Burden Of Atherosclerotic Cardiovascular Disease Research Articles

Impact of Non-Pharmacological Interventions on the Mechanisms of Atherosclerosis.

Atherosclerosis remains the leading cause of mortality and morbidity worldwide characterized by the deposition of lipids and fibrous elements in the form of atheroma plaques in vascular areas which are hemodynamically overloaded. The global burden of atherosclerotic cardiovascular disease is steadily increasing and is considered the largest known non-infectious pandemic. The management of atherosclerotic cardiovascular disease is increasing the cost of health care worldwide, which is a concern for researchers and physicians and has caused them to strive to find effective long-term strategies to improve the efficiency of treatments by managing conventional risk factors. Primary prevention of atherosclerotic cardiovascular disease is the preferred method to reduce cardiovascular risk. Fasting, a Mediterranean diet, and caloric restriction can be considered useful clinical tools. The protective impact of physical exercise over the cardiovascular system has been studied in recent years with the intention of explaining the mechanisms involved; the increase in heat shock proteins, antioxidant enzymes and regulators of cardiac myocyte proliferation concentration seem to be the molecular and biochemical shifts that are involved. Developing new therapeutic strategies such as vagus nerve stimulation, either to prevent or slow the disease’s onset and progression, will surely have a profound effect on the lives of millions of people.

A Clinically Validated Genetic Screening for Familial Hypercholesterolemia in Quebec

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis Familial Hypercholesterolemia (FH) is the most common genetic disorder in humans with an estimated prevalence of 1/311. In geographic regions with founder effect mutations, such as the province of Quebec, Canada, prevalence is as high as 1/80. FH is associated with premature atherosclerotic cardiovascular disease (ASCVD) caused by elevated low-density lipoprotein cholesterol (LDL-C). Although early diagnosis and therapy of FH can normalize life expectancy, less than 15% of cases are diagnosed. Cascade screening and genetic testing aim to improve diagnosis, treatment, and outcomes in FH. Objective/Purpose Determine the impact of unbiased genetic testing in re-classification of patients with a clinical diagnosis of FH in Quebec, in comparison with the existing genetic panel offered by Quebec's Ministry of Health and Social Services (Ministere de la Sante et des Services Sociaux (MSSS)). Methods A retrospective cohort study was conducted on patients seen in the Preventive Cardiology/Lipid Clinic of the McGill University Health Center (MUHC) at the Royal Victoria Hospital in Montreal, Quebec, Canada, between September 2017 to September 2021. The MUHC Preventive Cardiology/Lipid clinic is one of the 19 academic FH Canada Registry participating sites. Here, we report a single-center experience with the only clinically validated molecular genetic screening for FH (CLIA compliant) in Canada. We performed next-generation sequencing of the LDLR, APOB, and PCSK9 genes and multiplex ligation-dependent probe amplification (MLPA) of the LDLR gene to detect genetic mutations and copy number variants. All mutations were reviewed by a geneticist and cross-referenced in ClinVar. Results Between 2018-2021, we examined 369 FH cases (57% males, 43% females) based on the Canadian FH definition clinical criteria. For index patients, mean age at diagnosis was 40+/- 16 years, while 30+/-16 years was for cascade screening patients. Baseline (untreated) LDL-C was 6.5+/-2.0 mmol/L. In 224 patients who underwent genetic testing, a pathogenic mutation was identified in 167 (75%) individuals, in keeping with ∼20% of FH patients with a polygenic form. A majority of affected patients had mutations in the LDLR (87%) or APOB (13%) genes. Interestingly, the genetic panel offered by Quebec's Health Ministry, which includes 10 common mutations in French Canadians, only accounted for 46% of identified mutations. Even in patients self-describing as French Canadians, more than 20% did not have a common mutation. We subsequently examined the impact of genetic testing in re-classification of patients' FH diagnosis. Interestingly, genetic screening identified a genetic variant in 26% of patients initially classified as 'severe hypercholesterolemia' and allowed for 85 (75%) of patients initially diagnosed as 'probable FH' to be re-classified as 'definite FH'. Conclusions Genetic testing in patients suspected of having FH provides diagnostic certainty and permits re-classification of individuals with a diagnosis of 'severe hypercholesterolemia' or 'probable FH' according to current definitions. Furthermore, the limited genetic panel offered by the province of Quebec, focusing on common French-Canadian mutations, provides incomplete data in the majority of cases. We therefore propose that most patients with a presumptive diagnosis of FH undergo an unbiased genetic analysis. This allows for increased identification of FH patients and can help reduce burden of ASCVD and death in Canadians with FH. Furthermore, this study has important implications on cascade screening, public health policies and reimbursement of drugs such as PCSK9 inhibitors. Nothing to disclose.

Atherosclerotic cardiovascular disease burden in patients with familial hypercholesterolemia: interpretation of data on involvement of different vascular beds.

Familial hypercholesterolemia (FH) is a monogenic, autosomal dominant disorder that results in a rise of low‑density lipoprotein cholesterol (LDL‑C) and markedly increased risk of premature atherosclerotic cardiovascular disease. FH is relatively common, treatable, and its clinical course can be improved through early detection and timely initiation of lipid‑lowering medications. The clinical picture of FH is highly variable, with a heterogeneous phenotype even within a single family, ranging from patients with very early onset of major cardiovascular events to those who do not develop overt cardiovascular disease even at an old age. We summarized studies indicating that atherosclerotic involvement in the coronary arteries and lower extremities is higher in FH patients than in the general population. There is a paucity of data regarding the relationship between FH and the incidence of atherosclerosis in other vascular beds. There are no studies systematically evaluating several vascular beds in asymptomatic patients with FH. Providing a systematic characteristic of patients with FH with respect to the presence and extent of atherosclerotic lesions in different vascular beds may have implications for daily practice not only for patients with FH but also for a larger number of patients with very high plasma LDL‑C concentrations.

Temporal Trends in the Remaining Lifetime Risk of Cardiovascular Disease Among Middle-Aged Adults Across 6 Decades: The Framingham Study.

The remaining lifetime risk (RLR) is the probability of developing an outcome over the remainder of one's lifespan at any given age. The RLR for atherosclerotic cardiovascular disease (ASCVD) in three 20-year periods were assessed using data from a single community-based cohort study of predominantly White participants. Longitudinal data from the Framingham study in 3 epochs (epoch 1, 1960-1979; epoch 2, 1980-1999; epoch 3, 2000-2018) were evaluated. The RLR of a first ASCVD event (myocardial infarction, coronary heart disease death, or stroke) from 45 years of age (adjusting for competing risk of death) in the 3 epochs were compared overall, and according to the following strata: sex, body mass index, blood pressure and cholesterol categories, diabetes, smoking, and Framingham risk score groups. There were 317 849 person-years of observations during the 3 epochs (56% women; 94% White) and 4855 deaths occurred. Life expectancy rose by 10.1 years (men) to 11.9 years (women) across the 3 epochs. There were 1085 ASCVD events over the course of 91 330 person-years in epoch 1, 1330 ASCVD events over the course of 107 450 person-years in epoch 2, and 775 ASCVD events over the course of 119 069 person-years in epoch 3. The mean age at onset of first ASCVD event was greater in the third epoch by 8.1 years (men) to 10.3 years (women) compared with the first epoch. The RLR of ASCVD from 45 years of age declined from 43.7% in epoch 1 to 28.1% in epoch 3 (P<0.0001), a finding that was consistent in both sexes (RLR [epoch 1 versus epoch 3], 36.3% versus 26.5% [women]; 52.5% versus 30.1% [men]; P<0.001 for both). The lower RLR of ASCVD in the last 2 epochs was observed consistently across body mass index, blood pressure, cholesterol, diabetes, smoking, and Framingham risk score strata (P<0.001 for all). The RLR of coronary heart disease events and stroke declined in both sexes (P<0.001). Over the past 6 decades, mean life expectancy increased and the RLR of ASCVD decreased in the community-based, predominantly White Framingham study. The residual burden of ASCVD underscores the importance of continued and effective primary prevention efforts with better screening for risk factors and their effective treatment.

Chinese expert consensus on non-traditional blood lipid parameters to control the risks of arteriosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease is the general name of a series of diseases based on atherosclerosis. With the development of the social economy and the progress of population aging in China, the burden of atherosclerotic cardiovascular disease is increasing. However, in recent years some clinical studies have proved that the traditional blood lipid indicators, including low-density lipoprotein cholesterol, have some limitations in the risk control of atherosclerotic cardiovascular disease, and the blood lipid indicators need to be further supplemented and improved. This consensus expounds non-traditional blood lipid indexes from the perspectives of test and clinic, mainly including apolipoprotein B and lipoprotein a, non-high density lipoprotein cholesterol and lipoprotein residue, and non-fasting blood lipid. This consensus systematically expounds the pathophysiological mechanism of non-traditional blood lipid indexes, the relationship with cardiovascular disease, detection methods and performance, intervention, control and application in the state of cardiovascular disease, and gives the corresponding clinical expert suggestion.

A community based cross sectional study on the prevalence of dyslipidemias and 10\xa0years cardiovascular risk scores in adults in Asmara, Eritrea

Despite the contribution of dyslipidemia to the high and rising burden of arteriosclerotic cardiovascular disease (CVD) in Sub-Saharan Africa; the condition is under-diagnosed, under-treated, and under-described. The objective of this study was to explore the prevalence of dyslipidemias, estimate a 10-year cardiovascular disease risk and associated factors in adults (≥ 35 to ≤ 85 years) living in Asmara, Eritrea. This population-based cross-sectional study was conducted among individuals without overt CVDs in Asmara, Eritrea, from October 2020 to November 2020. After stratified multistage sampling, a total of 386 (144 (37%) males and 242 (63%) females, mean age ± SD, 52.17 ± 13.29 years) respondents were randomly selected. The WHO NCD STEPS instrument version 3.1 questionnaire was used to collect data. Information on socio-demographic variables was collected via interviews by trained data collectors. Measurements/or analyses including anthropometric, lipid panel, fasting plasma glucose, and blood pressure were also undertaken. Finally, data was analyzed by using Statistical Package for Social Sciences version 26.0 for Windows (SPSS Inc., Chicago, IL, USA). All p-values were 2-sided and the level of significance was set at p < 0.05 for all analyses. The frequency of dyslipidemia in this population was disproportionately high (87.4%) with the worst affected subgroup in the 51–60 age band. Further, 98% of the study participants were not aware of their diagnosis. In terms of individual lipid markers, the proportions were as follows: low HDL-C (55.2%); high TC (49.7%); high LDL (44.8%); high TG (38.1%). The mean ± SD, for HDL-C, TC, LDL-C, non-HDL-C, and TG were 45.28 ± 9.60; 205.24 ± 45.77; 130.77 ± 36.15; 160.22 ± 42.09 and 144.5 ± 61.26 mg/dL, respectively. Regarding NCEP ATP III risk criteria, 17.6%, 19.4%, 16.3%, 19.7%, and 54.7% were in high or very high-risk categories for TC, Non-HDL-C, TG, LDL-C, and HDL-C, respectively. Among all respondents, 59.6% had mixed dyslipidemias with TC + TG + LDL-C dominating. In addition, 27.3%, 28.04%, 23.0%, and 8.6% had abnormalities in 1, 2, 3 and 4 lipid abnormalities, respectively. Multivariate logistic regression modeling suggested that dyslipidemia was lower in subjects who were employed (aOR 0.48, 95% CI 0.24–0.97, p = 0.015); self-employed (aOR 0.41, 95% CI 0.17–1.00, p = 0.018); and married (aOR 2.35, 95% CI 1.19–4.66, p = 0.009). A higher likelihood of dyslipidemia was also associated with increasing DBP (aOR 1.04 mmHg (1.00–1.09, p = 0.001) and increasing FPG (aOR 1.02 per 1 mg/dL, 95% CI 1.00–1.05, p = 0.001). Separately, Framingham CVD Risk score estimates suggested that 12.7% and 2.8% were at 10 years CVD high risk or very high-risk strata. High frequency of poor lipid health may be a prominent contributor to the high burden of atherosclerotic CVDs—related mortality and morbidity in Asmara, Eritrea. Consequently, efforts directed at early detection, and evidence-based interventions are warranted. The low awareness rate also points at education within the population as a possible intervention pathway.

Familial hypercholesterolemia in China requires greater efforts

Familial hypercholesterolemia in China requires greater efforts

Atherosclerotic Cardiovascular Disease Risk and Lipid-Lowering Therapy Requirement in China

BackgroundLipid-lowering therapy (LLT) is one of the key strategies for reducing the atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the percentage of people in need of different LLT regimens to achieve optimal targets of low-density lipoprotein cholesterol (LDL-C), and the corresponding cost and benefit.MethodsWe conducted a simulation study based on the data from the nationwide China PEACE MPP population cohort (2015–2020), from which we included 2,904,914 participants aged 35–75 years from all the 31 provinces in mainland China. Participants were grouped based on their 10-year ASCVD risks, then entered into a Monte Carlo model which was used to perform LLT intensification simulation scenarios to achieve corresponding LDL-C goals in each risk stratification.ResultsAfter standardizing age and sex, the proportions of participants included at low, moderate, high, and very-high risk were 70.8%, 15.6%, 11.5%, and 2.1%, respectively. People who failed to achieve the corresponding LDL-C goals −8.1% at low risk, 19.6% at moderate risk, 53.2% at high risk, and 93.6% at very-high risk (either not achieving the goal or not receiving LLT)—would be in need of the LLT intensification simulation. After the use of atorvastatin 20 mg was simulated, over 99% of the population at low or moderate risk could achieve the LDL-C goals; while 11.3% at high and 24.5% at very-high risk would still require additional non-statin therapy. After the additional use of ezetimibe, there were still 4.8% at high risk and 11.3% at very-high risk in need of evolocumab; and 99% of these two groups could achieve the LDL-C goals after the use of evolocumab. Such LLT intensification with statin, ezetimibe, and evolocumab would annually cost $2.4 billion, $4.2 billion, and $24.5 billion, respectively, and prevent 264,170, 18,390, and 17,045 cardiovascular events, respectively.ConclusionsModerate-intensity statin therapy is pivotal for the attainment of optimal LDL-C goals in China, and around 10–25% of high- or very-high-risk patients would require additional non-statin agents. There is an opportunity to reduce the rising ASCVD burden in China by optimizing LLT.

Cardiovascular risk profile of Middle Eastern immigrants living in the United States-the National Health Interview Survey

BackgroundMiddle Eastern (ME) immigrants are one of the fastest-growing groups in the US. Although ME countries have a high burden of atherosclerotic cardiovascular disease (ASCVD), the cardiovascular health status among ME immigrants in the US has not been studied in detail. This study aims to characterize the cardiovascular health status (CVD risk factors and ASCVD burden) among ME immigrants in the US. MethodsWe used 2012–2018 data from the National Health Interview Survey, a US nationally representative survey. ME origin, CVD risk factors, and ASCVD status were self-reported. We compared these to US-born non-Hispanic white (NHW) individuals in the US. ResultsAmong 139,778 adults included, 886 (representing 1.3 million individuals, mean age 46.8) were of ME origin, and 138,892 were US-born NHWs (representing 150 million US adults, mean age 49.3). ME participants were more likely to have higher education, lower income and be uninsured. The age-adjusted prevalence of hypertension (22.4% vs 27.4%) and obesity (21.4% vs 31.4%) were significantly lower in ME vs NHW participants, respectively. There were no significant differences between the groups in the age-adjusted prevalence of ASCVD, diabetes, hyperlipidemia, and smoking. Only insufficient physical activity was higher among ME individuals. ME immigrants living in the US for 10 years or more reported higher age-adjusted prevalence of hypertension, hyperlipidemia, and ASCVD. ConclusionsME immigrants in the US have lower odds of hypertension and obesity, and of having a suboptimal CRF profile compared to US-born NHWs. Further studies are needed to determine whether these findings are related to lower risk, selection of a healthier ME subgroup in NHIS, or possible under-detection of cardiovascular risk factors in ME immigrants living in the US.

Improvement of evaluation in Chinese patients with atherosclerotic cardiovascular disease using the very-high-risk refinement: a population-based study

BackgroundContinuous refinement of atherosclerotic cardiovascular disease (ASCVD) stratification has raised the definition of very-high-risk (VHR) recently, which has been underutilized in China. We aimed to identify patients at VHR and evaluate their performances in a Chinese population. MethodsA total of 9944 patients with ASCVD was continuously enrolled. Patients at VHR was identified according to 2018 AHA/ACC guideline. Median follow-up was 36.4 months. Clinical characteristics, low-density lipoprotein cholesterol (LDL-C) achievements, and the prognostic value of VHR mapping for cardiovascular events (CVEs) were evaluated. FindingsOverall, 26% (2542/9944) of patients were deemed as VHR, which were subsequently divided into two subgroups of VHR-1 [31% (779/2542)] and VHR-2 [69% (1763/2542)]. The rates of VHR were higher among patients of male (30%,2157/7268), young with age <45 years (46%,518/1130), and low-income regions (27%, 498/1838). Patients at VHR carried higher rates of risk factors than those at non-VHR (all p<0.001). However, only 3% (80/2542) of patients at VHR were prescribed with high-intensity of statins, and just 13% (321/2542) of them reached the LDL-C goal (<1.4mmol/L). Furthermore, of patients with coronary stenosis (n=9806), multiple-diseased vessels (47%, 1192/2523 vs. 36%,2587/7283) and occlusive lesions (36%, 902/2523 vs. 13%, 949/7283) were detected more commonly in those at VHR than non-VHR. The adjusted hazard ratios of VHR-1 and VHR-2 for primary CVEs were 2.58(1.61-4.14) and 2.23(1.55-3.20), respectively. InterpretationOur study firstly reported that patients at VHR carried more severe ASCVD burden, lower LDL-C achievement, and higher CVEs risk, suggesting that the refinement of ASCVD might be considered in China to further understand patients at VHR. FundingCapital Health Development Fund and CAMS Major Collaborative Innovation Project

Cardiovascular risk assessment in people living with HIV compared to the general population

Abstract Background Effective cardiovascular preventive strategies are crucial among people living with HIV (PLWH), who are facing a high burden of atherosclerotic cardiovascular disease (ASCVD). However, it remains unclear which cardiovascular risk score is the most appropriate in clinical practice. Purpose We aimed to prospectively assess and compare the accuracy of widely used cardiovascular risk scores in PLWH and individuals from the general population. Methods We used data from the Swiss HIV Cohort Study (SHCS), a longitudinal study involving 20,802 HIV-infected adults aged over 18 years, and from the CoLaus|PsyCoLaus study, a Swiss population-based cohort including 6,733 individuals aged 35–75 years. The European Systematic Coronary Risk Evaluation Score (SCORE), the North American Pooled Cohort Equation (PCE) and the HIV-specific Data Collection o-n Adverse events of Anti-HIV Drugs (D:A:D) score were calculated for all participants free from ASCVD between January 1, 2003 and December 31, 2009. Accuracy of the scores was assessed based on discrimination and calibration metrics for each cohort separately using incident ASCVD as outcome. The value of adding HIV-specific factors to the model presenting the best predictive capacities between SCORE and PCE was evaluated using the net reclassification index (NRI). Results 6,373 PLWH (28.4% women; aged 40.6 [SD, 9.9]; 57.2% on antiretroviral therapy) and 5,403 individuals from the general population (53.5% women, aged 52.8 [SD, 10.7]) were included in the analysis with a mean follow-up time of 13.5 (SD, 4.1) and 9.9 (SD, 2.3) years, respectively. 533 (8.4%) participants in the SHCS and 374 (6.9%) in the CoLaus|PsyCoLaus study experienced an incident ASCVD translating into age-adjusted incidence rates of 12.9 vs. 7.5 per 1,000 person-year, respectively. In SHCS, PCE and D:A:D presented discriminative capacities with AUROC of 0.757 (95% CI, 0.736–0.777) and 0.763 (95% CI, 0.743–0.783), respectively, compared to SCORE (0.704 [95% CI, 0.681–0.728]). Calibration of all scores was suboptimal in SHCS, with under-prediction of ASCVD in the higher deciles of risk compared to the CoLaus|PsyCoLaus study. Adding CD4 nadir (&amp;lt;200 cells/mm3) and abacavir exposure as categorical variables to PCE resulted in a marginal improvement in discrimination and in a global NRI of 2.7% (95% CI, 0.3–5.1, p-value = 0.03). Conclusions PLWH presented a two-fold higher rate of incident ASCVD compared to individuals of the same age from the general population. The accuracy of PCE score to predict ASCVD in PLWH is equivalent to the D:A:D score and may represent a better alternative due to its reduced set of variables and its widespread use. Adding HIV-specific factors to PCE did not improve its predictive performance. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation

Trends in low-density lipoprotein cholesterol level among Chinese young adults hospitalized with first acute myocardial infarction.

BackgroundRepresentative data has shown a linear increase in mean low-density lipoprotein cholesterol (LDL-C) levels among Chinese adults, contributing to the burden of atherosclerotic cardiovascular disease (ASCVD). This study aimed to assess the trends in LDL-C levels and their association with coronary artery stenosis during the first acute myocardial infarction (AMI) in young Chinese adults.MethodsA retrospective study including 2,781 adults, aged 18–44 years, hospitalized for their first AMI in Beijing Anzhen hospital between 2007 and 2017 was performed.ResultsMean LDL-C level was 2.82±0.97 mmol/L with the prevalence of elevated LDL-C being 21.6% (601/2,781). Of the study, only 4.2% were aware of their elevated LDL-C status. Neither mean LDL-C concentration nor prevalence of elevated LDL-C showed a downward trend between 2007 and 2017 (P>0.05). Patients aged <35 years had the highest LDL-C level and frequency of elevated LDL-C among the three age groups (aged <35, 35–39, and 40–44 years; P<0.01). Patients with LDL-C ≥3.4 mmol/L evinced a more than 50% increased risk of coronary artery stenosis compared with those with LDL-C <1.4 mmol/L [adjusted odds ratio (OR) 3.19; 95% confidence interval (CI): 1.62 to 6.29]. Of the study, 62.0% had at least two conventional risk factors (RFs), and smoking, accompanied by hypertension, obesity, or elevated LDL-C were the most common combinations.ConclusionsThe current study provides an overview of trends in LDL-C level and elevated LDL-C among young adults at the time of first AMI. Patients had a high prevalence of elevated LDL-C but low awareness of this status. Coronary artery stenosis was positively correlated with LDL-C level. Preventive strategies, including public education regarding cholesterol levels and benefits of maintaining LDL-C below 3.4 mmol/L should be considered for young adults as a primary preventive strategy.

Genetic testing for familial hypercholesterolaemia

Familial hypercholesterolaemia (FH) is a codominant genetic disorder causing premature atherosclerotic cardiovascular disease (ASCVD). It is common, affecting 1 in 250 individuals worldwide and of the ∼100,000 Australians estimated to have FH, most are undiagnosed and treatment is often suboptimal. Several scoring algorithms based on low-density lipoprotein-cholesterol (LDL-C) levels, physical findings, and elements of personal and family history, help clinicians diagnose FH at varying levels of confidence ranging from possible to definite. Targeted DNA sequencing to identify the underlying pathogenic variant in any of the three FH genes (LDLR, APOB, and PCSK9) has become more accessible, but it is not essential for diagnosis of FH, and is currently not widely used. However, identification of a pathogenic variant is considered the ‘gold standard’ for FH diagnosis. Expanded FH panels can identify pathogenic variants in other hypercholesterolaemia genes, such as APOE, LIPA, and ABCG5/8. FH cascade screening is recommended to identify affected family members, and the benefits of early intervention to lower LDL-C and reduce the associated ASCVD burden are clear. National registries can also play a key role in identifying patients with FH. FH genetic testing should be incorporated as standard of care for patients and their relatives with suspected FH.

Roadmap to a career in preventive cardiology

While the concept of cardiovascular disease prevention spans a wide range of medical disciplines and specialties, few trainees receive dedicated, well-rounded training in this field which aims to curtail the...

Inflammation and Cardiovascular Disease: The Future.

Despite considerable advances in reducing the global burden of atherosclerotic cardiovascular disease by targeting conventional risk factors, significant residual risk remains, with low-grade inflammation being one of the strongest risk modifiers. Inflammatory processes within the arterial wall or systemic circulation, which are driven in a large part by modified lipoproteins but subsequently trigger a hypercoagulable state, are a hallmark of atherosclerotic cardiovascular disease and, in particular, its clinical complications. Extending conventional guideline-based clinical risk stratification algorithms by adding biomarkers of inflammation may refine phenotypic screening, improve risk stratification and guide treatment eligibility in cardiovascular disease prevention. The integration of interventions aimed at lowering the inflammatory burden, alone or in combination with aggressive lipid-modifying or even antithrombotic agents, for those at high cardiovascular risk may hold the potential to reduce the still substantial burden of cardiometabolic disease. This review provides perspectives on future clinical research in atherosclerosis addressing the tight interplay between inflammation, lipid metabolism and thrombosis, and its translation into clinical practice.

Autoimmune Rheumatic Diseases: An Update on the Role of Atherogenic Electronegative LDL and Potential Therapeutic Strategies.

Atherosclerosis has been linked with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Autoimmune rheumatic diseases (AIRDs) are associated with accelerated atherosclerosis and ASCVD. However, the mechanisms underlying the high ASCVD burden in patients with AIRDs cannot be explained only by conventional risk factors despite disease-specific factors and chronic inflammation. Nevertheless, the normal levels of plasma low-density lipoprotein (LDL) cholesterol observed in most patients with AIRDs do not exclude the possibility of increased LDL atherogenicity. By using anion-exchange chromatography, human LDL can be divided into five increasingly electronegative subfractions, L1 to L5, or into electropositive and electronegative counterparts, LDL (+) and LDL (−). Electronegative L5 and LDL (−) have similar chemical compositions and can induce adverse inflammatory reactions in vascular cells. Notably, the percentage of L5 or LDL (−) in total LDL is increased in normolipidemic patients with AIRDs. Electronegative L5 and LDL (−) are not recognized by the normal LDL receptor but instead signal through the lectin-like oxidized LDL receptor 1 (LOX-1) to activate inflammasomes involving interleukin 1β (IL-1β). Here, we describe the detailed mechanisms of AIRD-related ASCVD mediated by L5 or LDL (−) and discuss the potential targeting of LOX-1 or IL-1β signaling as new therapeutic modalities for these diseases.

Cost-effectiveness of statins for primary prevention of atherosclerotic cardiovascular disease among people living with HIV in the United States.

BackgroundExpanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States.MethodsWe developed a microsimulation model that randomly selected (with replacement) individuals from the Data‐collection on Adverse Effects of Anti‐HIV Drugs study with follow‐up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid‐lowering therapy. Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness‐to‐pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual’s probability of experiencing atherosclerotic cardiovascular disease over 20 years.ResultsPersons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost‐effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost‐effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal.ConclusionsPravastatin was projected to be cost‐effective compared with no statin. With substantial price reduction, pitavastatin may be cost‐effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV‐specific estimates on the efficacy of statins and the quality‐of‐life burden associated with taking an additional daily pill.

Dyslipidemia and Cardiovascular Disease Prevention in South Asians: A Review and Discussion of Causes, Challenges and Management Strategies.

South Asians are at a significantly increased risk of atherosclerotic cardiovascular disease (ASCVD). For a major portion of the South Asian population, the cardiovascular disease events occur at a relatively younger age, are associated with worse outcomes, and have potentially more severe socioeconomic implications compared to their western counterparts. The term "South Asian" typically constitutes individuals from India, Pakistan, Nepal, Bhutan, Bangladesh, Sri Lanka, and Maldives, including expatriates as well as their families from these countries. Based on this, South Asians form approximately 25% of the world's population, with a high ASCVD burden in this group. In this review, we discuss the pathophysiological factors underlying ASCVD in South Asians, the dyslipidemia types and management, and discuss approaches to improve the overall ASCVD prevention efforts in this large subset population of the world. Although the pathophysiological mechanisms underlying the excess risk of cardiovascular disease in South Asians are multifactorial, dyslipidemia is a primary risk factor for the incidence and prevalence of this disease. The traditional "South Asian" dyslipidemia pattern includes levels of low-density lipoprotein cholesterol (LDL-C) in the normal range with a high concentration of LDL particles, elevated triglycerides, low levels of high-density lipoprotein cholesterol (HDL-C) with dysfunctional HDL particles, and high levels of lipoprotein(a). While combined efforts to study the expatriate South Asians in western countries have been able to identify South Asian specific dyslipidemias, causal associations and optimal management remain relatively less explored. Larger scale studies are needed to better quantify the relationship of each lipid parameter with ASCVD risk among South Asians as well as optimal lipid targets and management strategies to reduce morbidity and mortality in this high-risk group.

Noise exposure at the place of residence is associated with atherothrombotic risk. Findings from ENVI-MI (Environment and Myocardial Infarction) study

Environmental factors including noise exposure are primary cardiovascular (CV) risk factors. ENVI MI project aimed to assess the impact of environmental noise at the home address in patients with acute myocardial infarction (MI). From the Côte d’Or infarction observatory (RICO) database, 867 consecutive MI patients living in an urban unit of Dijon (France), included from 2004 to 2008, without prior MI and discharged alive were analysed. Atherothrombotic risk stratification was performed using the TRS-2P score. Patients were divided in to 3 risk categories: G1 (low-risk, TRS-2P = 0/1); G2 (intermediate-risk, TRS-2P = 2); and G3 (high-risk, TRS-2P ≥ 3). Environmental noise prediction models were used to assess residential exposure. The relationship between TRS-2P categories were analyzed according to noise levels using ordinal logistic regression analysis; crude and adjusted odds ratios were estimated for an increase of 5 dB(A) in L DEN . Most patients were male (64%), with mean age at 68 ± 15 y, and LVEF was 55 ± 13%. Rate of CV risk factors were: smoking (57.2%), obesity (29.4%), hypertension (53.8%), hypercholesterolemia (46.4%), and diabetes (20.8%). TRS-2P categories were split in low (42%), intermediate (25%), and high (32%) risk. Most (51%) men were at low risk, while most women were at high risk (47%). Mean noise exposure was 60 ± 6 (min–max: 33-82) dB(A). Noise exposure was associated with atherothrombotic risk: OR(SD): 1.149(0.0142), P < 0.01). After adjustement, noise remains an independent estimate for atherothrombotic risk (OR(SD): 1.129(0.060), p < 0.05. Interestingly, the relationship was only significant for men (OR(SD): 1.220(0.075), p < 0.01), but not for women (OR(SD): 0.958(0.105), P = NS)). We found a significant association between noise exposure and atherosclerotic CV disease burden. If confirmed, these results could have major consequences in terms of public health, especially on post-MI management.

Should we treat high LDL cholesterol in ‘healthy’ elderly individuals?

Europe is an increasingly elderly society. In 2019, 14% of individuals in the European Union member countries were aged 65–79 years and about 6% were aged 80 years or more; over the next 20 years, the proportion aged at least 80 years is anticipated to more than double [1]. This is highly relevant in the context of prevention strategies aimed at reducing the burden of atherosclerotic cardiovascular disease (ASCVD).