Analysis of lipid-lowering therapy in Chinese patients at high and very high risk of atherosclerotic cardiovascular disease

Background: Patients with early-stage breast cancer are more likely to die from cardiovascular disease (CVD) than breast cancer. Aromatase inhibitors (AI) are used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer to improve survival rates, however, AI use has numerous adverse effects including increasing the risk of CVD due to negative effects on blood pressure and cholesterol levels. The American College of Cardiology/American Heart Association 2019 guidelines recommend that all patients at intermediate or high risk for CVD based on 10-year atherosclerotic cardiovascular disease (ASCVD) risk score be on a statin. We aimed to evaluate CVD risk and statin use among racially/ethnically diverse women with breast cancer on adjuvant AI therapy. Methods: We evaluated postmenopausal women with stage I-III breast cancer treated with AIs between 2007 and 2018 at Columbia University Irving Medical Center in New York, NY. Ten-year ASCVD risk score was calculated at breast cancer diagnosis from age (20-79 years), gender (female only), race (white/black/other), serum total cholesterol (130-320 mg/dL) and HDL cholesterol (20-100 mg/dL), systolic blood pressure (90-200 mm Hg), hypertension treatment (yes/no), diabetes (yes/no), and smoking status (current/former/never). Individuals were categorized based upon their 10-year ASCVD risk as low (<5%), borderline (5-7.5%), intermediate (7.5-20%), or high risk (>20%). We used descriptive statistics and multivariable logistic regression to determine predictors of statin use among patients with intermediate or high risk ASCVD risk scores. Results: Of 363 evaluable patients, median age at diagnosis was 64 years (range, 50-80) and 35.8% were non-Hispanic white, 32.5% Hispanic, 23.4% non-Hispanic black, and 8.3% other races. Overall, the proportion of women with low risk ASCVD risk was 25.6%, borderline risk was 8.0%, intermediate risk was 37.7%, and high risk was 28.7%. Mean 10-year ASCVD risk scores were 13.7% for black women, 11.5% Hispanics, and 11.0% for white women and other races (p=0.082). The percentage of patients on statins was 50% in the intermediate risk category and 77% in the high risk category. Among those with intermediate or high ASCVD risk scores (N=240), statin use was associated with higher ASCVD risk, higher total cholesterol and systolic blood pressure, and a diagnosis of hypercholesterolemia. Conclusions: Among women with early-stage breast cancer starting adjuvant AI therapy, there is a high prevalence with intermediate and high ASCVD risk. Given the effects of AI therapy on CVD risk factors, these patients should be screened for ASCVD risk and started on statin therapy when indicated. Citation Format: Monica F Chen, Morgan Manger, Katherine D Crew. Cardiovascular disease risk and statin use among women with breast cancer treated with adjuvant aromatase inhibitor therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-07.

Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a foundation for the delivery of quality cardiovascular care. The ACC and AHA sponsor the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts. Clinical practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease (CVD). The focus is on medical practice in the United States, but these guidelines are relevant to patients throughout the world. Although guidelines may be used to inform regulatory or payer decisions, the intent is to improve quality of care and align with patients’ interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances, and should not replace clinical judgment. Recommendations for guideline-directed management and therapy, which encompasses clinical evaluation, diagnostic testing, and both pharmacological and procedural treatments, are effective only when followed by both practitioners and patients. Adherence to recommendations can be enhanced by shared decision-making between clinicians and patients, with patient engagement in selecting interventions on the basis of individual values, preferences, and associated conditions and comorbidities. The ACC/AHA Task Force on Clinical Practice Guidelines strives to ensure that the guideline writing committee both contains requisite expertise and is representative of the broader medical community by selecting experts from a broad array of backgrounds, representing different geographic regions, sexes, races, ethnicities, intellectual perspectives/biases, and scopes of clinical practice, and by inviting organizations and professional societies with related interests and expertise to participate as partners or collaborators. The ACC and AHA have rigorous policies and methods to ensure that documents are developed without bias or improper influence. The complete policy on relationships with industry and other entities (RWI) can be found online. Beginning in 2017, numerous modifications to the guidelines have been and continue to be implemented to make guidelines shorter and enhance “user friendliness.” Guidelines are written and presented in a modular knowledge chunk format, in which each chunk includes a table of recommendations, a brief synopsis, recommendation-specific supportive text and, when appropriate, flow diagrams or additional tables. Hyperlinked references are provided for each modular knowledge chunk to facilitate quick access and review. More structured guidelines–including word limits (“targets”) and a web guideline supplement for useful but noncritical tables and figures–are 2 such changes. This Preamble is an abbreviated version, with the detailed version available online. The reader is encouraged to consult the full-text guideline(P-1) for additional guidance and details, since the executive summary contains mainly the recommendations.

Klotho proteins (α- and β-Klotho) are transmembrane proteins whose extracellular domain is secreted into blood and urine by ectodomain shedding. As such they behave as circulating proteins that regulate cell metabolism, endothelial function and calcium homeostasis, as well as modulating the lifespan connected activity of Fibroblast Growth Factors (FGFs, mainly 21 and 23) and other molecules (1). Recent data have shown that highest levels of plasma circulating Klotho are associated with a lower cardiovascular risk, thereby suggesting a possible role for Klotho in cardiovascular diseases (2). However, although Klotho has been identified in various organs, including kidney, brain, adipose tissue and intestine, it is unknown whether cardiomyocytes express Klotho and FGFs and, if so, whether high cardiovascular risk can be associated with cardiac expression of Klotho, FGFs and other related molecules. We examined myocardial biopsies from 20 patients with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk in the range of 5% to 7.5% and 10 age-matched control subjects with an estimated 10-year ASCVD risk of <5% (3) undergoing cardiac surgery other than coronary artery by-pass. Both groups of patients were statin naive, had normal hemoglobin A1c, normal coronary arteries on left heart catheterization, and had LDL cholesterol levels between 70 and 189 mg/ DL. Using immunohistochemistry methods, we evaluated Klotho and FGFs expression in human cardiomyocytes, and whether higher ASCVD risk influenced the expression of other molecules involved in endoplasmic reticulum stress (GRP78), oxidative stress (SOD1, NFkB) and inflammation (iNOS, eNOS). Cardiomyocytes of patients with a higher ASCVD risk exhibited lower expression of Klotho, but also higher expression of FGFs, as compared to cardiomyocytes of patients with a reduced ASCVD risk. Furthermore, higher ASCVD risk was associated with significantly increased expression of GRP78, SOD1, NFkB and iNOS (all p<0.05). This study shows for the first time that Klotho proteins are inherently expressed in human cardiomyocytes and also that cardiac expression of Klotho is down regulated in higher ASCVD risk patients, while the expression of FGFs and other stress-related molecules involved in myocyte damage, such as GRP78, SOD1, NFkB and iNOS, is significantly increased. Further studies are warranted to investigate the association of klotho, FGFs and related molecules expression with cardiovascular risk.

DAHNA-An integrated innovative mobile application for the screening and personalised management of the atherosclerotic cardiovascular disease risk

Secondary Prevention for Atherosclerotic Cardiovascular Disease: Comparing Recent US and European Guidelines on Dyslipidemia.

Comparing Primary Prevention Recommendations: A Focused Look at United States and European Guidelines on Dyslipidemia.

High-intensity statins are recommended for all patients with familial hypercholesterolemia (FH) and non-statin lipid lowering therapies (LLTs) are indicated when there is an inadequate response to statins 1, 2 . In the pre-PCSK9 inhibitor (PCSK9i) era only about 40% of FH patients achieved an LDL-C level 3 . Partly based on the need for additional therapeutic options in high-risk FH patients, PCSK9 inhibitors were approved for treatment of heterozygous and homozygous FH in 2015. Nevertheless, emerging anecdotal data suggest that access to non-statin LLTs has been a challenge for FH patients though this has not been systematically evaluated. The FH Optimal Care of the US (FOCUS) study was designed by The FH Foundation to assess current treatment patterns of FH patients, and allowed us to assess rejection rates of PCSK9 inhibitors in those with FH or ASCVD.

BackgroundAcid–base imbalance has been reported to increase incidence of hypertension and diabetes. However, the association between diet-induced acid load and cardiovascular disease (CVD) risk in the general population has not been fully investigated.MethodsThis was a population-based, retrospectively registered cross-sectional study using nationally representative samples of 11,601 subjects from the Korea National Health and Nutrition Examination Survey 2008–2011. Individual CVD risk was evaluated using atherosclerotic cardiovascular disease (ASCVD) risk equations according to 2013 ACC/AHA guideline assessment in subjects aged 40–79 without prior CVD. Acid–base status was assessed with both the potential renal acid load (PRAL) and the dietary acid load (DAL) scores derived from nutrient intake.ResultsIndividuals in the highest PRAL tertile had a significant increase in 10 year ASCVD risks (9.6 vs. 8.5 %, P < 0.01) and tended to belong to the high-risk (10 year risk >10 %) group compared to those in the lowest PRAL tertile (odds ratio [OR] 1.23, 95 % confidence interval [CI] 1.22–1.35). The association between higher PRAL score and high CVD risk was stronger in the middle-aged group. Furthermore, a multiple logistic regression analysis also demonstrated this association (OR 1.20 95 % CI 1.01–1.43). Subgroup analysis stratified obesity or exercise status; individuals in unhealthy condition with lower PRAL scores had comparable ASCVD risk to people in the higher PRAL group that were in favorable physical condition. In addition, elevated PRAL scores were associated with high ASCVD risk independent of obesity, exercise, and insulin resistance, but not sarcopenia. Similar trends were observed with DAL scores.ConclusionDiet-induced acid load was associated with increased risk of CVD, independent of obesity and insulin resistance.

Cardiovascular Disease Risk and Statin Use Among Adults with Metabolic Dysfunction Associated Fatty Liver Disease

BackgroundThe influence of the historical cardiovascular risk status on future risk of atherosclerotic cardiovascular disease (ASCVD) is poorly understood. We aimed to investigate the association between 5-year changes in cardiovascular risk and ASCVD incidence.MethodsWe analyzed pooled data from seven community-based prospective cohort studies with up to 20 years of follow-up data. The study populations included White or Black participants aged 40–75 years without prevalent ASCVD. Cardiovascular risk was assessed using the pooled cohort equation and was categorized into non-high (< 20%) or high risk (≥ 20%). Changes in cardiovascular disease (CVD) risk over a 5-year interval were recorded. The main outcome was incident ASCVD.ResultsAmong 11,026 participants (mean [SD] age, 60.0 [8.1] years), 4272 (38.7%) were female and 3127 (28.4%) were Black. During a median follow-up period of 9.9 years, 2560 (23.2%) ASCVD events occurred. In comparison with individuals showing a consistently high CVD risk, participants whose CVD risk changed from non-high to high (hazard ratio [HR], 0.67; 95% confidence interval [CI] 0.59–0.77) or high to non-high (HR, 0.57; 95% CI 0.41–0.80) and those with a consistently non-high risk (HR, 0.33; 95% CI 0.29–0.37) had a lower risk of incident ASCVD. In comparison with individuals showing a consistently non-high CVD risk, participants whose CVD risk changed from high to non-high (HR, 1.74; 95% CI 1.26–2.41) or from non-high to high risk (HR, 2.04; 95% CI 1.84–2.27) and those with a consistently high risk (HR 3.03; 95% CI 2.69–3.42) also showed an increased risk of incident ASCVD.ConclusionsIndividuals with the same current CVD risk status but different historical CVD risks exhibited varying risks of future ASCVD incidents. Dynamic risk evaluation may enable more accurate cardiovascular risk stratification, and decision-making regarding preventive interventions should take the historical risk status into account.Graphical

Growing evidence has identified nocturia as a potential manifestation of several cardiovascular disease states. We aimed to determine whether a relationship exists between nocturia and global atherosclerotic cardiovascular disease (ASCVD) risk, defined by the American College of Cardiology/American Heart Association (ACC/AHA) ASCVD risk calculator, using a large nationally-representative study sample from the United States. We explored potential associations between nocturia and ASCVD risk in adults aged 40-79years with no prior history of overt/known atherosclerotic disease from 7 consecutive cycles of the National Health and Nutrition Examination Survey. Subjects were classified by whether they met the ASCVD high-risk threshold following current ACC/AHA consensus guidelines (10-year major adverse cardiovascular event risk ≥ 20%). Logistic regression analyses were used to explore associations between nocturia (defined as ≥ 2 nocturnal voids) and ASCVD risk. The prevalence of nocturia and high ASCVD risk were 27.0% and 10.9%, respectively. Nocturia, older age, increased body mass index, and diuretic use were associated with high ASCVD risk on univariate logistic regression. After adjusting for age, body mass index, and diuretic use, nocturia remained associated with significantly greater odds of high ASCVD risk in females but not in males. Elicitation of nocturia on clinical history taking may serve to identify high cardiovascular risk in females. Future studies are needed to elucidate mechanisms underlying this association.

An International Atherosclerosis Society Position Paper: Global recommendations for the management of dyslipidemia: Executive summary

BackgroundMexican Americans (MA) experience cognitive decline at younger ages and have higher rates of cardiovascular disease (CVD) than Non‐Hispanic whites (NHW). Persons who are depressed are more likely to have one or more risk factors for cardiovascular disease. The purpose of this study was to examine the impact of depression and Atherosclerotic Cardiovascular Disease (ASCVD) on cognitive function in MA and NHW.MethodData was collected from the Health and Aging Brain Study: Health Disparities (HABS‐HD) study. A total of 1094 participants who were classified as normal controls were stratified into 4 groups: no depression and low risk ASCVD (N= 684), no depression and high risk ASCVD (N= 222), depression and low risk ASCVD (N=140), and depression and high risk ASCVD (N=48). Depressive symptoms were assessed via Geriatric Depression Scale (GDS). ASCVD risk was calculated using a risk calculator. One‐way ANOVAs were conducted to examine differences in cognitive performance based on ASCVD risk and depression.ResultThe results showed that depressed NHW and MA males with a low ASCVD risk had significantly lower mean scores on Trail Making Test A than the non‐depressed with low ASCVD risk group (p &lt; 0.006), (p &lt; 0.017). Depressed MA males with high ASCVD risk had significantly lower mean scores on the MMSE than the non‐depressed low ASCVD risk group (p &lt; 0.00). Depressed NHW females with low ASCVD risk had significantly lower mean scores on delayed memory than the non‐depressed low ASCVD risk group (p &lt; 0.008). Depressed MA females with a high ASCVD risk demonstrated significantly lower mean scores on the COWA and SEVLT Trials 1‐5 and the non‐depressed low ASCVD risk group (p &lt; 0.002), (p &lt; 0.046).ConclusionThe results of this study indicated that depression and risk of ASCVD can impact cognitive functioning in different ways. In men depression impacted scores on Trails A. In MA women comorbid depression and high risk for ASCVD affect scores on the COWA and SEVLT. These findings support that medical comorbidities influence cognitive function. Future research directions include exploring the relationships between other CVD risk factors and depression.

Cardiovascular risk in elderly persons without established atherosclerotic cardiovascular disease

Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70–100 years: a contemporary primary prevention cohort