Inflammatory illnesses, such as periodontitis and atherosclerotic coronary heart disease (ASCHD), trigger the production of pro-inflammatory mediators. The aim of this study was to assess the accuracy of using salivary interleukin-1β (IL-1β), interleukin-18 (IL-18), and gasdermin D (GSDMD) in discerning patients with periodontitis with and without ASCHD from healthy individuals, and to assess their correlation with clinical periodontal parameters and low-density lipoprotein (LDL) levels. The study involved 120 participants: 30 were healthy subjects (control group, C), 30 had generalized periodontitis (group P), 30 had ASCHD and clinically healthy periodontium (group AS-C), and 30 had ASCHD and generalized periodontitis (group AS-P). Saliva and blood samples were collected, and periodontal characteristics such as plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss were examined. IL-1β, IL-18, and GSDMD levels from saliva were determined using ELISA. LDL levels were determined from the blood samples. Groups P, AS-C, and AS-P had higher levels of salivary IL-1β, IL-18, and GSDMD than group C. The receiver operating characteristic (ROC) curves of all biomarkers showed high diagnostic accuracy, with a significant positive correlation with the clinical parameters and LDL levels. The observed correlations between the studied pro-inflammatory mediators and disease severity suggest that these biomarkers could serve as indicators of disease progression in conditions such as periodontitis and ASCHD.

Numerous studies have established a link between gene variants within the inflammasome complex and the incidence of periodontitis and cardiovascular illness across various ethnic groups. This study investigated the association between PYCARD gene polymorphism and susceptibility to periodontal disease and coronary heart disease (CHD) and their correlation with clinical periodontal indices. A total of 120 participants were enrolled, categorized into four groups: 30 healthy controls (C), 30 patients with generalized periodontitis (P), 30 patients with atherosclerotic CHD but clinically healthy periodontium (AS-C), and 30 patients with both atherosclerotic CHD and generalized periodontitis (AS-P). We recorded demographic data, collected blood samples, and measured periodontal indices, including plaque index, clinical attachment loss, bleeding on probing, and pocket depth. The genomic variant of the PYCARD gene was analyzed using a conventional polymerase reaction. A significant prevalence of T and G allele mutations and a higher distribution of CT and TT genotypes in PYCARD C/T (rs8056505) and the AG genotype in PYCARD A/G (rs372507365) were observed in groups P, AS-P, and AS-C. These single nucleotide polymorphisms (SNPs) were also positively correlated with the severity of clinical periodontitis indices. Our findings suggest that the increased frequency of T and G alleles and the distribution of CT, TT, and AG genotypes in PYCARD SNPs are significantly associated with an elevated risk for periodontal disease and CHD. These SNPs may participate in the pathogenesis of these conditions. The study reinforces the potential role of these genetic markers as risk factors for both diseases in the Iraqi population.

UNASSIGNED: We aimed to estimate the future burden of coronary heart disease (CHD) and stroke mortalities by sex and all 47 prefectures of Japan until 2040 while accounting for effects of age, period, and cohort and integrating them to be at the national level to account for regional differences among prefectures.
UNASSIGNED: We estimated future CHD and stroke mortality projections, developing Bayesian age-period-cohort (BAPC) models in population and the number of CHD and stroke by age, sex, and all 47 prefectures observed from 1995 to 2019; then applying these to official future population estimates until 2040. The present participants were all men and women aged over 30 years and were residents of Japan.
UNASSIGNED: In the BAPC models, the predicted number of national-level cardiovascular deaths from 2020 to 2040 would decrease (39,600 [95% credible interval: 32,200-47,900] to 36,200 [21,500-58,900] CHD deaths in men, and 27,400 [22,000-34,000] to 23,600 [12,700-43,800] in women; and 50,400 [41,900-60,200] to 40,800 [25,200-67,800] stroke deaths in men, and 52,200 [43,100-62,800] to 47,400 [26,800-87,200] in women).
UNASSIGNED: After adjusting these factors, future CHD and stroke deaths will decline until 2040 at the national level and in most prefectures.
UNASSIGNED: This research was supported by the Intramural Research Fund of Cardiovascular Diseases of the National Cerebral and Cardiovascular Center (21-1-6, 21-6-8), JSPS KAKENHI Grant Number JP22K17821, and the Ministry of Health, Labour and Welfare Comprehensive Research on Life-Style Related (Diseases Cardiovascular Diseases and Diabetes Mellitus Program), Grant Number 22FA1015.

UNASSIGNED: Previous studies suggested that vasomotor symptoms were associated with an increasing risk of coronary heart diseases (CHD) but not clear with menopausal symptoms other than vasomotor symptoms. Given the heterogeneity and interrelationship among menopausal symptoms, it is not easy to make causal inferences based on observational studies. We performed a Mendelian randomization (MR) to investigate the association of individual non-vasomotor menopausal symptoms and the risk of CHDs.
UNASSIGNED: A sample of 177,497 British women aged ≥51 years old (average age at menopause) without related cardiovascular diseases from the UK biobank is selected as our study population. Non-vasomotor menopausal symptoms, including anxiety, nervous, insomnia, urinary tract infection, fatigue, and vertigo, were selected as exposures based on the modified Kupperman index. Outcome variable is CHD.
UNASSIGNED: In total, 54, 47, 24, 33, 22, and 81 instrumental variables were selected for anxiety, insomnia, fatigue, vertigo, urinary tract infection and nervous respectively. We conducted MR analyses of menopausal symptoms and CHD. Only insomnia symptoms increased the lifetime risk of CHD with OR 1.394 (p = 0.0003). There were no significant causal relationships with CHD and other menopausal symptoms. Insomnia near menopause age (45-50 years) does not increase the risk of CHD. However, postmenopausal (over 51) insomnia increases the risk of CHD.
UNASSIGNED: MR analyses support that among non-vasomotor menopausal symptoms, only insomnia symptoms may increase the lifetime risk of CHD. Insomnia at different ages near menopause has differential impacts on CHD risk.

Stroke risk is currently estimated as part of the composite risk of cardiovascular disease (CVD). We investigated if composite-CVD risk prediction tools QRISK3 and Pooled Cohort Equations-PCE, derived from middle-aged adults, are as good as stroke-specific Framingham Stroke Risk Profile-FSRP and QStroke for capturing the true risk of stroke in older adults. External validation for 10y stroke outcomes was performed in men (60-79y) of the British Regional Heart Study. Discrimination and calibration were assessed in separate validation samples (FSRP n = 3762, QStroke n = 3376, QRISK3 n = 2669 and PCE n = 3047) with/without adjustment for competing risks. Sensitivity/specificity were examined using observed and clinically recommended thresholds. Performance of FSRP, QStroke and QRISK3 was further compared head-to-head in 2441 men free of a range of CVD, including across age-groups. Observed 10y risk (/1000PY) ranged from 6.8 (hard strokes) to 11 (strokes/transient ischemic attacks). All tools discriminated weakly, C-indices 0.63-0.66. FSRP and QStroke overestimated risk at higher predicted probabilities. QRISK3 and PCE showed reasonable calibration overall with minor mis-estimations across the risk range. Performance worsened on adjusting for competing non-stroke deaths. However, in men without CVD, QRISK3 displayed relatively better calibration for stroke events, even after adjustment for competing deaths, including in oldest men. All tools displayed similar sensitivity (63-73 %) and specificity (52-54 %) using observed risks as cut-offs. When QRISK3 and PCE were evaluated using thresholds for CVD prevention, sensitivity for stroke events was 99 %, with false positive rate 97 % suggesting existing intervention thresholds may need to be re-examined to reflect age-related stroke burden.

UNASSIGNED: Although homeostasis of the cardiovascular system is regulated by the cerebral cortex via the autonomic nervous system, the role of abnormal brain functional connectivity (FC) networks in patients with cardiac dysfunction remains unclear. Here, we report thalamus-based FC alterations and their relationship with clinical characteristics in patients with coronary heart disease (CHD).
UNASSIGNED: We employed resting-state functional magnetic resonance imaging (rs-fMRI) to acquire imaging data in twenty-six patients with CHD alongside sixteen healthy controls (HCs). Next, we performed a thalamus-based FC analysis to profile abnormal FC patterns in the whole brain. Subsequently, the mean time series of the brain regions that survived in the FC analysis were used to determine correlations with clinical parameters in patients with CHD.
UNASSIGNED: We found no statistically significant differences in demographic and clinical data between patients with CHD and HCs. Patients with CHD showed decreased FC patterns between bilateral thalami and left hemisphere, encompassing supplementary motor area, superior frontal gyrus, superior parietal gyrus, inferior parietal gyrus, middle cingulate cortex, lingual gyrus and calcarine sulcus.
UNASSIGNED: These findings not only have implications in clarifying the relationship between cerebral functional imbalance and cardiovascular system, but also provide valuable insights to guide future evaluation and management of cardiac autonomic regulation via the brain-heart axis.

UNASSIGNED: Lower prevalence of major cardiovascular disease (CVD) risk factors, such as dyslipidemia, hypertension and smoking, can explain a substantial part of the decline in CVD mortality and incidence for the past decades in Western countries. However, some studies have indicated less favorable trends in risk factors in recent years. We have assessed time trends in lipid profiles among young adults in Norway measured between 2001 and 2019.
UNASSIGNED: Samples of serum lipids analyzed at one large medical laboratory in Oslo, Norway, mainly requisitioned by primary care physicians, were analyzed cross-sectionally to estimate year-to-year trends among men and women aged 18-49 years. We also assessed the lipid distributions and proportions with adverse lipid levels.
UNASSIGNED: In total, more than 2,6 million blood samples, comprising more than 1 million individuals (mean age 37.7 years) from all regions of Norway were included. All measures improved among all age groups in both women and men, especially in total and non-HDL cholesterol (-0.22 and -0.25 mmol/l per decade, respectively). There were downward shifts in the population distribution of total, non-HDL-C and LDL-C. The overall prevalences of total cholesterol ≥5.0 mmol/l and non-HDL-C ≥3.9 mmol/l similarly decreased, from ∼63 to 46% and from ∼52 to 34%, respectively. More than 1/3 had elevated levels of total and/or non-HDL-C in 2019.
UNASSIGNED: In a large proportion of the Norwegian population aged 18-49 years old, the lipid profiles improved during the last two decades. As the use of lipid-lowering medications is low in this age group, this likely reflects favorable secular trends.

UNASSIGNED: Oxidized LDL (oxLDL) is formed by the spontaneous reaction between aldehyde byproducts of lipid peroxidation and lysine residues of apolipoprotein B within LDL. Clinically, oxLDL is used as a marker of coronary artery disease and predictor of metabolic syndrome risk. Despite its popularity as a clinical marker, no systematic studies of oxLDL stability, in which serum or plasma has been pre-analytically exposed to an array of different time and temperature conditions, have been carried out.
UNASSIGNED: To systematically evaluate the stability of oxLDL in human serum samples exposed to thawed conditions (> -30 °C) for varying periods of time while monitoring a second protein/small molecule redox system as a positive control for non-enzymatic biomolecular activity.
UNASSIGNED: OxLDL was measured in serum samples, from 24 different humans, that had been pre-exposed to three different time courses at 23 °C, 4 °C and -20 °C using ELISA kits from Mercodia that employ the 4E6 mouse monoclonal antibody. A liquid chromatography/mass spectrometry-based marker of serum exposure to thawed conditions known as ΔS-Cys-Albumin was employed as a positive control.
UNASSIGNED: OxLDL was stable in serum exposed to 23 °C for up to 48 h, 4 °C for 21 days, or -20 °C for 65 days. ΔS-Cys-Albumin changed dramatically during these time courses (p < 0.001).
UNASSIGNED: OxLDL is remarkably stable ex vivo in human serum samples exposed to thawed conditions.

UNASSIGNED: Contemporary prevalence, awareness, and control of severe hypercholesterolemia (SH) and familial hypercholesterolemia (FH) and the associated atherosclerotic cardiovascular disease risk in the US are unknown.
UNASSIGNED: Using electronic health records, we assessed the burden of SH and FH in Olmsted County, Minnesota, US, between 2004 and 2015. We defined SH as low-density lipoprotein cholesterol (LDL-C) level ≥190 mg/dl without secondary causes of hypercholesterolemia and FH as a Dutch Lipid Clinic Network score ≥6. Controls were age- and sex-matched individuals with LDL-C level <190 mg/dl.
UNASSIGNED: The age- and sex-adjusted point and period prevalence (age-recursive method) of SH was 4.44% and 8.95%, respectively; 1 in 21 had FH (∼1:233 adults), and 46.2% had a recorded diagnosis. Guideline recommended targets (LDL-C <100 mg/dl and <70 mg/dl in the primary and secondary prevention settings, respectively) were achieved in 33.1% and 21.2% of SH cases, with less women overall achieving the target than men (18.6% vs. 23.7%, p=0.022). After adjustment for conventional risk factors, the hazard ratio for incident coronary heart disease (CHD) in those with SH was 1.21 (1.05-1.39; p=0.010), in those with SH and a family history of CHD was 2.16 (1.57-2.96; p<0.001) and in those with FH was 4.61 (2.66-7.97; p<0.001). The association of SH with CHD was modified by age (p-interaction = 0.015), such that the risk was greater at younger ages.
UNASSIGNED: SH was prevalent and an independent risk factor for incident CHD. Awareness and control were low, highlighting a treatment gap (more prominent in women) that needs to be addressed.

Atherosclerotic cardiovascular disease (ASCVD) is epidemic throughout the world and is etiologic for such acute cardiovascular events as myocardial infarction, ischemic stroke, unstable angina, and death. ASCVD also impacts risk for dementia, chronic kidney disease peripheral arterial disease and mobility, impaired sexual response, and a host of other visceral impairments that adversely impact the quality and rate of progression of aging. The relationship between low-density lipoprotein cholesterol (LDL-C) and risk for ASCVD is one of the most highly established and investigated issues in the entirety of modern medicine. Elevated LDL-C is a necessary condition for atherogenesis induction. Basic scientific investigation, prospective longitudinal cohorts, and randomized clinical trials have all validated this association. Yet despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial and primary prevention more serously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs. Herein we discuss the need to greatly intensify efforts to reduce risk, decrease disease burden, and provide more comprehensive and earlier risk assessment to optimally prevent ASCVD and its complications. Evidence is presented to support that treatment should aim for far lower goals in cholesterol management, should take into account many more factors than commonly employed today and should begin significantly earlier in life.