 ± 0.37 mg/m2 /min, P = .078), as well as fasting [insulin] (-5.6 ± 8.4 pM, P = .097) and HOMA2-IR (-0.31 ± 0.16, P = .060), suggesting improved insulin action. No consistent significant differences from baseline were observed for any of these outcomes in the placebo group. Astaxanthin was safe and well tolerated with no clinically significant adverse events. Although the primary endpoint did not meet the prespecified significance level, these data suggest that astaxanthin is a safe over-the-counter supplement that improves lipid profiles and markers of CVD risk in individuals with prediabetes and dyslipidaemia.

Bempedoic acid lowers high-sensitivity C-reactive protein and low-density lipoprotein cholesterol: Analysis of pooled data from four phase 3 clinical trials

Background and aimsHigh-sensitivity C-reactive protein (hsCRP), a marker for atherosclerotic cardiovascular disease risk, is reduced by bempedoic acid. We assessed the relationship between changes in low-density lipoprotein cholesterol (LDL-C) and hsCRP in relation to baseline statin use. MethodsPooled data from four phase 3 trials (patients on maximally tolerated statins [Pool 1] and patients receiving no or low-dose statins [Pool 2]) were used to determine the proportion of patients with baseline hsCRP ≥2 mg/L who achieved hsCRP <2 mg/L at week 12. The percentage of patients who achieved hsCRP <2 mg/L and guideline-recommended LDL-C (Pool 1, <70 mg/dL; Pool 2, <100 mg/dL) was determined for patients on statins in Pool 1 and those not on statins in Pool 2, as was the correlation between percent changes in hsCRP and LDL-C. ResultsOverall, 38.7% in Pool 1 and 40.7% in Pool 2 with baseline hsCRP ≥2 mg/L achieved hsCRP <2 mg/L with bempedoic acid, with little effect from background statin. Among patients taking a statin in Pool 1 or not taking a statin in Pool 2, 68.6% and 62.4% achieved hsCRP <2 mg/L. Both hsCRP <2 mg/L and United States guideline–recommended LDL-C were achieved more often with bempedoic acid vs. placebo (20.8% vs. 4.3%, respectively, in Pool 1 and 32.0% vs. 5.3%, in Pool 2). Changes in hsCRP and LDL-C were only weakly correlated (Pool 1, r = 0.112; Pool 2, r = 0.173). ConclusionsBempedoic acid significantly reduced hsCRP irrespective of background statin therapy; the effect was largely independent of LDL-C lowering.

Relationship between combat-related traumatic injury and ultrashort term heart rate variability in a UK military cohort: findings from the ADVANCE study

IntroductionCombat-related traumatic injury (CRTI) has been linked to an increased cardiovascular disease (CVD) risk. The long-term impact of CRTI on heart rate variability (HRV)—a robust CVD risk marker—has not been...

Metformin Monotherapy Alters the Human Plasma Lipidome Independent of Clinical Markers of Glycemic Control and Cardiovascular Disease Risk in a Type 2 Diabetes Clinical Cohort.

Type 2 diabetes (T2D) is a rising pandemic worldwide. Diet and lifestyle changes are typically the first intervention for T2D. When this intervention fails, the biguanide, metformin, is the most common pharmaceutical therapy. Yet, it's full mechanisms of action remain unknown. In this work, we applied an ultrahigh resolution, mass spectrometry-based platform for untargeted plasma metabolomics to human plasma samples from a case-control observational study of non-diabetic and well-controlled T2D subjects, the latter treated conservatively with metformin or diet and lifestyle changes only. No statistically significant differences existed in baseline demographic parameters, glucose control, or clinical markers of cardiovascular disease risk between the two T2D groups, which we hypothesized would allow the identification of circulating metabolites independently associated with treatment modality. Over 3000 blank-reduced metabolic features were detected, with the majority of annotated features being lipids or lipid-like molecules. Altered abundance of multiple fatty acids and phospholipids were found in T2D subjects treated with diet and lifestyle changes as compared to non-diabetic subjects: changes that were often reversed by metformin. Our findings provide direct evidence that metformin monotherapy alters the human plasma lipidome independent of T2D disease control and support a potential cardioprotective effect of metformin worthy of future study. Significance Statement This work provides important new information on the systemic effects of metformin in type 2 diabetic subjects. We observed significant changes in the plasma lipidome with metformin therapy, with metabolite classes previously associated with cardiovascular disease risk significantly reduced as compared to diet and lifestyle changes. While cardiovascular disease risk was not a primary outcome of our study, our results provide a jumping-off point for future work into the cardioprotective effects of metformin, even in well-controlled type 2 diabetes.

The Triglyceride/High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio as a Risk Marker for Metabolic Syndrome and Cardiovascular Disease.

Atherosclerosis is an immunoinflammatory pathological procedure in which lipid plaques are formed in the vessel walls, partially or completely occluding the lumen, and is accountable for atherosclerotic cardiovascular disease (ASCVD). ACSVD consists of three components: coronary artery disease (CAD), peripheral vascular disease (PAD) and cerebrovascular disease (CCVD). A disturbed lipid metabolism and the subsequent dyslipidemia significantly contribute to the formation of plaques, with low-density lipoprotein cholesterol (LDL-C) being the main responsible factor. Nonetheless, even when LDL-C is well regulated, mainly with statin therapy, a residual risk for CVD still occurs, and it is attributable to the disturbances of other lipid components, namely triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Increased plasma TG and decreased HDL-C levels have been associated with metabolic syndrome (MetS) and CVD, and their ratio, TG/HDL-C, has been proposed as a novel biomarker for predicting the risk of both clinical entities. Under these terms, this review will present and discuss the current scientific and clinical data linking the TG/HDL-C ratio with the presence of MetS and CVD, including CAD, PAD and CCVD, in an effort to prove the value of the TG/HDL-C ratio as a valuable predictor for each aspect of CVD.

Population-representative study reveals cardiovascular and metabolic disease biomarkers associated with misaligned sleep schedules.

Social jetlag manifests as a difference in sleep timing on workdays and free days. Social jetlag is often associated with shorter, lower-quality sleep, so it is unclear how much the chronic circadian misalignment contributes to observed negative health outcomes. We aimed to (1) investigate associations between social jetlag, chronotype (one of its determinants), and the levels of health markers, (2) describe factors associated with social jetlag, and (3) examine whether working from home can reduce social jetlag. Adult respondents participated in a nationally representative longitudinal survey of Czech households (individuals in each wave: n2018/19/20 = 5132/1957/1533), which included Munich ChronoType Questionnaire to evaluate chronotype and social jetlag. A subset provided blood samples (n2019 = 1957) for detection of nine biomarkers and was surveyed in three successive years (social jetlag calculated for n2018/19/20 = 3930/1601/1237). Data were analyzed by nonparametric univariate tests and mixed effects multivariate regression with social jetlag, chronotype, sex, age, body-mass index, and reported diseases as predictors and biomarker levels as outcomes. Higher social jetlag (≥0.65 h) was significantly associated with increased levels of total cholesterol and low-density lipoprotein cholesterol, particularly in participants older than 50 years (Mann-Whitney, men: pCHL = 0.0005, pLDL = 0.0009; women: pCHL = 0.0079, pLDL = 0.0068). Extreme chronotypes were associated with cardiovascular disease risk markers regardless of social jetlag (Kruskal-Wallis, p < 0.0001). Commuting to work and time stress were identified as important contributors to social jetlag. Individual longitudinal data showed that working from home decreased social jetlag and prolonged sleep. We report significant associations between sleep phase preference, social jetlag, and cardio-metabolic biomarkers.

The Effect of a Vegan Diet on the Cardiovascular System

The vegan diet, often known as a plant-rich diet, consists primarily of plant-based meals. This dietary approach may be beneficial to one's health and the environment and is valuable to the immune system. Plants provide vitamins, minerals, phytochemicals, and antioxidants, components that promote cell survival and immune function, allowing its defensive mechanisms to work effectively. The term "vegan diet" comprises a range of eating patterns that prioritize nutrient-rich foods such as fruits and vegetables, legumes, whole grains, nuts, and seeds. In comparison to omnivorous diets, which are often lower in such products, the vegan diet has been favorably connected with changes in cardiovascular disease (CVD) risk markers such as reduced body mass index (BMI) values, total serum cholesterol, serum glucose, inflammation, and blood pressure. Reduced intake of low-density lipoprotein (LDL), saturated fat, processed meat, and greater consumption of fiber and phytonutrients may improve cardiovascular health. However, vegans have much smaller amounts of nutrients such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), selenium, zinc, iodine, and vitamin B12, compared to non-vegans, which may lead to detrimental cardiovascular effects. This review aims to present the effect of plant-based diets (PBDs), specifically vegan diets, on the cardiovascular system.

Pregnancy loss and risk of incident CVD within 5 years: Findings from the Women's Health Initiative.

Previous studies have demonstrated an increased risk of cardiovascular disease (CVD) in women with a history of pregnancy loss. Less is known about whether pregnancy loss is associated with age at the onset of CVD, but this is a question of interest, as a demonstrated association of pregnancy loss with early-onset CVD may provide clues to the biological basis of the association, as well as having implications for clinical care. We conducted an age-stratified analysis of pregnancy loss history and incident CVD in a large cohort of postmenopausal women aged 50-79 years old. Associations between a history of pregnancy loss and incident CVD were examined among participants in the Women's Health Initiative Observational Study. Exposures were any history of pregnancy loss (miscarriage and/or stillbirth), recurrent (2+) loss, and a history of stillbirth. Logistic regression analyses were used to examine associations between pregnancy loss and incident CVD within 5 years of study entry in three age strata (50-59, 69-69, and 70-79). Outcomes of interest were total CVD, coronary heart disease (CHD), congestive heart failure, and stroke. To assess the risk of early onset CVD, Cox proportional hazard regression was used to examine incident CVD before the age of 60 in a subset of subjects aged 50-59 at study entry. After adjustment for cardiovascular risk factors, a history of stillbirth was associated with an elevated risk of all cardiovascular outcomes in the study cohort within 5 years of study entry. Interactions between age and pregnancy loss exposures were not significant for any cardiovascular outcome; however, age-stratified analyses demonstrated an association between a history of stillbirth and risk of incident CVD within 5 years in all age groups, with the highest point estimate seen in women aged 50-59 (OR 1.99; 95% CI, 1.16-3.43). Additionally, stillbirth was associated with incident CHD among women aged 50-59 (OR 3.12; 95% CI, 1.33-7.29) and 60-69 (OR 2.06; 95% CI, 1.24-3.43) and with incident heart failure and stroke among women aged 70-79. Among women aged 50-59 with a history of stillbirth, a non-significantly elevated hazard ratio was observed for heart failure before the age of 60 (HR 2.93, 95% CI, 0.96-6.64). History of stillbirth was strongly associated with a risk of cardiovascular outcomes within 5 years of baseline in a cohort of postmenopausal women aged 50-79. History of pregnancy loss, and of stillbirth in particular, might be a clinically useful marker of cardiovascular disease risk in women.

Allostatic load and cardiovascular outcomes in males with prostate cancer.

Cardiovascular disease (CVD) is the leading cause of death in men with prostate cancer (PC). Accumulated stress plays an important role in CVD development. The cumulative burden of chronic stress and life events can be measured using allostatic load (AL). The initial cohort included males aged 18 years and older diagnosed with PC (2005-2019). AL was modeled as an ordinal variable (0-11). Fine-Gray competing risk regressions measured the impact of precancer diagnosis AL and postdiagnosis AL in 2-year major cardiac events (MACE). The effect of AL changes over time on MACE development was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after PC diagnosis). We included 5261 PC patients of which 6.6% had a 2-year MACE. For every 1-point increase in AL before and within 60 days after PC diagnosis, the risk of MACE increased 25% (adjusted hazard ratio [aHR] =1.25, 95% confidence interval [CI] = 1.18 to 1.33) and 27% (aHR = 1.27, 95% CI = 1.20 to 1.35), respectively. Using AL as a time-varying exposure, the risk of MACE increased 19% (aHR = 1.19, 95% CI = 1.11 to 1.27), 22% (aHR = 1.22, 95% CI = 1.14 to 1.33), 28% (aHR = 1.28, 95% CI = 1.23 to 1.33), and 31% (aHR = 1.31, 95% CI = 1.27 to 1.35) for every 1-point increase in AL before, 2 months after, 6 months after, and 1 year after PC diagnosis, respectively. AL and its changes over time are associated with MACE in PC patients, suggesting a role of a biological measure of stress as a marker of CVD risk among men with PC.

Association of circulating MtDNA with CVD in hemodialysis patients and in vitro effect of exogenous MtDNA on cardiac microvascular inflammation

BackgroundChronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.MethodsForty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and erythrocyte sedimentation rate (ESR) were measured by standard assays. Ten-year CVD risk was calculated from the Framingham risk score (FRS) model. In vitro study, human cardiac microvascular endothelial cells (HCMECs) were incubated with normal or uremic serum, with or without exogenous MtDNA. Intracellular toll-like receptor 9 (TLR9), adhesion molecule 1 (ICAM-1), MCP-1 and tumor necrosis factor-α (TNF-α) and cytosolic MtDNA were detected by qPCR.ResultsPlasma MtDNA in MHD patients was significantly higher than healthy controls (4.74 vs. 2.41 × 105 copies/mL; p = 0.000). Subsequently, the MHD patients were classified into two groups based on the MtDNA median (4.34 × 105 copies/mL). In stratified analyses, the levels of Hs-CRP (5.02 vs. 3.73 mg/L; p = 0.042) and MCP-l (99.97 vs. 64.72 pg/mL; p = 0.008) and FRS (21.80 vs. 16.52; p = 0.016) in the high plasma MtDNA group were higher than those in the low plasma MtDNA group. In vitro study, we found that exogenous MtDNA aggravated uremic serum-induced microvascular inflammation (ICAM-1 and TNF-α) in HCMECs (all p < 0.05). Besides, the addition of MtDNA to the medium resulted in a further increase in cytosolic MtDNA and TLR9 levels in uremic serum-treated cells (all p < 0.05). In patients with MHD, MtDNA levels in plasma were significantly reduced after a single routine hemodialysis (pre 4.47 vs. post 3.45 × 105 copies/mL; p = 0.001) or hemodiafiltration (pre 4.85 vs. post 4.09 × 105 copies/mL; p = 0.001). These two approaches seem similar in terms of MtDNA clearance rate (21.26% vs. 11.94%; p = 0.172).ConclusionsOverall, the present study suggests that MtDNA released into the circulation under the uremic toxin environment may adversely affect the cardiovascular system by exacerbating microvascular inflammation, and that reducing circulating MtDNA might be a future therapeutic strategy for the prevention of MHD-related CVD.

Creatine kinase is associated with glycated haemoglobin in a nondiabetic population. The Tromsø study.

Creatine kinase (CK) has been associated with insulin resistance and identified as a risk marker of cardiovascular disease largely by its relationship with hypertension and increased body mass index. This study determined whether CK is a predictor of glycated haemoglobin (HbA1C) in a nondiabetic general population. Associations between CK and the outcome variable HbA1C (%) were performed by variance and multivariate analyses in 11662 nondiabetic subjects defined as HbA1C (%) <6.5 who participated in the population based Tromsø study (Tromsø 6) in Norway. Abnormal elevated CK was detected in 543/11662 participants (4.66%). Mean HbA1C (%) in the "high CK" group was 5.62 (SD = 0.33) compared to 5.52 (SD = 0.36) in the "normal CK" group, P <0.001. CK increased significantly and linearly with higher levels of HbA1C (%) quartiles in women (P <0.001) and non-linearly in men (P <0.001). In a multivariate analysis, CK was independently associated with HbA1C (%) after adjusting for age, sex, body mass index, blood pressure, glucose, lipids, C-reactive protein, creatinine, alanine transaminase and aspartate aminotransferase. A 1-unit increase in log CK was associated with a 0.17-unit increase in HbA1C (%). These data demonstrate a positive and independent association between CK and glycated haemoglobin in a nondiabetic general population.

Sex-specific associations of reservoir-excess pressure parameters with age and subclinical vascular remodeling.

Central artery reservoir pressure and excess pressure (XSP) are associated with cardiovascular disease (CVD) events and mortality. However, sex differences in the trajectory of central reservoir pressure and XSP with advancing age and their relations with vascular markers of subclinical CVD risk are incompletely understood. Therefore, we tested the hypothesis that central reservoir pressure and XSP would be positively associated with advancing age and vascular markers of subclinical CVD risk in men and women. Healthy adults ( n = 398; aged 18-80 years, 60% female individuals) had central (carotid) artery pressure waveforms acquired by applanation tonometry. Reservoir pressure and XSP peaks and integrals were derived retrospectively from carotid pressure waveforms using custom written software. Carotid artery intimal-medial thickness (IMT) was measured by ultrasonography, and aortic stiffness was determined from carotid-femoral pulse wave velocity (cfPWV). Reservoir pressure peak, reservoir pressure integral and XSP integral were higher with age in both men and women ( P < 0.05), whereas XSP peak was lower with age in men ( P < 0.05). In women, both reservoir pressure peak ( β = 0.231, P < 0.01) and reservoir pressure integral ( β = 0.254, P < 0.01) were associated with carotid artery IMT, and reservoir pressure peak was associated with cfPWV ( β = 0.120, P = 0.02) after adjusting for CVD risk factors. Central artery reservoir pressure and XSP were higher with advancing age in men and women, and reservoir pressure peak was associated with both carotid artery wall thickness and aortic stiffness in women but not men. Central reservoir pressure peak may provide some insight into sex differences in vascular remodeling and subclinical CVD risk with advancing age in healthy adults.

Effect of abdominal aortic calcification on the prognosis and recurrence of colorectal cancer stages II–III: A retrospective cohort study

Abdominal aortic calcification (AAC) is a well-known risk marker for cardiovascular disease. However, its clinical effect on patients who underwent radical surgery for colorectal cancer (CRC) stages II-III is unclear. This study aimed to analyze the associations between AAC and prognosis of patients with stage II-III CRC. To evaluate the effect of AAC on clinical outcomes, prognosis, and metastatic patterns of CRC, we analyzed 362 patients who underwent radical surgery for stage II-III CRC between 2010 and 2018. The high AAC group had significantly worse overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In the multivariate Cox regression analyses, a high AAC was an independent risk factor for poor OS (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.23-4.59; p = 0.01), poor CSS (HR, 5.22; 95% CI, 1.74-15.6; p < 0.01), and poor RFS (HR, 1.83; 95% CI, 1.19-2.83; p < 0.01). A high AAC was not associated with a risk of lung metastasis or local or peritoneal recurrence, but a risk for liver metastasis of CRC. A high AAC showed a strong relationship with poor OS, CSS, and RFS after curative resection for stage II-III CRC. A high AAC was also associated with a risk for liver metastasis, which may worsen the prognosis in stage II-III CRC. AAC could be a new clinical tool for predicting the prognosis for patients in stage II-III CRC.