Occurrence Of Cardiovascular Disease Events Research Articles

Association between atherogenic index of plasma and future risk of cardiovascular disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3: a nationwide prospective cohort study

BackgroundAs an emerging concept, Cardiovascular-kidney-metabolic syndrome (CKM) elucidates the intricate interconnection between metabolic disorders(Mets), cardiovascular disease(CVD), and chronic kidney disease(CKD). Within this context, while numerous studies have demonstrated a correlation between the Atherogenic Index of Plasma (AIP) and CVD, the precise relationship between long-term fluctuations in the AIP and the incidence of CVD in patients with CKM syndrome remains unclear.MethodThe CKM stages 0–3 population was obtained from the China Health and Retirement Longitudinal Study (CHARLS). The outcome CVD was defined as self-reported heart disease and/or stroke. AIP control level was classified using k-mean cluster analysis. Logistic regression was used to analyse the effect of cumulative AIP (cumAIP) on the incidence of CVD. Restricted cubic spline models (RCS) were used to explore the potential non-linear relationship between cumulative AIP and CVD risk at different CKM syndrome stages.ResultsOf the 3429 CKM stages 0–3 participants, 620 patients developed CVD during the 3-year follow-up period. After adjusting for various confounders, the odds ratio (OR) for the well-controlled class 2 compared with the best AIP control class 1 were 1.37 (1.04, 1.81), the OR for the moderately-controlled class 3 were 1.54 (95% CI, 1.04–2.26), the poorly-controlled class 4 were 1.65 (95% CI, 1.13–2.41), and the worst-controlled class 5 were 2.14 (95% CI, 1.15–3.97). In restricted cubic spline regression analyses, changes in AIP were linearly associated with the occurrence of CVD events. Further weighted quartiles and regression analyses indicated that triglyceride(TG) was a key variable for AIP in predicting CVD events in the CKM stages 0–3 population.ConclusionsPoor control level of AIP are associated with an increased risk of CVD events in the population of CKM stages 0–3. Long-term dynamic monitoring of changes in AIP may help in the early identification of patients at high risk of developing CVD in the individuals with CKM stages 0–3.

Association between renal function trajectories and risk of cardiovascular disease: a prospective cohort study

Introduction It is unclear whether changing trajectories of renal function will increase the risk prediction information of cardiovascular disease (CVD). This study aimed to evaluate the trajectory patterns of estimated glomerular filtration rate (eGFR) and the association between eGFR trajectories and CVD risk. Methods A total of 4742 participants were included in the cohort from the 51st Regiment of Xinjiang Production and Construction Corps. The study endpoint was the occurrence of CVD events. eGFR trajectories were identified using a linear mixed-effects model in four distinct patterns. Multivariate Cox proportional hazards models analysed the correlations between eGFR trajectories and CVD. Results During a median follow-up period of 5.7 years, a total of 559 (11.8%) CVD, 404 (8.5%) myocardial infarction (MI), 244 (5.2%) ischemic stroke (IS), and 62 (1.3%) heart failure (HF) incidents occurred. After multivariable adjustment, gradual decline trajectory increased the risk of CVD (HR 1.42, 95% CI 1.16–1.74), MI (HR 1.41, 95% CI 1.11–1.79), and IS (HR 1.41, 95% CI 1.04–1.92); gradual increase trajectory reduced the risk of CVD (HR 0.40, 95% CI 0.25–0.64) and MI (HR 0.49, 95% CI 0.29–0.81). Consistent results were obtained in sensitivity and subgroup analyses. Conclusions Decline and increase of renal function were related to the risk of CVD, MI, and IS in the rural areas of Xinjiang. Monitoring eGFR changing trajectory is of great significance in improving the risk of CVD.

#2496 ASSOCIATION OF ABNORMALITIES IN ELECTROCARDIOGRAPHY AND ECHOCARDIOGRAPHY WITH THE OCCURRENCE OF CARDIOVASCULAR DISEASE IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims In chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) increases along with CKD progression. Although coronary artery disease (CAD) is one of the most critical CVDs, it is difficult to identify CAD because its symptom is usually atypical in CKD. Consequently, appropriate screening tests for CVD are important in this population. Electrocardiography (ECG) and transthoracic echocardiography (TTE) are commonly performed in daily clinical practice, and we researched whether these abnormalities are risk factors for CVD including CAD in patients with advanced CKD. Method This study included patients with CKD stage G4-5 who were admitted to our hospital from 2010 to 2019. Depending on the presence of ECG and/or TTE-indicated abnormalities, the study patients were divided into four groups: those without both ECG and TTE abnormalities (group A: ECG-, TTE-), those with only ECG abnormalities (group B: ECG+, TTE-), those with only TTE abnormalities (group C: ECG-, TTE+), and those with both ECG and TTE abnormalities (group D: ECG+, TTE+). The clinical characteristics, the occurrence of CVD events, their prognosis, and the prevalence of positive screening tests for CAD were compared among the four groups. CVD events were defined as CVD death and non-fatal CVD events. Results The number of study patients was 607, and they were divided into four groups as follows: 333 in group A, 106 in group B, 76 in group C, and 92 in group D, respectively. The median observational period was 21 months. The incidence of CVD events was highest in group D: 45 patients (13.5%) in group A, 25 patients (23.6%) in group B, 19 patients (25.0%) in group C, and 37 patients (40.2%) in group D, respectively. Multivariate analysis showed that the hazard ratios (HR) for CVD events was significantly higher in group C and D compared to group A as reference (HR: 1.620 in group B, p = 0.116; HR: 2.848 in group C, p = 0.001, and 4.111 in group D, p<0.001, respectively). Furthermore, group D had a higher positive rate of screening tests for CAD compared to the other three groups. Conclusion In patients with advanced CKD, ECG and TTE abnormalities were significantly associated with the occurrence of CVD events. Additionally, those with both ECG and TTE abnormalities may be at high risk for the presence of CAD.

Development and Validation of a Nomogram to Predict the Future Risk of Cardiovascular Disease.

Early identification of individuals at a high risk of cardiovascular disease (CVD) is crucial. This study aimed to construct a nomogram for CVD risk prediction in the general population. This retrospective study analyzed the data between January 2012 and September 2020 at the Physical Examination Center of the Second Affiliated Hospital of Nanjing Medical University (randomized 7:3 to the training and validation cohorts). The outcome was the occurrence of CVD events, which were defined as sudden cardiac death or any death related to myocardial infarction, acute exacerbation of heart failure, or stroke. The least absolute shrinkage and selection operator (LASSO) method and multivariate logistic regression were applied to screen the significant variables related to CVD. Among the 537 patients, 54 had CVD (10.1%). The median cardiac myosin-binding protein-C (cMyBP-C) level in the CVD group was higher than in the no-CVD group (42.25 pg/mL VS 25.00 pg/mL, p = 0.001). After LASSO selection and multivariable analysis, cMyBP-C (Odds ratio [OR] = 1.004, 95% CI [CI, confidence interval]: 1.000-1.008, p = 0.035), age (OR = 1.023, 95% CI: 0.999-1.048, p = 0.062), diastolic blood pressure (OR = 1.025, 95% CI: 0.995-1.058, p = 0.103), cigarettes per day (OR = 1.066, 95% CI: 1.021-1.113, p = 0.003), and family history of CVD (OR = 2.219, 95% CI: 1.003-4.893, p = 0.047) were associated with future CVD events (p 0.200). The model, including cMyBP-C, age, diastolic blood pressure, cigarettes per day, and family history of CVD, displayed a high predictive ability with an area under the curve (AUC) of 0.816 (95% CI: 0.714-0.918) in the training cohort (specificity and negative predictive value of 0.92 and 0.96) and 0.774 (95% CI: 0.703-0.845) in the validation cohort. A nomogram based on cMyBP-C, age, diastolic blood pressure, cigarettes per day, and family history of CVD was constructed. The model displayed a high predictive ability.

The relationship between platelet distribution width and new-onset cardiovascular disease events in patients with peritoneal dialysis

Objectives The global mortality rate from chronic kidney disease (CKD) has increased over the past two decades. Typically, peritoneal dialysis (PD) remains a useful alternative treatment for end-stage renal disease. Cardiovascular disease (CVD) is the main complication in PD patients. In terms of prognosis, it is reported that platelet distribution width (PDW) can predict adverse CVD events. However, the relationship between PDW and new-onset CVD in PD patients is not clear. This study aimed to explore the relationship between PDW and new-onset CVD in PD patients. Methods This was a retrospective cohort study, from 4 July 2005 to 31 December 2019, and a total of 1557 patients were recruited. PDW was respectively categorized into two groups: PDW ≤13.2 fL and PDW >13.2 fL. The primary outcome was a new-onset CVD event. Cox proportional hazards models were performed to assess the hazard ratio (HR). Receiver-operating characteristic (ROC) curves were applied to evaluate the predictive accuracy of the PDW on CVD events. Results During follow-up, 114 new-onset CVD events were recorded. Cox proportional hazards models showed a higher risk of CVD events in patients with high PDW (HR = 1.862 95%CI 1.205–2.877, p = 0.005). Kaplan–Meier cumulative incidence curves showed the risk of the first occurrence of CVD events was greater in the high PDW group (p = 0.006). Conclusions High PDW is associated with new-onset cardiovascular disease events in PD patients.

Highlights in ASCVD Primary Prevention for2021.

This review examines key studies published in 2021 that are related to primary prevention of atherosclerotic cardiovascular disease (ASCVD). Major randomized clinical trials (RCTs) concerning traditional risk factors or ASCVD events, meta‐analyses, and key observational studies related to primary prevention of ASCVD were considered. The review includes interventions for weight loss, cardiometabolic and renal disease, blood pressure control, diet, and the occurrence of cardiovascular disease events. A few studies considered both primary and secondary prevention populations. The review is not exhaustive. We did not include studies that focused on heart failure or clinical presentations that may be difficult to classify, such as acute or chronic ischemic cardiovascular disease without myocardial infarction. Our purpose was to highlight recent research that will help the reader stay abreast of the changing field of cardiovascular prevention.

Parity and Risk of Cardiovascular Disease in Women over 45 Years in the United States: National Health and Nutrition Examination Survey 2007-2018.

Objective: Current research results on the association between parity and cardiovascular disease (CVD) risk are inconclusive. The purpose of this study was to examine the relationship between parity and risk of CVD in women over 45 years of age. Materials and Methods: Data were from the National Health and Nutrition Examination Survey for 2007-2018. A total of 8,882 women ≥45 years of age were included. The exposure of parity referred to the number of live births, and the outcome variable was the occurrence of CVD events, including stroke, heart attack, coronary heart disease (CHD), heart failure, and angina. We performed logistic regression to calculate the unadjusted and adjusted odds ratios (ORs; 95% confidence intervals [CIs]) controlling for confounding factors. Results: Among 8,882 women, the mean age was 62.4 ± 10.8 years, with a range of 45 to 80 years. The weighted prevalence of CVD, stroke, heart attack, CHD, heart failure, and angina in parous women were significantly higher than those of nulliparous women (p < 0.05). After adjusting for demographic factors, CVD risk factors, reproductive factors, the ORs of CVD with parity 1-2, 3-4, and 5+ were 1.85 (95% CI: 1.29-2.64), 1.70 (95% CI: 1.15-2.50), and 1.92 (95% CI: 1.28-2.88), respectively. The odds of stroke and heart attack were also significantly positively related to increasing parity compared with nulliparity. However, compared with nulliparity, parity of 3 was associated with a slightly lower risk of CVD. Conclusions: Our findings indicated that parity was significantly positively associated with CVD, giving birth to three children associated with a slightly lower risk compared with nulliparity. Further cohort studies are warranted to confirm the findings.

Metabolic Dysfunction-Associated Fatty Liver Disease Is Associated with the Risk of Incident Cardiovascular Disease: A Prospective Cohort Study in Xinjiang.

In 2020, a group of international experts proposed a new term ‘metabolic dysfunction-associated fatty liver disease’ (MAFLD) to replace ‘non-alcoholic fatty liver disease’. This study aimed to describe the epidemic characteristics of MAFLD, incidence of cardiovascular disease (CVD), and relationship between MAFLD and incident CVD. In 2016, 12,794 Uyghur adults from Kashgar, Xinjiang, were grouped according to the presence or absence of MAFLD. The primary outcome was the occurrence of CVD events. Fatty liver was diagnosed using ultrasound. The prevalence of MAFLD was 16.55%. After excluding patients with previous CVD, 11,444 participants were followed up for a median period of 4.7 years. During the follow-up period, the overall CVD incidence was 10.40% (1190/11,444). The incidence of CVD in the patients with MAFLD was significantly higher than that in the non-MAFLD patients (18.38% vs. 9.02%, p < 0.001; multivariable-adjusted hazard ratio = 1.37, 95% CI = 1.20–1.56). The prevalence of MAFLD was relatively low, whereas the incidence of CVD was relatively high among the Uyghur adults in rural Xinjiang. Individuals with MAFLD have a higher risk of developing CVD independent of traditional cardiovascular risk factors, obesity, type 2 diabetes mellitus (T2DM), and dyslipidaemia.

Cardiovascular disease events within 5\u2009years after a diagnosis of breast cancer

BackgroundConcern for cardiovascular disease (particularly atrial fibrillation-AF) among women with breast cancer is becoming a major issue. We aimed at determining the incidence of cardiovascular disease events (AF, arterial and cardiac events, venous-thromboembolism-VTE) in patients diagnosed with breast cancer, and assessing potential risk factors.MethodsWe reviewed medical records of all patients diagnosed with breast cancer from 2010 to 2011 in our cancer center. Baseline characteristics of patients and tumors were collected. The main outcome was the occurrence of cardiovascular disease events (AF, VTE, arterial and cardiac events) during the 5-years follow-up.ResultsAmong the 682 breast cancer patients, 22 (3.2%) patients had a history of atrial fibrillation. Thirty-four patients (5%) presented at least one cardiovascular disease event, leading to a cumulative incidence of 5.8% events at 5-years ([3.8–7.7] CI 95%), with most of them occurring in the first 2 years. AF cumulative incidence was 1.1% ([0.1–2.1] CI 95%). Factors associated with the occurrence of cardiovascular disease events (including AF) were an overexpression of HER-2 (HR 2.6 [1.21–5.56] p < 0.011), UICC-stage III tumors or more (HR 5.47 [2.78–10.76] p < 0.001) and pre-existing cardiovascular risk factors (HR 2.91 [1.36–6.23] p < 0.004).ConclusionThe incidence of cardiovascular disease events was 5.8% ([3.8–7.7] CI 95%), with HER-2 over-expression, UICC-stage III tumors or more and pre-existing cardiovascular diseases being associated with them. These findings call for the development of preventive strategies in patients diagnosed with breast cancer.

Kidney dysfunction is associated with risk of cardiovascular events in middle-aged and elderly population with hypertension: A5-yearcommunity-based cohort study in China .

To evaluate the association between kidney dysfunction and cardiovascular disease (CVD) events in a middle-aged and elderly population in China. In July 2009, a baseline survey of health status was performed in adults aged 55 years and older from Beijing, China. Occurrence of CVD events and mortality in subjects free of CVD at baseline was recorded in a 5-year follow-up period until December 2014. The association of mild (eGFRCKD-EPI 45 - 59 mL/min/1.73m2) and moderate to severe (eGFRCKD-EPI < 45 mL/min/1.73m2) kidney dysfunction with adverse outcomes were analyzed with Cox regression analysis. A total of 1,257 subjects were included in the final analysis. The risk of CVD events in those with mild kidney dysfunction increased by 65% (HR: 1.65, 95% CI: 1.04-2.62) as compared to those with normal kidney function. Subjects with both hypertension and CKD experienced more significantly increased risk of CVD events (adjusted HR = 1.87, 95% CI 1.17-2.97) and stroke (adjusted HR = 2.24, 95% CI 1.24-4.04). Pulse pressure (PP) ≥60 mmHg was the strongest risk factor for stroke in patients with CKD, with the adjusted HR value of 1.98 (95% CI 1.08-3.64). Moderate to severe kidney dysfunction was an independent risk predictor of CVD events. Among subjects with hypertension or poorly controlled blood pressure level, the presence of CKD significantly increased the risks of CVD events and stroke.

Entropy-Based Measures of Hypnopompic Heart Rate Variability Contribute to the Automatic Prediction of Cardiovascular Events.

Surges in sympathetic activity should be a major contributor to the frequent occurrence of cardiovascular events towards the end of nocturnal sleep. We aimed to investigate whether the analysis of hypnopompic heart rate variability (HRV) could assist in the prediction of cardiovascular disease (CVD). 2217 baseline CVD-free subjects were identified and divided into CVD group and non-CVD group, according to the presence of CVD during a follow-up visit. HRV measures derived from time domain analysis, frequency domain analysis and nonlinear analysis were employed to characterize cardiac functioning. Machine learning models for both long-term and short-term CVD prediction were then constructed, based on hypnopompic HRV metrics and other typical CVD risk factors. CVD was associated with significant alterations in hypnopompic HRV. An accuracy of 81.4% was achieved in short-term prediction of CVD, demonstrating a 10.7% increase compared with long-term prediction. There was a decline of more than 6% in the predictive performance of short-term CVD outcomes without HRV metrics. The complexity of hypnopompic HRV, measured by entropy-based indices, contributed considerably to the prediction and achieved greater importance in the proposed models than conventional HRV measures. Our findings suggest that Hypnopompic HRV assists the prediction of CVD outcomes, especially the occurrence of CVD event within two years.

Undertreatment of hypertension and hypercholesterolaemia in children and adolescents with type 1 diabetes: long-term follow-up on time trends in the occurrence of cardiovascular disease, risk factors and medications use.

The aims of the present study were, firstly, to evaluate long-term trends in the occurrence and treatment of cardiovascular disease (CVD) risk factors and the occurrence of CVD events in children with type 1 diabetes mellitus (T1DM) and, secondly, to assess the determinants of undertreatment of CVD risk factors. A retrospective cohort study was conducted in 3728 children (<19years of age) with T1DM and up to 5 age- and gender-matched diabetes-free children (reference cohort) (n=18 513) using data from the Clinical Practice Research Datalink (CPRD). Compared with diabetes-free subjects, children with T1DM had significantly higher annual prevalence rates of CVD risk factors and cardiovascular (CV) medication use 20years after the onset of diabetes (index date): hypertension: 35.2% vs. 11.4%, P < 0.001; hypercholesterolaemia: 66.7% vs. 7.14%, P<0.001; and CV medication use: 37.0% vs. 3.6%, P < 0.001. The significant differences between prevalence rates in the two cohorts started from 1year before the index date. Furthermore, 50% of the children in the T1DM cohort with hypertension and 53% with hypercholesterolaemia remained untreated with CV drugs for a period of 2-5years during the 20-year follow-up. Age was the only determinant associated with undertreated hypertension in the T1DM cohort. Children with T1DM had substantially higher prevalence rates of hypertension and hypercholesterolaemia from 1year before up to 20years after the onset of diabetes compared with nondiabetics. There is a substantial undertreatment of CVD risk factors with CV drugs. In children with T1DM, screening for CVD risk factors and adequate treatment are of the utmost importance to prevent CVD later in life.

Cardiovascular disease in familial hypercholesterolemia: Validation and refinement of the Montreal-FH-SCORE

Familial hypercholesterolemia (FH) is a disease characterized by increased low-density lipoprotein cholesterol and premature cardiovascular disease (CVD) but there is marked individuality in the occurrence of CVD events. Recently, the Montreal-FH-SCORE (MFHS) has been shown to stratify CVD frequency in FH subjects, but this score has not yet been validated. The aims of the present study were to conduct an independent external validation of the MFHS in a retrospective cohort of heterozygous FH and to identify additional variables that could significantly improve the prediction of prevalent CVD. The MFHS calculation is based on 5 variables: age, high-density lipoprotein cholesterol, gender, hypertension, and smoking status. This score was validated in a cohort of 718 adult FH using receiver operating characteristic (ROC) curves analysis to determine the discriminatory ability of the MFHS. The performance of the MFHS was compared to a novel Combined-FH-SCORE in 1388 FH. The MFHS had an excellent discrimination for prevalent CVD events in the validation cohort, with an area under the receiver operating characteristic curve of 0.799 (0.766-0.832, P<.0001). Patients with a high MFHS score presented a significant 8.8-fold increased odd of CVD events compared with patients with a low score (95% confidence interval 5.8-13.3, P<.0001). The addition of lipoprotein(a) to the score did not improve the prediction of CVD events (area under the receiver operating characteristic curve 0.823 vs 0.817, P=.11). This study confirmed that the MFHS is a strong predictor of prevalent CVD in FH and that the addition of lipoprotein(a) offers a minor improvement in the discrimination of the score.

Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies.

Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (P<1.08E-07) and replicated 33 (at Bonferroni-corrected P<0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglycerides and high-density lipoprotein cholesterol (HDL-C; cg27243685; P=8.1E-26 and 9.3E-19) was associated with cis-expression of a reverse cholesterol transporter (ABCG1; P=7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P=0.0007). We found significant cis-methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels (PTC=0.004, PHDL-C=0.008 and Ptriglycerides=0.00003) and coronary heart disease (P=0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis-methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events.

Predictive Value of Arterial Stiffness and Subclinical Carotid Atherosclerosis for Cardiovascular Disease in Patients with Rheumatoid Arthritis

We evaluated the predictive value of these vascular biomarkers for cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA): aortic pulse wave velocity (aPWV), augmentation index (AIx), carotid intima-media thickness (cIMT), and carotid plaques (CP). They are often used as risk markers for CVD. In 2007, 138 patients with RA underwent clinical examination, laboratory tests, blood pressure testing, and vascular biomarker measurements. Occurrence of CVD events was recorded in 2013. Predictive values were assessed in Kaplan-Meier plots, log-rank, and crude and adjusted Cox proportional hazard (PH) regression analyses. Baseline median age and disease duration was 59.0 years and 17.0 years, respectively, and 76.1% were women. CVD events occurred in 10 patients (7.2%) during a mean followup of 5.4 years. Compared with patients with low aPWV, AIx, cIMT, and without CP, patients with high aPWV (p < 0.001), high AIx (p = 0.04), high cIMT (p = 0.01), and CP (p < 0.005) at baseline experienced more CVD events. In crude Cox PH regression analyses, aPWV (p < 0.001), cIMT (p < 0.001), age (p = 0.01), statin (p = 0.01), and corticosteroid use (p = 0.01) were predictive of CVD events, while AIx was nonsignificant (p = 0.19). The Cox PH regression estimates for vascular biomarkers were not significantly altered when adjusting individually for demographic variables, traditional CVD risk factors, RA disease-related variables, or medication. All patients who developed CVD had CP at baseline. CP, aPWV, and cIMT were predictive of CVD events in this cohort of patients with RA. Future studies are warranted to examine the additive value of arterial stiffness and carotid atherosclerosis markers in CVD risk algorithms. Regional Ethical Committee approval numbers 2009/1582 and 2009/1583.

Design of and rationale for the Japan Diabetes Optimal Integrated Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3): a multicenter, open-label, randomized, parallel-group trial

ObjectiveMultifactorial intervention including the management of levels of blood glucose (BG), blood pressure (BP), and lipids has been suggested to decrease cardiovascular disease (CVD) risk. However, the target ideal and...

PCSK9 inhibitors.

The discovery of proprotein convertase subtilisin kexin 9 (PCSK9) has considerably changed the therapeutic options in the field of lipid management. PCSK9 reduces LDL receptor recycling, leading to a decrease of low-density lipoprotein cholesterol (LDL-C) receptors on the surface of hepatocytes and a subsequent increase of circulating LDL-C levels. In observational studies, the loss-of-function mutations of PCSK9 have been associated with a reduction of LDL-C levels and cardiovascular disease (CVD) events. In contrast, humans with high levels of PCSK9 have higher level of plasma LDL-C and significantly enhanced CVD risk during their lifetime, gain-of-function mutations on PCSK9 are, for instance, causatively associated with familial hypercholesterolaemia (FH). Inhibition of PCSK9 is therefore a promising therapeutic option for the lowering of LDL-C levels. The clinical development of human monoclonal antibodies against PCSK9 has progressed, with promising results reported from phase 2 clinical studies in patients with FH or intolerant to statin with LDL-C levels not on target levels. Phase I studies demonstrated safety and efficacy. In phase II, a 60%-70% reduction in LDL-C was observed, especially when subcutaneous injections were performed regularly every two weeks. No significant side effects were observed, with the exception of injection site reactions. Three large phase III programmes with the new anti PCSK9 antibodies are currently underway in patients with acute coronary syndrome (ACS) and LDL-C inadequately controlled by standard treatments. The main objective of these studies is to evaluate the effect of PCSK9 inhibition on the occurrence of CVD events in patients with ACS.

Serial assessment of arterial stiffness by cardio-ankle vascular index for prediction of future cardiovascular events in patients with coronary artery disease

Purpose: Arterial stiffness is a significant predictor of cardiovascular disease (CVD), which is modified by medications for atherosclerotic risk factors and life-style changes. Cardio-ankle vascular index (CAVI) provides noninvasive, objective information on arterial stiffness, independent of blood pressure. This study aimed to investigate changes in CAVI after management of atherosclerotic risk factors and their impact on future CVD outcome in patients with coronary artery disease (CAD). Methods: The study consisted of 211 CAD patients (65±10 years, 118 men) with impaired CAVI. CAVI examination was repeated 6 months later. Impaired CAVI was defined as > the mean plus 1 SD of the age- and gender-specific normal CAVI values, according to the results in 5,188 healthy subjects. All patients were followed for more than 1 year or until the occurrence of CVD event. Results: Of the 211 patients, CAVI improved 6 months later in 106 (50%) patients, but remained high in 105 (50%) patients. During follow-up (2.9±1.0 years), CVD events occurred in 28 (13%) patients. Persistently impaired CAVI was an independent predictor of future CVD events (p=0.003), independent of baseline CAVI. The CVD outcome was worse in patients with persistently impaired CAVI than in those with improved CAVI (p<0.001) (Figure). Patients with normalized CAVI after treatment (n=22) had only 1 CVD event. ![Figure][1] Kaplan-Meier curves for CVD events Conclusions: This study demonstrated for the first time that persistent impairment of arterial stiffness was an independent risk factor of future CVD events. Serial measurement of CAVI provides important prognostic information on patients with CAD in clinical practice. [1]: pending:yes

Association Between Abacavir Exposure and Increased Risk for Cardiovascular Disease in Patients with Human Immunodeficiency Virus

Human immunodeficiency virus (HIV) infection and the receipt of antiretroviral therapy have been associated with the development of cardiovascular disease. The occurrence of cardiovascular events in HIV-infected patients has often been associated with treatment-induced dyslipidemia, insulin resistance, and body composition changes. These treatment-related complications are often the result of exposures to protease inhibitors or thymidine analogs such as stavudine or zidovudine. Recent investigations, however, have suggested an association between exposure to the nucleoside reverse transcriptase inhibitor, abacavir, and the occurrence of cardiovascular disease events. Based on these findings, current guidelines recommend using caution in patients receiving abacavir who are at a high risk for cardiovascular disease. Decisions to replace abacavir in a patient's regimen should be considered on an individual basis and with complete evaluation of the associated benefits and risks. Furthermore, additional studies are necessary to definitively determine the association between abacavir exposure and the occurrence of cardiovascular disease events. Studies are also necessary to definitively identify the contributions of both HIV infection and individual antiretroviral agents on the development of cardiovascular disease.

Variation at the paraoxonase gene locus contributes to carotid arterial wall thickness in subjects with familial hypercholesterolemia

Objectives: Paraoxonase (PON1) is a potent enzyme, physically associated with the high-density lipoprotein particle. PON1 may protect against cardiovascular disease (CVD), since it is capable of hydrolyzing oxidized LDL-cholesterol, thereby negating the detrimental effects of this lipoprotein on the arterial wall. Design and methods: In 187 patients with familial hypercholesterolemia, we studied the seven most common single nucleotide polymorphisms (SNPs) in both the coding and promoter sequences of PON1 (L55M, Q192R, T-107C, C-126G, G-162A, G-824A, and C-907G) in terms of PON1 activity and intima media thickness (IMT) of the carotid arterial wall, a validated surrogate marker for CVD. Results: In concordance with several previous studies, we observed that the L55M, T-107C, G-162A, G-824A, and C-907G SNPs conferred PON1 activity towards phenylacetate, while this was not the case for the Q192R and C-126G SNPs. Importantly, in a multivariate regression analysis, G-824A proved to be an independent predictor of carotid IMT. Additionally, the two fully discordant homozygous haplotypes, C-907/G-824/G-162/C-126/T-107/55M versus -907G/-824A/-162A/-126G/-107C/L55, differed by 22% in carotid IMT ( P = 0.007). Conclusions: Genetic variation at the PON1 locus has a strong influence on PON1 activity as well as on carotid IMT. These data indicate that PON1 is indeed involved in the pathogenesis of atherosclerosis. Whether this also translates into a role for PON1 in the occurrence of CVD events needs to be confirmed by large prospective studies in the general population.