Cardiovascular Disease Risk Markers Research Articles

Cross-sectional analysis of non-HDL/HDL cholesterol ratio as a marker for cardiovascular disease risk in middle-aged and older adults: Evidence from the CHARLS study

While cardiovascular disease is linked to abnormal lipid metabolism, the relationship between NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio), a new lipid metric, and cardiovascular disease in middle-aged and older adults in China is still unclear. This cohort study, based on a population sample, examined the incidence of cardiovascular disease (CVD) events, including stroke and heart disease. It utilized self-reported diagnoses from the study's inception and during Wave 4, involving 9259 participants from the China Health and Retirement Longitudinal Study (CHARLS). The research employed restricted cubic spline models and multivariate logistic regression to investigate possible non-linear relationships. Additionally, subgroup analyses were conducted to assess the influence of socio-demographic factors on the outcomes. During the seven-year follow-up period, 1,139 participants developed CVD, including 742 cases of heart problems and 582 strokes. In Model 3, it was observed that for each unit increase in the highest NHHR group, the risk of developing CVD increased by 98%, the risk of stroke increased by 48%, and the risk of heart problems increased by 115%. Subgroup analyses indicated that this correlation was more pronounced among individuals under 60 years of age and those with hypertension. According to the current study, elevated NHHR ratio is an important risk factor for CVD in middle-aged and elderly Chinese. Early intervention in patients with higher NHHR ratios may help to further reduce the incidence of CVD.

Impact of white matter hyperintensity volume on cognition among US Mexican American adults.

Higher white matter hyperintensity (WMH) volume is a marker of cardiovascular disease (CVD) risk. CVD risk factors increase risk for Alzheimer's disease and related dementias (ADRD). Mexican Americans (MA) and individuals of other Hispanic/Latino heritages have higher risk for CVD and ADRD. However, knowledge of associations between WMH volume and cognition in these groups remains limited. We conducted a cross-sectional study of associations between WMH volume and neuropsychological performance (attention/executive functioning, memory) in MA (n = 851) and non-Hispanic White (NHW; n = 747) adults in the Health and Aging Brain Study: Health Disparities. The MA group (mean age = 63.72 ± 7.90 years; 66.3% female) had higher rates of consensus diagnoses of hypertension and diabetes, whereas the NHW group (mean age = 69.18 ± 8.65 years; 55.2% female) had higher rates of diagnosed CVD (ps < .01). WMH volumes were higher among individuals with CVD risk factors/conditions (ps < .01). There were differential associations between WMH and neuropsychological performance across ethnoracial groups (ps < .001), wherein associations were steeper in the NHW group than in the MA group. Lower educational level was associated with higher WMH volume in the NHW group (p < .001), but no association was seen in the MA group (p > .05). Negative effects of pathological changes in the form of WMH on cognition may be less robust or consistent for MA adults than NHW adults. Furthermore, the impact of WMH on cognition in NHW adults may be mitigated by cognitive reserve related to educational attainment.

Can Cardiovascular Risk Be Simply Estimated in Nonalcoholic Fatty Liver Disease Patients?

Backgrounds and Aims: In the pathogenesis of nonalcoholic fatty liver disease (NAFLD), inflammation plays a pivotal role. The presence of inflammatory cells is closely linked with epicardial adipose tissue (EAT). A recently identified prognostic indicator for cardiovascular disease (CVD) is the ratio of monocyte count to HDL-cholesterol (MHR). Our primary aim was to investigate the relationship between EAT and markers of inflammation in individuals with NAFLD, and to evaluate its predictability using straightforward diagnostic measures. Material-Method: This retrospective study included two hundred eighteen patients who underwent thoracic computed tomography angiography between 2014 and 2021. The patients were divided into the NAFLD group (HU48 IU) according to the liver attenuation ratio. 136 patients in the NAFLD group and 82 in the non-NAFLD group. Results: The body mass index (BMI), triglyceride levels, notably the EAT volume and MHR in the NAFLD group, exhibited higher values than non-NAFLD group. Among participants in the NAFLD group, a positive correlation was observed between EAT volume and factors such as age, MHR, c-reactive protein, BMI, urea, glucose, and alanine aminotransferase. Through linear regression analysis, it was determined that MHR stood as the sole independent predictor of EAT volume in patients with NAFLD. Conclusion: EAT volume, a risk marker for CVD, can be predicted in NAFLD patients by MHR without radiological methods. Thus, easier and earlier detection of NAFLD patients in the high-risk group for CVD will be possible.

Serum Levels of Trace Elements (Magnesium, Iron, Zinc, Selenium, and Strontium) are Differentially Associated with Surrogate Markers of Cardiovascular Disease Risk in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD), which is attributed to inflammatory processes that accelerate atherosclerosis. Therefore, the exploration of novel biomarkers association is needed. This study investigated the associations between serum trace elements (Fe, Zn, Mg, Se, and Sr) and surrogate markers of CVD in 219 RA patients and compared them with those with metabolic disorders (MetD, n = 82) and control participants (n = 64). Surrogate markers included carotid intima-media thickness (cIMT), carotid plaque presence (cPP), pulse wave velocity (PWV), distensibility (DIST), and the augmentation index (AIx). RA patients displayed heightened inflammatory markers, increased arterial stiffness and thickness, and elevated CV risk factors. Compared with those in control participants, Se levels in RA patients were lower, regardless of sex. Women and men with RA had lower Sr and Mg levels than those with MetD, respectively. Backward regression models demonstrated inverse associations of Sr and Zn with cIMT in men with RA and those with MetD, respectively. In RA patients, Sr and Zn were predictors of an increased AIx, with sex-specific associations. Increased Fe levels were associated with an increased AIx in women with MetD. Fe and Zn were predictors of increased cIMT in control participants, with sex-specific associations. Serum trace elements are independently associated with surrogate markers of CVD in patients with RA, highlighting their potential role in CV risk assessment. Prospective studies are essential for validating these associations and establishing optimal trace element levels for managing CVD risk in patients with RA.

Investigating lifestyle determinants of carotid intima-media thickness: cross-sectional insights from the UK biobank cohort

Abstract Background/Introduction Carotid intima-media thickness (CIMT) is recognised as a crucial marker for cardiovascular disease (CVD) risk, inherently associated with vascular ageing and influenced by biomarkers such as elevated levels of HbA1c, dyslipidaemia, and hypertension. The significance of CIMT lies in its potential to act as a surrogate marker for CVD risk, bridging a gap in understanding the progression of vascular health. Purpose This study aims to investigate the correlation between CIMT and a composite biomarker score to enhance risk assessment and guide the prevention and treatment strategies for CVD. By examining this relationship, the study seeks to underline the importance of CIMT progression as an indicative marker for cardiovascular health. Methods A subset of participants from the UK Biobank, with valid CIMT measurements taken in 2014, was selected for this analysis. CIMT was measured through ultrasound techniques and considered the primary outcome variable, treated as continuous in the analysis. A linear regression model was used to examine the correlation between CIMT and lifestyle risk factors, with a focus on the moderating effects of sex. Results The study included 29,292 UK Biobank participants (48% female, mean age 64 years), with a mean CIMT of 687.11µm (SD 124.28). Significant predictors of CIMT were age (β=6.05) and male gender (β=13.02). Lifestyle factors such as body weight (β=0.84) and high physical activity (β=10.66) were positively correlated with CIMT. Current smokers showed a stronger association with CIMT (β=14.47) compared to former smokers (β=9.21). In females, age (β=6.07), body weight (β=0.71), CRBI score (β=9.95), and previous smoking (β=6.64) positively correlated with CIMT, while high CRP levels were negatively associated (β=-0.61). In males, significant factors included age (β=6.04), body weight (β=0.95), CRBI score (β=10.79), and smoking history, with previous smokers showing a stronger effect (β=11.67) and high physical activity notably associated with increased CIMT (β=18.73). Conclusion(s) The study's findings highlight the impact of lifestyle choices on vascular health, demonstrating that active living, maintaining a healthy weight, and abstaining from smoking can positively affect CIMT and thereby reduce CVD risk. The results confirm the importance of weight management for arterial health across all demographics and highlight the role of abnormal biomarker levels in increasing CIMT. This study contributes to a deeper understanding of the factors affecting CIMT and, by extension, cardiovascular health, advocating for targeted lifestyle interventions to mitigate CVD risk.

Lipoprotein(a) and atherosclerotic cardiovascular disease in a Brazilian tertiary hospital population

Abstract Background/Introduction Elevated levels of lipoprotein(a) [Lp(a)] are a strong risk marker of atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction (MI), ischemic stroke, and peripheral arterial disease, as well as of aortic valve calcification and stenosis. However, few studies have assessed the prevalence of high Lp(a) levels in patients followed at a tertiary hospital specialized in cardiovascular diseases (CVD). In addition, there is scant information about Lp(a) concentrations in Brazilian individuals. Purpose The aim of the study was to describe the demographic characteristics and comorbidities of patients with at least one measure of Lp(a) at a tertiary treatment center for CVD in our city – Brazil. Methods Patients treated at a heart institute had their data extracted between the years 1999 and 2021. Data were obtained through direct electronic extraction of patients' medical records. The patients were categorized according to different Lp(a) cutoff levels (&amp;gt; 50 and &amp;lt; 70, &amp;gt; 70 and &amp;lt; 90, and &amp;gt; 90 mg/dL) and by quartiles. Results Of 4,970 unique patients included in the study, the mean age at baseline was 59.9 years (SD ± 14.5), 2,634 (53%) were male, and the median Lp(a) was 23.2 mg/dL (interquartile range 8.9 - 56.8 mg/dL). In the whole cohort, 460 (9.3%) had Lp(a) &amp;gt; 50 and &amp;lt; 70, 344 (6.9%) &amp;gt; 70 and &amp;lt; 90, 612 (12.3%) &amp;gt; 90 mg/dl and 138 (2.8%) &amp;gt; 150 mg/dL. Established ASCVD was reported in 1,223 (24%) of the individuals, with a progressively higher prevalence across the Lp(a) categories above (31.2%, 33.8%, 34.2%, respectively) (table 1). Moreover, the Lp(a) median (interquartile range) in mg/dL was significantly higher in those with baseline history of ASCVD (31.4 [10.8-71.2] vs 21.2 [8.3-52]), MI (27.8 [10.6-65.9] vs 22.3 [8.5-54.7]) and stroke (24.9 [10-69.5] vs 23.1 [8.9-56.5]), all p &amp;lt; 0.05 (table 2). Lp(a) was also significantly higher among those with LDL-C ≥ 100 mg/dL relative to LDL-C &amp;lt; 100 mg/dl (25.5[9.5-63.2] vs 21.4[8.4 vs 52.2] p &amp;lt; 0.05). Conclusions In this cohort of patients followed at a tertiary center specialized in CVD, approximately a third had Lp(a) levels above 50 mg/dL, a cutoff robustly associated with ASCVD. This finding likely represents an important source of cardiovascular residual risk, particularly in those with established ASCVD, exposing the need of further therapies.

Transient changes in L-arginine, asymmetric and symmetric dimethyl arginine in triathletes following Norseman Xtreme Triathlon.

Arterial vasodilation is dependent on nitric oxide synthesized from L-arginine by endothelial nitric oxide synthase. Triathletes are reported to display altered serum concentrations of nitric oxide metabolites such as L-arginine, asymmetric dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) shortly after completing long-distance triathlon races. In other populations, similar changes to nitric oxide metabolites are established risk markers of cardiovascular disease. The objective of this study was to assess serum concentrations of metabolites for endothelial nitric oxide synthesis in triathletes one week following a long-distance triathlon race. In this prospective observational study, we used high-performance liquid chromatography to measure circulating concentrations of L-arginine, ADMA, and SDMA in triathletes. Venous blood samples were collected before, immediately after, day one, and one week following the triathlon race. Serum concentrations and L-arginine/ADMA ratio were determined for each time-point and compared to baseline. L-arginine/ADMA ratio was reduced on day one (147 ± 32 vs 163 ± 40, p < 0.02). ADMA was reduced immediately after and increased at day one and remained elevated at oneweek (0.29 ± 0.05μM, p < 0.001, 0.44 ± 0.08μM, p < 0.001 and 0.42 ± 0.07μM, p = 0.04, respectively vs 0.40 ± 0.05μM). SDMA was increased at all time-points when compared to baseline (0.48 ± 0.10μM, p < 0.001, 0.53 ± 0.11μM, p < 0.001 and 0.42 ± 0.08μM, p = 0.048 vs 0.38 ± 0.05μM). L-arginine was only decreased immediately after (46.0 ± 9.3μM vs. 64.6 ± 16.1μM, p < 0.001). Long-distance triathlon racing induces altered levels of metabolites for endothelial nitric oxide production that mostly normalizes within one week following racing. The clinical relevance of these transient changes has yet to be elucidated in the athletic population.

High-density lipoprotein functionality in cholesterol efflux in early childhood is related to the content ratio of triglyceride to cholesterol

Cholesterol efflux capacity (CEC), commonly measured as a useful risk marker of atherosclerotic cardiovascular disease, depends on high-density lipoprotein (HDL) functionality and its concentration. We defined the relative HDL functionality in cholesterol efflux, not influenced by HDL concentration, as the ratio of measured CEC to standardized CEC (stCEC) based on HDL-cholesterol (HDL-C) of each individual using the curve regression equation obtained from the correlation. HDL-C, CEC, and CEC/stCEC levels in the < 28-day-old participants (neonates) were significantly low compared to those of the ≥ 28-day-old participants, indicating that the low CEC levels in the neonates depend on not only lower HDL-C but also lower HDL functionality. The low level of CEC/stCEC was remarkable in neonates born at < 34 weeks of gestation and did not improved to the reference level (1.000) until the infantile period. The relatively low or high CEC/stCEC ratios in neonates and infants were associated with lower or higher HDL-TG and HDL-TG/HDL-C ratio, respectively. However, no apparent effect of HDL-TG and HDL-TG/HDL-C ratio on CEC/stCEC was observed in the ≥ 1-year-old participants, indicating that HDL functionality in cholesterol efflux could be associated with the various HDL particles with various lipid compositions, but not just with HDL-TG and HDL-TG/HDL-C ratio.

Combined Effects of Environmental Metals and Physiological Stress on Lipid Dysregulation.

Cardiovascular diseases (CVD) are a leading cause of mortality worldwide, influenced by genetic, environmental, and behavioral factors. This study examines the relationship between heavy metal exposure, chronic physiological stress (allostatic load), and lipid profiles, which are markers of CVD risk, using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. We utilized structural equation modeling (SEM) to explore the associations between blood levels of lead, cadmium, allostatic load (AL), and lipid measures (low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides). The AL index was derived from cardiovascular, inflammatory, and metabolic biomarkers and categorized into quartiles to identify high-risk individuals, with an index out of 10 subsequently developed. The SEM analysis revealed that both heavy metal exposure and allostatic load are significantly associated with lipid profiles. Higher levels of lead and cadmium were associated with increased LDL and triglycerides, while higher AL scores were linked to increased LDL and triglycerides and decreased HDL levels. Age was also a significant factor, showing positive correlations with LDL and triglycerides, and a negative correlation with HDL. This study underscores the multifactorial nature of CVD, highlighting the combined impact of environmental pollutants and physiological stress on lipid dysregulation. These findings suggest the need for integrated public health strategies that address both environmental exposures and chronic stress to mitigate cardiovascular risk. Further research is warranted to explore the underlying mechanisms and develop targeted interventions.

P125 WORKING LONG HOURS DURING MIDLIFE IS LATER ASSOCIATED WITH INCREASED ARTERIAL STIFFNESS

Background and Objectives: Arterial stiffness is an asymptomatic cardiovascular disease (CVD) risk marker, resulting from reduced ability of large proximal arteries to dilate and retract. Arterial stiffness is associated with increased CVD, independently of blood pressure (BP). Evidence suggest that tackling modifiable risk factors may alter the pathogenic process leading to CVD, by reducing arterial stiffness progression. Long working hours is a frequent and modifiable risk factor from the work environment, shown to increase the risk of CVD. There is sparse evidence about the effect of long working hours on arterial stiffness. No previous study have used carotid-femoral pulse wave velocity (PWV), recognized as the reference assessment method. This study aims to examine whether long working hours, repeatedly assessed at midlife, is associated with increased arterial stiffness at older age in a 24-year prospective study of white-collar workers in Quebec City, Canada. Methods: This study relied on a prospective cohort, initiated in 1991-1993 (T1) with two follow-ups after 8 years (T2, 1999-2000) and 24 years (T3, 2015-2018). Participants (N=1,629) were randomly selected for arterial stiffness measurement at T3 using carotid-femoral pulse wave velocity (PWV). Long working hours (&gt;40 h/week) were assessed at baseline (T1) and at the first follow-up (T2). Mean differences in PWV were estimated using generalized linear models, accounting for sociodemographic factors, lifestyle-related risk factors, clinical factors and psychosocial stressors at work. Results: Among participants who remained actively employed over the study period, baseline (+0.54 m/s, 95% CI: 0.05 – 1.02) and repeated (+1.54 m/s, 95% CI: 0.83 – 2.26) exposures to long working hours were associated with increased arterial stiffness. No association was observed among participants who retired between follow-ups. Conclusions: Working long hours during midlife is associated with increased arterial stiffness, among aging workers. Workplace preventive strategies reducing long working hours may be effective to mitigate long-term arterial stiffening.

Perivascular Fat: A Novel Risk Factor for Coronary Artery Disease.

Perivascular adipose tissue (PVAT) interacts with the vascular wall and secretes bioactive factors which regulate vascular wall physiology. Vice versa, vascular wall inflammation affects the adjacent PVAT via paracrine signals, which induce cachexia-type morphological changes in perivascular fat. These changes can be quantified in pericoronary adipose tissue (PCAT), as an increase in PCAT attenuation in coronary computed tomography angiography images. Fat attenuation index (FAI), a novel imaging biomarker, measures PCAT attenuation around coronary artery segments and is associated with coronary artery disease presence, progression, and plaque instability. Beyond its diagnostic capacity, PCAT attenuation can also ameliorate cardiac risk stratification, thus representing an innovative prognostic biomarker of cardiovascular disease (CVD). However, technical, biological, and anatomical factors are weakly related to PCAT attenuation and cause variation in its measurement. Thus, to integrate FAI, a research tool, into clinical practice, a medical device has been designed to provide FAI values standardized for these factors. In this review, we discuss the interplay of PVAT with the vascular wall, the diagnostic and prognostic value of PCAT attenuation, and its integration as a CVD risk marker in clinical practice.

Ten-year cardiovascular disease risk and related factors in lifetime marijuana use with comorbid methamphetamine-associated psychotic disorder: a QRISK®3 study

BackgroundMethamphetamine use and related direct and indirect problems are increasing all over the world. The coexistence of lifetime marijuana use (LMU) and methamphetamine use disorder (MUD) may also be accompanied by psychotic symptoms (MAP). Methamphetamine and marijuana use are known to pose risks for cardiovascular diseases (CVDs). However, ten-year CVD risk and inflammation markers of LMU-MUD (non-psychosis group) and LMU-MAP (psychosis group) subjects and the relationship of various sociodemographic and clinical variables with these markers have not yet been examined.MethodsThirty-two male subjects were included in non-psychosis group and 72 male subjects in psychosis group. Sociodemographic and clinical characteristics were recorded. Psychotic symptom severity of psychosis group subjects was measured. The ten-year CVD risk was calculated using QRISK®3 model.ResultsAge, cigarettes/pack-years, alcohol use onset age, drug use onset age, methamphetamine use onset age, duration of methamphetamine use, education and marital status of the groups were similar (p > 0.05). There was a statistical difference between the non-psychosis and psychosis groups in terms of self-mutilation history (p < 0.001), suicidal attempt history (p = 0.007), homicidal attempt history (p = 0.002), psychiatric hospitalization history (p = 0.010). Ten-year QRISK®3 score was 4.90 ± 9.30 in the psychosis group, while it was 1.60 ± 1.43 in the non-psychosis group (p = 0.004). The mean heart age of the psychosis group was 14 years higher than their chronological age, while the mean heart age of the non-psychosis group was 8 years higher. Neutrophil to lymphocyte ratio (NLR) (p = 0.003) was higher in the psychosis group. A significant correlation was detected between ten-year QRISK®3 and positive psychotic symptoms in the psychosis group (r = 0.274, p = 0.020). Regression analysis showed that self-mutilation history, NLR and relative risk obtained from QRISK®3 can be used to distinguish non-psychosis group and psychosis group subjects (sensitivity = 91.7; Nagelkerke R2 0.438; p = 0.001).ConclusionsThis study is important as it demonstrates for the first time that among the subjects using marijuana and methamphetamine, those with psychotic symptoms have a higher NLR and ten-year CVD risk.

Cardiovascular disease risk factors and their associations with inflammation among US adolescents: NHANES, 2015 to March 2020

IntroductionThe prevalence of obesity and glycemic dysfunction in adolescents has increased over the past several decades but less is known on how these conditions are associated with systemic inflammation in...

Variation of LDL cholesterol in response to the replacement of saturated with unsaturated fatty acids: a nonrandomized, sequential dietary intervention; the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention (“RISSCI”-1) study

BackgroundSerum low density lipoprotein (LDL) cholesterol shows marked interindividual variation in response to the replacement of saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs). ObjectivesTo demonstrate the efficacy of United Kingdom guidelines for exchanging dietary SFAs for UFAs, to reduce serum LDL cholesterol and other cardiovascular disease (CVD) risk factors, and to identify determinants of the variability in LDL cholesterol response. MethodsHealthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2), consumed a higher-SFA/lower-UFA diet for 4 wk, followed by an isoenergetic, lower-SFA/higher-UFA diet for 4 wk (achieved intakes SFA:UFA as % total energy 19.1:14.8 and 8.9:24.5, respectively). Serum LDL cholesterol, CVD risk markers, peripheral blood mononuclear cell (PBMC) gene expression, and dietary intakes were assessed at baseline and the end of each diet. ResultsTransition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet significantly reduced fasting blood lipids: LDL cholesterol (−0.50 mmol/L; 95% confidence interval [CI]: −0.58, −0.42), high-density lipoprotein (HDL) cholesterol (−0.11 mmol/L; 95% CI: −0.14, −0.08), and total cholesterol (TC) (−0.65 mmol/L; 95% CI:−0.75, −0.55). The dietary exchange also reduced apolipoprotein (apo)B, TC:HDL cholesterol ratio, non-HDL cholesterol, E-selectin (P < 0.0001), and LDL subfraction composition (cholesterol [LDL-I and LDL-II], apoB100 [LDL-I and LDL-II], and TAG [LDL-II]) (P < 0.01). There was also an increase in plasma biomarkers of cholesterol intestinal absorption (β-sitosterol, campesterol, cholestanol), and synthesis (desmosterol) (P < 0.0001) and fold change in PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet (P = 0.035). Marked interindividual variation in the change in serum LDL cholesterol response (−1.39 to +0.77 mmol/L) to this dietary exchange was observed, with 33.7% of this variation explained by serum LDL cholesterol before the lower-SFA/higher-UFA diet and reduction in dietary SFA intake (adjusted R2 27% and 6.7%, respectively). APOE genotype was unrelated to serum LDL cholesterol response to SFA. ConclusionsThese findings support the efficacy of United Kingdom SFA dietary guidelines for the overall lowering of serum LDL cholesterol but showed marked variation in LDL cholesterol response. Further identification of the determinants of this variation will facilitate targeting and increasing the efficacy of these guidelines.The RISSCI-1 study was registered with ClinicalTrials.Gov (No. NCT03270527).

Associations between Supper Timing and Mortality from Cardiovascular Disease among People with and without Hypertension.

Less is known about the impact of supper time on cardiovascular disease (CVD) risk among hypertensives and nonhypertensives. We aimed to explore this issue in a cohort study. We analyzed the data of 72,658 participants (15,386 hypertensives and 57,272 nonhypertensives) aged 40-79 years without a history of CVD at baseline (1988-1990) under the Japan Collaborative Cohort study. Supper time was assessed based on self-reported questionnaires categorized as before 17:00, between 17:00 and 20:00, after 20:00, irregular supper time, and reference supper time (17:00-20:00). Hazard ratios (HRs) and 95% confidence intervals (95% CI) of CVD mortality were calculated according to supper time after adjustment for potential confounders, stratified by hypertensive status and age group (＜65 and ≥ 65 years). During a median of 19.4 years of follow-up, 4,850 CVD deaths were recorded. Compared with the reference time, the risk of CVD mortality was higher for irregular supper time for the total population, either hypertensives or nonhypertensives, more specifically hypertensives aged ≥ 65 years; the multivariable HR (95% CI) of CVD mortality in the total population was 1.28 (1.11-1.50, P＜0.01). The supper time of ＞20:00 tended to be associated with the higher risk only for hypertensives; the multivariable HR was 1.39 (0.98-1.96, P=0.06). Irregular supper time was associated with an increased risk of CVD mortality. Supper timing could be a surrogate marker for CVD risk.

Proceedings of PRINCETON IV: PDE5 inhibitors and cardiac health symposium.

Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023. Our meeting aimed to update existing knowledge, assess current guidelines, and make recommendations for future research and practice in this area. An expert panel reviewed existing research and clinical practice guidelines. Key findings and clinical recommendations are the following: First, erectile dysfunction (ED) is a risk marker and enhancer for cardiovascular (CV) disease. For men with ED and intermediate levels of CV risk, coronary artery calcium (CAC) computed tomography should be considered in addition to previous management algorithms. Second, sexual activity is generally safe for men with ED, although stress testing should still be considered for men with reduced exercise tolerance or ischemia. Third, the safety of PDE5 inhibitor use with concomitant medications was reviewed in depth, particularly concomitant use with nitrates or alpha-blockers. With rare exceptions, PDE5 inhibitors can be safely used in men being treated for hypertension, lower urinary tract symptoms and other common male disorders. Fourth, for men unresponsive to oral therapy or with absolute contraindications for PDE5 inhibitor administration, multiple treatment options can be selected. These were reviewed in depth with clinical recommendations. Fifth, evidence from retrospective studies points strongly toward cardioprotective effects of chronic PDE5-inhibitor use in men. Decreased rates of adverse cardiac outcomes in men taking PDE-5 inhibitors has been consistently reported from multiple studies. Sixth, recommendations were made regarding over-the-counter access and potential risks of dietary supplement adulteration. Seventh, although limited data exist in women, PDE5 inhibitors are generally safe and are being tested for use in multiple new indications. Studies support the overall cardiovascular safety of the PDE5 inhibitors. New indications and applications were reviewed in depth.

Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention.

Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care. A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C. ApoB was highly correlated with LDL-C and non-HDL-C (Pearson's r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8-108.8 md/dL when LDL-C 130 mg/dL, 88.3-112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8-147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean - 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0-1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03-1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12-1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model. High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.

Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk

RationaleLung function in early adulthood is associated with subsequent adverse health outcomes.ObjectivesTo ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association...

The Influence of Early Menopause on Baroreflex Sensitivity in Healthy Females

Introduction: The risks of hypertension (HTN) and cardiovascular disease (CVD) rise dramatically in females around the typical age of menopause (TM; menopause age ≥46yr). Early menopause (EM; menopause age &lt;46yr) may substantially increase this risk. Attenuated baroreflex sensitivity (BRS) can be indicative of autonomic dysfunction and has been shown to be a marker of CVD risk. Thus, we aimed to investigate how EM would influence BRS. We hypothesized that females who experienced EM would exhibit attenuated BRS compared to females who experienced TM. Methods: 32 females completed two visits: Visit 1: informed consent, medical and health questionnaires to confirm eligibility, including the Minnesota Leisure Time Physical Activity Questionnaire to assess activity levels. Visit 2: Participants rested in a supine position for 10 min. Non-invasive beat-to-beat blood pressure (BP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were recorded. Blood was drawn to measure sex steroid levels. Cardiovagal (cBRS) and sympathetic (sBRS) BRS were calculated using the sequence method and Ensemble software, respectively. Both parametric and non-parametric methods were used for the statistical analysis. Results: Results are presented as mean ± SD. Participants in the TM (n=16; age: 63±3yrs, body-mass index (BMI): 25±4kg/m2) and EM (n=16; age: 62±4yrs, BMI: 26±4kg/m2) groups were matched for age and BMI. TM and EM had similar levels of estradiol (TM: 3.9±2; EM: 4.4±4pg/mL) and activity levels (TM: 299±177; EM: 208±147kcal/day), but significantly different menopause ages (TM: 51±3; EM: 43±2yrs; p&lt;0.001). TM and EM had similar resting systolic BP (TM: 129±13; EM: 128±20mmHg), diastolic BP (TM: 79±10; EM: 82±14mmHg), HR (TM: 59±7bpm; EM: 62±9bpm), and MSNA (TM: 51±16; EM: 45±11bursts/100heartbeats), p&gt;0.05 for all. Further, cBRS and sBRS were similar between TM (cBRSup: 9.7±3; cBRSdown: 12.3±7; cBRStotal: 12.3±7ms/mmHg; sBRS: -2.7±1bursts/100Hb/mmHg) and EM (cBRSup: 8.7±4; cBRSdown: 11±5; cBRStotal: 10.4±4ms/mmHg; sBRS: -2±1bursts/100Hb/mmHg; p&gt;0.05 for all). Conclusion: Contrary to our hypothesis, these findings suggest that EM may not influence BRS. These findings indicate that completing menopause early may not disrupt autonomic baroreflex function, suggesting that other mechanisms need to be explored to better understand the increased CVD risk in postmenopausal females who complete menopause prematurely or early. This study was supported by a NIH 1 K01 AG064038-01A1 (MLKR), UMN Grant-in-Aid (MLKR), F32HL160012 (EL), and NIH National Center for Advancing Translational Sciences grant UL1TR002494. This is the full abstract presented at the American Physiology Summit 2024 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.

Impact of Biologic Therapy on Key Cardiovascular Risk Parameters in a Psoriatic Cohort-a Retrospective Review.

Psoriasis is a risk factor for cardiovascular disease. Biologic agents have revolutionised psoriatic skin control. This study aims to assess the change in cardiovascular risk factors in a cohort of patients treated with 1 year of continuous biologic treatment. A retrospective medical record review was conducted of consecutive patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Australia. The effect of biologic therapy on psoriasis was assessed using a psoriasis area severity index (PASI). Cardiovascular risk factors included systolic blood pressure (SBP), diastolic BP (DBP), heart rate (HR) and body mass index (BMI). Measurements at baseline and 1-year follow-up were compared using paired t-tests. A total of 106 patients were reviewed with a median age of 44 years, and 63% of the patients were male. At baseline, mean BMI was 30 (SD 7), mean SBP was 129 (SD 17), mean DBP was 81 (SD 9) and mean HR was 82 (SD 14). Over 12months, the PASI was reduced from 17.4 (SD 8.5) to 1.4 (SD 1.7, p < 0.001) indicating skin improvement. There was no significant difference from baseline in SBP (difference 2.3mmHg, 95% CI - 1.4-5.9), DBP (0.6mmHg, 95% CI - 1.2-2.5), BMI (difference - 0.1kg/m2, 95% CI - 0.9-0.7) or HR (difference 1.3, 95% CI - 3.9-6.4). In patients with psoriasis, markers of cardiovascular disease risk did not improve after 1year of biologic therapy despite significant improvements in psoriasis skin severity.