Total Atherosclerotic Cardiovascular Disease Research Articles

Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

Abstract 14359: Life’s Essential 8 and Cardiovascular Health of Veterans: The Million Veteran Program

Background and Hypothesis: The American Heart Association (AHA) recently proposed the Life’s Essential 8 (LE8) score as an enhanced measurement tool for cardiovascular health. No studies to date have estimated its association with the risk for atherosclerotic cardiovascular disease (ASCVD) incidence and prognosis. Methods: A prospective cohort study of 384,518 Veterans enrolled in the VA Million Veteran Program (MVP) (2011-2021). LE8 score was developed using AHA guidelines. Primary outcome was total ASCVD. Secondary outcome was hard ASCVD which included non-fatal myocardial infarction, non-fatal stroke, and fatal CVD. Results: Based on 1.16 million person-years of follow-up among Veterans with no ASCVD at baseline, 46,295 Veterans had ASCVD events during follow-up. LE8 score was associated with ASCVD and its subtypes in a linear dose-response manner (Figure 1A). The overall population-attributable fractions for all non-ideal LE8 scores was 59% (95%CI: 51%-66%) for ASCVD, where non-ideal blood pressure was most influential (Figure 1B). Based on 0.6 million person-years of follow-up among patients with ASCVD at baseline, the hazard ratio for incident or recurrent hard ASCVD was 0.52 (95%CI: 0.48-0.56) comparing veterans with ≥650 to those with LE8 score &lt;350, with a dose-response linear association pattern. Conclusions: Based on 1.76 million person years of follow-up among Veterans, a high LE8 score was associated with a significantly lower ASCVD risk and a lower likelihood of developing adverse cardiovascular events regardless of ASCVD status at baseline. Theoretically, an ideal LE8 could potentially prevent almost 59% of ASCVD in this study. Our results support the importance of AHA’s promotion of LE8.

Intake of marine and plant-derived n-3 fatty acids and development of atherosclerotic cardiovascular disease in the Danish Diet, Cancer and Health cohort.

The objective of this study was to investigate the association between intake of seafood and plant-derived n-3 polyunsaturated fatty acids (PUFA) and development of total atherosclerotic cardiovascular disease (ASCVD) and acute major ischemic events. A total of 53,909 men and women were enrolled between 1993 and 1997 into the Danish Diet, Cancer and Health cohort and followed through nationwide Danish registries for development of total ASCVD defined as a first registration of myocardial infarction, peripheral artery disease, or ischemic stroke due to large artery atherosclerosis or small-vessel occlusion. At recruitment, the intake of the major marine n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the plant-derived n-3 PUFA, alpha-linolenic acid (ALA), was assessed using a validated food frequency questionnaire. Statistical analyses were conducted using sex-stratified multivariable Cox proportional hazard regression models. During a median of 13.5years of follow-up, 3958 participants developed ASCVD including 3270 patients with an acute major ischemic event. In multivariable analyses including adjustment for established risk factors, we found no associations for intake of ALA, but indications of inverse associations between intake of EPA, DHA and EPA + DHA and the rate of total ASCVD and acute major ischemic events. A high intake of marine n-3 PUFA was associated with a lower risk of total ASCVD and acute major ischemic events, whereas no association could be demonstrated for the plant-derived ALA.

Abstract 10288: Lipoprotein(a) and Long-Term Risk of Atherosclerotic Cardiovascular Disease in a US Pooled Cohort

Background: Lipoprotein(a) [Lp(a)] is a common genetic factor associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large prospective primary prevention cohorts of the US population, including those with diabetes. Methods: We examined the relation of Lp(a) with ASCVD outcomes in a pooled cohort of five major US prospective studies: the Multiethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, Jackson, Framingham Offspring, and Atherosclerosis Risk in Communities. Lp(a) levels were examined continuously (per 50 mg/dL) and categorically as follows: &lt;15 mg/dL (reference), 15-29 mg/dL, 30-49 mg/dL, 50-69 mg/dL, and &gt; 70 mg/dL. Cox regression, adjusted for age, sex, race/ethnicity, LDL-C, and other risk factors, examined the relation of Lp(a) levels with total incident ASCVD events (non-fatal and fatal myocardial infarction, stroke, revascularization, and coronary heart disease death) in the pooled cohort overall and among those at low-intermediate (&lt;20%) and high ( &gt; 20%) 10-year risk and in those with diabetes. Results: We included 27,756 persons without prior ASCVD (mean age 51.3 + 12.4 years, 55.0% female, and 35.7% black participants) who had a mean follow-up of 21.1 + 9.9 years for ASCVD events. The table below shows the adjusted hazard ratios (HRs) and 95% confidence intervals for Lp(a) levels in relation to ASCVD events. In the overall sample, a 50 mg/dL increment in Lp(a) was associated with a 26% greater risk and compared to &lt;15 mg/dL those with Lp(a) levels of 15-29 mg/dL, 30-40 mg/dL, 50-69 mg/dL, and &gt; 70 mg/dL had 10%, 31%, 44%, and 30% greater risks of ASCVD events. Relationships were stronger in those with diabetes. Conclusions: Our results demonstrate in a large pooled cohort of US prospective studies relationships of increased ASCVD risk begin above Lp(a) levels of 15 mg/dL, especially in those with diabetes.

Relation of First and Total Recurrent Atherosclerotic Cardiovascular Disease Events to Increased Lipoprotein(a) Levels Among Statin Treated Adults With Cardiovascular Disease

The relation between elevated lipoprotein(a) and total atherosclerotic cardiovascular disease (ASCVD) residual risk in persons with known cardiovascular disease on statin therapy is not well-established. We examined first and total recurrent ASCVD event risk in statin-treated adults with prior ASCVD. We studied 3,359 adults (mean age 63.6 years, 85.1% male) with prior ASCVD on statin therapy from the AIM-HIGH clinical trial cohort. The first and total ASCVD event rates were calculated by lipoprotein(a) [Lp(a)] categories. Cox regression and Prentice, Williams and Peterson (PWP) models provided hazard ratios (HRs) for ASCVD events over a mean follow-up of 3.3 years, adjusted for age, gender, trial treatment, LDL-C, and other risk factors. A total of 747 events occurred during follow-up, among which 544 were first events. First and total ASCVD event rates were greater with higher Lp(a) levels. Compared with Lp(a)<15 mg/dL, HRs (95% CIs) for subsequent total ASCVD events among Lp(a) levels of 15-<30, 30-<50, 50-<70, and ≥70 mg/dL were 1.04 (0.82 to 1.32), 1.15 (0.88 to 1.49), 1.27 (1.00 to 1.63) and 1.51 (1.25 to 1.84). Moreover, a continuous relation for total events was observed (HR=1.08 [1.04 to 1.12] per 20 mg/dL greater Lp(a). Findings for first ASCVD events and in those with LDL-C ≥70 mg/dL versus <70 mg/dL and with and without diabetes were similar. The risk of first and total ASCVD events is increased with Lp(a) levels of ≥70 mg/dL and ≥50 mg/dL, respectively, among adults with known CVD on statin therapy.

Abstract 15642: Race Sex Disparities in Atherosclerotic Cardiovascular Disease in Hospitalized Patients With Diabetes, 2005-2015 Potential Warning Signs for Future U.S. Public Health

Introduction: Despite a recent gradually slowing and perhaps recent increase in the burden of atherosclerotic cardiovascular disease (ASCVD) related hospitalization in the United States population with diabetes, it is unclear whether the prior downward trend was uniform or there was an unbalanced division amongst sex and race. Methods: Adults aged ≥40 years old with comorbid diabetes as a secondary diagnosis were identified using the U.S. 2005-2015 National (Nationwide) Inpatient Sample (NIS) data. The prevalence of other modifiable cardiovascular risk factors (hypertension, dyslipidemia, smoking/substance abuse, obesity, and renal failure), procedures like major amputations in the secondary diagnosis field and their association with ASCVD (acute coronary syndrome (ACS), coronary artery disease (CAD), stroke, or peripheral arterial disease (PAD)) as the first-listed diagnosis were determined. Complex samples multivariate regression was used to determine the odds ratio (O.D.) with 95% confidence limits (C.L.s). Sex and race risk-adjusted ASCVD related in-hospital mortality rates were estimated. Results: The rate of total ASCVD hospitalizations adjusted to the U.S. census population increased by 5.7% for black men compared to 4% for black women cumulatively compared to a stable downtrend in white men and white women. There was a higher odd of an ASCVD hospitalizations if there was comorbid hypertension (Odds Ratio (OR 1.29; 95% Confidence Interval (CI) 95% 1.28 - 1.31), dyslipidemia (OR 2.03; 95% CI 2.01 - 2.05), renal failure (OR 1.84; 95% CI 1.82 - 1.86), and smoking/substance use disorder (OR 1.31; 95% CI 1.29 - 1.33). When compared to white men, black men (OR 1.43; 95% CI 1.3 - 1.57) and black women (OR 1.15; 95% CI 1.04 - 1.27) had a higher likelihood of undergoing a major limb amputation during an ASCVD hospitalization. Conclusions: Blacks with diabetes continue to have a higher hospitalizations burden with a concomitant disparity in procedures and outcomes.

Diabetes associated residual atherosclerotic cardiovascular risk in statin-treated patients with prior atherosclerotic cardiovascular disease.

In statin-treated persons with atherosclerotic cardiovascular disease (ASCVD) the further ASCVD risk that diabetes mellitus (DM) adds is not well-quantified. We examined this residual risk for initial and total recurrent ASCVD events. We studied 3271 patients with ASCVD on statin therapy in the AIM-HIGH clinical trial cohort. Cox regression and the Prentice, Williams, and Peterson model examined the excess risk of initial and total recurrent ASCVD events associated with DM over a 3- year mean follow-up. Predictors of first and total ASCVD events in those with and without DM were also examined. Of our cohort with ASCVD on statin therapy 40% also had DM. Those with vs. without DM were older, were less likely to be male or white. They had higher systolic blood pressure, lower HDL-C, LDL-C, lipoprotein (a), but higher triglycerides and BMI (all p < 0.01). Adjusted HRs were 1.21 (95% CI; 1.01-1.46, p = 0.038) and 1.23 (95% CI: 1.05-1.44, p = 0.012) for first and total recurrent ASCVD events, respectively. Homocysteine and lipoprotein(a) most strongly predicted events in those with and without DM, respectively. In statin-treated patients with ASCVD, DM was associated with significantly greater residual risk over ASCVD alone for both first and total recurrent ASCVD events.

Racial disparity in atherosclerotic cardiovascular disease in hospitalized patients with diabetes 2005–2015: Potential warning signs for future U.S. public health

IntroductionThe pattern of atherosclerotic cardiovascular disease (ASCVD) and diabetes driven hospitalizations in the United States (U.S.) is unclear. We attempted to identify the disparate outcome in race related ASCVD hospitalizations with comorbid diabetes. MethodsAdults aged ≥40 years old with ASCVD (acute coronary syndrome (ACS), coronary artery disease (CAD), stroke, or peripheral arterial disease (PAD)) as the first-listed diagnosis with comorbid diabetes as a secondary diagnosis were determined using the U.S. 2005–2015 National (Nationwide) Inpatient Sample (NIS) data. The incidence of other modifiable cardiovascular risk factors (hypertension, dyslipidemia, smoking/substance abuse, obesity, and renal failure), in hospital procedures and outcomes was estimated. Complex samples multivariate regression was used to determine the odds ratio (OR) with 95% confidence Interval (CI) of risk associations and to determine patient comorbidity adjusted ASCVD related in-hospital mortality rate. ResultsThe rate of total ASCVD hospitalizations with comorbid diabetes adjusted to the U.S. census population increased by 5.7% for black men compared to 4% for black women. There was a higher odd of an ASCVD hospitalization if there was comorbid hypertension (Odds Ratio (OR 1.29; 95% CI 95% 1.28–1.31), dyslipidemia (OR 2.03; 95% CI 2.01–2.05), renal failure (OR 1.84; 95% CI 1.82–1.86), and smoking/substance use disorder (OR 1.31; 95% CI 1.29–1.33). White Women had the highest risk-adjusted incidence of ASCVD related in-hospital mortality (4.2%) relative to black women (3.9%), compared to white men (3.6%) and black men (3.5%) respectively. ConclusionsDespite improving treatment options for ASCVD in the diabetic population, blacks with diabetes continue to have a higher hospitalization burden with a concomitant disparity in comorbid presentation and outcome. Further evaluation is the need to understand these associations.

Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus

An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12), prior CVD (HR 8.48; 95% CI, 3.14-22.91), high total cholesterol (HR 1.43; 95% CI, 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08-0.63), statin use (HR 3.31; 95% CI, 1.31-8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35-7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18-0.96) was associated with coronary and/or cerebral events. HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.

1417-P: Lipoprotein(a)-Associated Residual Atherosclerotic Cardiovascular Disease Risk in Patients with Cardiovascular Disease on Statin Therapy by Diabetes Status

Background: The relation between elevated lipoprotein(a) [Lp(a)] and future atherosclerotic cardiovascular disease (ASCVD) in those with vs. without diabetes mellitus (DM) but known cardiovascular disease (CVD) is not clear. We examined recurrent ASCVD event risk by DM status in persons with known CVD on statin therapy. Methods: We studied 1,354 patients with and 2,005 patients without DM, all with prior CVD on statin therapy in the AIM-HIGH cohort. First and total recurrent ASCVD event rates were calculated by Lp(a) levels and the PWP model provided hazard ratios (HRs) for events over a mean follow-up of 3.3 years, adjusted for age, sex, trial treatment, LDL-C, and other risk factors. Results: ASCVD event rates (per 1000 person years) increased with Lp(a) levels ranging from &amp;lt;15 mg/dl to ≥70 mg/dL in non-DM: 39.7 to 74.1 for first and 48.5 to 87.3 for total recurrent events and in DM: 51.1 to 79.5 for first and 69.8 to 100.3 for total recurrent events. The Table shows HRs by Lp(a) categories for first and total recurrent ASCVD events. A higher risk for first recurrent events is noted at lower Lp(a) levels in those with vs. without DM. Conclusions: Higher Lp(a) levels predict residual ASCVD risk. However, ASCVD event risk may occur at lower levels of Lp(a) in those with vs. without DM. Future investigations in larger cohorts are needed to confirm these findings. Disclosure Y. Zhao: None. J.C. Sung: Employee; Self; Novartis Pharmaceuticals Corporation. A. Browne: Employee; Self; Novartis Pharmaceuticals Corporation. N.D. Wong: Advisory Panel; Self; Esperion Therapeutics, Inc. Research Support; Self; Amarin Corporation, Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Sanofi.

The low-density lipoprotein cholesterol lowering is an ineffective surrogate marker of statin responsiveness to predict cardiovascular outcomes

Statins therapy decrease both low-density lipoprotein cholesterol (LDL-C) levels and the risk of atherosclerotic cardiovascular disease (ASCVD) with considerable individual variability. Whether the amount of LDL-C lowering is a surrogate maker of statin responsiveness to ASCVD prevention has not been fully investigated. Among 2352 eligible patients with statin prescriptions in a cardiovascular center between January 2005 and February 2014, one-third of patients (33%) on statin therapy failed to achieve effective reductions in LDL-C (LDL-C level reduction of less than 15%). By using, propensity-score matched population (480 pairs, n = 960), the 5-year cumulative incidences of total major adverse cardiac events (MACE) were evaluated. The 5-year total MACE did not differ between normal cholesterol responders and non-responders (15.4% vs 16.1%, respectively; P = .860). In the subgroup analysis, male sex, older age, percutaneous coronary intervention, and heart failure were positive predictors, and dyslipidemia at the beginning of statin therapy was the only negative predictor of MACE in the 5-year follow-up (all P value < .05). However, cholesterol responsiveness after statin therapy did not influence the incidence of MACE (P = .860). The amount of LDL-C lowering did not predict beneficial effect on clinical outcomes of ASCVD after statin therapy. This result supports that given statin therapy, total ASCVD risk reduction should be tailored, which may not dependent to adherence to degree of LDL-C lowering or LDL-C goal based treatment.

P5341Predictive factors of atherosclerotic cardiovascular diseases events in HIV-HVC co-infected patients: results from hepavih ANRS co13 cohort

Abstract Introduction Several studies highlighted an increased risk of cardiovascular disease (CVD) in HIV-HCV co-infected patients without clearly identifying specific virologic factors associated with atherosclerotic CVD (ASCVD) events. Purpose Hence, we analyzed data collection from the French nationwide ANRS CO13 HEPAVIH cohort to determine the incidence of ASCVD events in HIV-HCV co-infected patients and the predictive factors associated with its occurrence. Methods The French multicenter nationwide ANRS CO13 HEPAVIH clinic-based cohort collected prospective clinical and biological data from HIV-HCV co-infected patients followed-up in 28 different university hospitals between December 2005 to November 2016. Participants with at least one year of follow-up were included. Primary outcome was the occurrence of major ASCVD events (cardiovascular death, acute coronary syndrome, coronary revascularization and stroke). Secondary outcomes were total ASCVD events including major ASCVD events and minor ASCVD events (peripheral arterial disease [PAD]). Incidence rates were estimated using Aalen-Johansen method and factors associated with ASCVD identified with Cox proportional hazards models. Results A total of 1213 patients were included: median age 45.4 years [42.1–49.0], 70.3% men, current smoking 70.2%, overweight 19.5%, liver cirrhosis 18.9%, chronic alcohol consumption 7.8%, diabetes mellitus (5.9%), personal history of CVD 2.7%, and statins use 4.1%. After a median follow-up of 5.1 years [3.9–7.0], 44 participants experienced at least one ASCVD event (26 major ASCVD event, and 20 a minor event). Incidences for total, major and minor ASCVD events were of 6.98 [5.19; 9.38], 4.01 [2.78; 6.00], and 3.17 [2.05; 4.92] per 1000 person-years, respectively. Personal history of CVD (Hazard Ratio (HR)=13.94 [4.25–45.66]), high total cholesterol (HR=1.63 [1.24–2.15]), low HDL cholesterol (HR=0.08 [0.02–0.34]) and undetectable HIV viral load (HR=0.41 [0.18–0.96]) were identified as independent factors associated with major ASCVD events while cirrhosis status, liver fibrosis and HCV sustained viral response were not. Cumulative incidence of CV events Conclusion HIV-HCV co-infected patients experience a high incidence of ASCVD events both coronary and peripheral artery diseases. Traditional CV risk factors are the main determinants of ASCVD whereas undetectable HIV viral load seems to be protective. Management of cholesterol abnormalities and controlling viral load are essential to modify this high cardiovascular risk. Acknowledgement/Funding Agence Natoinale de Recherche sur le SIDA et les Hépatites virales

Smoking and atherosclerotic cardiovascular disease risk in young men: the Korean Life Course Health Study

ObjectiveTo examine the effect of smoking on risk of atherosclerotic cardiovascular disease (ASCVD) in Korean young men and to examine whether serum total cholesterol levels could modify the effect of...

1462-P: Diabetes-Associated Residual Risk in Statin-Treated Patients with Atherosclerotic Cardiovascular Disease

Background: Persons with atherosclerotic cardiovascular disease (ASCVD) on statins remain at higher risk of CV events. The added residual risk that diabetes mellitus (DM) confers has not been well-quantified. We examined initial and total ASCVD events in statin treated persons with ASCVD and the added risk of DM. Methods: We studied 3,271 subjects with ASCVD on statins from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes trial cohort. We examined rates for first and total ASCVD events. Cox regression examined the risk of first ASCVD events over 3 years with and without DM at baseline. Results: 40% of subjects had DM. Those with vs. without DM were slightly older, less likely male, white, currently smoking, had higher systolic but lower diastolic blood pressure, lower HDL-C, LDL-C, lipoprotein (a), but higher triglycerides and BMI (all p&amp;lt;0.01). First and total ASCVD event rates are shown (Figure). Total ASCVD events were about 50% greater than initial events, with the difference largest in men with DM. From fully adjusted analyses, DM conferred a 22% greater risk of first ASCVD events compared to no DM (HR=1.22, 95% CI=1.03-1.44, p=0.02). Conclusion: Despite statin therapy, DM carries significantly greater residual risk over having ASCVD alone. More aggressive approaches are needed to reduce the increased risk with ASCVD and DM. Disclosure N.D. Wong: Advisory Panel; Self; Novartis Pharmaceuticals Corporation. Consultant; Self; Akcea Therapeutics, AstraZeneca. Research Support; Self; Amarin Corporation, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Y. Zhao: None. P. Xiang: Employee; Self; Amgen Inc. J.G. Lopez: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. Funding Amgen Inc.

Assessment of statin therapy in non-diabetic patients attending a medical clinic in a tertiary care institution of Sri Lanka

Background: Dyslipidaemia is a major risk factor for Atherosclerotic Cardiovascular Disease (ASCVD) and cholesterol lowering treatment reduces cardiovascular risk. The 2013 American College of Cardiology (ACC) /American Heart Association (AHA) guidelines on dyslipidaemia, provide an important framework for the cardiovascular risk reduction strategy. Objectives: To assess treatment gaps regarding statin therapy among patients without diabetes presenting to a medical clinic using standards set by the 2013 ACC/AHA guidelines. Methodology: A descriptive cross-sectional study was conducted for 6 months from December 2016, at the outpatient medical clinic, Teaching Hospital Kandy. A sample of nondiabetic patients, between 40-75 years was included. Data such as patient demographics, ASCVDs, cardiac risk factors, blood pressure, lipid levels and statin history were gathered from patients and their clinic records. Statin requirement was assessed according to the guidelines. Results: A total of 496 subjects were included. Mean age was 57.4 (SD 8.4) years and 66.5% were females. 270 (54.4%) patients were recognized to benefit from statin therapy, and the rest not to benefit from statin therapy. From 270 statin benefit patients, only 72 (26.6%) were on the recommended dose of statin therapy and 70 (25.9%) were not being treated with any statin. 144/226 (63.7%) patients who were non statin benefit were taking a statin. Conclusions: A majority of patients who required statin therapy were not on a statin or on the recommended dose, whereas a large number of patients who did not require a statin were on a statin. It is recommended to initiate statin therapy in appropriate dose after assessing total ASCVD risk.

Ideal cardiovascular health and incidence of atherosclerotic cardiovascular disease among Chinese adults: the China-PAR project.

Existing evidence on the relationship between cardiovascular health (CVH) metrics and cardiovascular disease (CVD) was primarily derived from western populations. We aimed to evaluate the benefits of ideal CVH metrics on preventing incident atherosclerotic CVD (ASCVD) in Chinese population. This study was conducted among 93,987 adults from the China-PAR project (Prediction for ASCVD Risk in China) who were followed up until 2015. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVH metrics for the risk of ASCVD, including coronary heart disease (CHD), stroke and ASCVD death. We further estimated the population-attributable risk percentage (PAR%) of these metrics in relation to each outcome. We observed gradient inverse associations between the number of ideal CVH metrics and ASCVD incidence. Compared with participants having ≤2 ideal CVH metrics, the multivariable-adjusted HRs (95% CIs) of ASCVD for those with 3, 4, 5, 6 and 7 ideal CVH metrics were 0.83 (0.74-0.93), 0.66 (0.59-0.74), 0.55 (0.48-0.61), 0.44 (0.38-0.50) and 0.24 (0.18-0.31), respectively (P for trend <0.0001). Approximately 62.1% of total ASCVD, 38.7% of CHD, 66.4% of stroke, and 60.5% of ASCVD death were attributable to not achieving all the seven ideal CVH metrics. After adjusting effects of ideal health factors, having four ideal health behaviors could independently bring adults health benefits in preventing 17.4% of ASCVD, 18.0% of CHD, 16.7% of stroke, and 10.1% of ASCVD death. Among all the seven CVH metrics, to keep with ideal blood pressure (BP) implied the largest public health gains against various ASCVD events (PAR% between 33.0% and 47.2%), while ideal diet was the metric most difficult to be achieved in the long term. Our study indicates that the more ideal CVH metrics adults have, the less ASCVD burden there is in China. Special efforts of health education and behavior modification should be made on keeping ideal BP and dietary habits in general Chinese population to prevent the epidemic of ASCVD.

Long-Term Risk of Atherosclerotic Cardiovascular Disease in US Adults With the Familial Hypercholesterolemia Phenotype.

Heterozygous familial hypercholesterolemia (FH) affects up to 1 in 200 individuals in the United States, but atherosclerotic cardiovascular disease (ASCVD) outcomes of FH in the general US population have not been described. We therefore sought to evaluate long-term coronary heart disease (CHD) and total ASCVD risks in US adults with an FH phenotype. Using individual pooled data from 6 large US epidemiological cohorts, we stratified participants by low-density lipoprotein cholesterol level at index ages from 20 to 79 years. For the primary analysis, low-density lipoprotein cholesterol levels ≥190 and <130 mg/dL defined the FH phenotype and referent, respectively. Sensitivity analyses evaluated the effects of varying the FH phenotype definition. We used Cox regression models to assess covariate-adjusted associations of the FH phenotype with 30-year hazards for CHD (CHD death or nonfatal myocardial infarction) and total ASCVD (CHD or stroke). We included 68 565 baseline person-examinations; 3850 (5.6%) had the FH phenotype by the primary definition. Follow-up across index ages ranged from 78 985 to 308 378 person-years. After covariate adjustment, the FH phenotype was associated with substantially elevated 30-year CHD risk, with hazard ratios up to 5.0 (95% confidence interval, 1.1-21.7). Across index ages, CHD risk was accelerated in those with the FH phenotype by 10 to 20 years in men and 20 to 30 years in women. Similar patterns of results were found for total ASCVD risk, with hazard ratios up to 4.1 (95% confidence interval, 1.2-13.4). Alternative FH phenotype definitions incorporating family history, more stringent age-based low-density lipoprotein cholesterol thresholds, or alternative lipid fractions decreased the FH phenotype prevalence to as low as 0.2% to 0.4% without materially affecting CHD risk estimates (hazard ratios up to 8.0; 95% confidence interval, 1.0-61.6). In the general US population, the long-term ASCVD burden related to phenotypic FH, defined by low-density lipoprotein cholesterol ≥190 mg/dL, is likely substantial. Our finding of CHD risk acceleration may aid efforts in risk communication.

Smoking and atherosclerotic cardiovascular disease in women with lower levels of serum cholesterol

This cohort study of Koreans examines the relationship between smoking on atherosclerotic cardiovascular disease (ASCVD) and whether serum levels of total cholesterol modify the impact of smoking on ASCVD. A 10-year prospective cohort study was carried out on 234,399 Korean women, ranging 40–69 years of age who received health insurance from the National Health Insurance Corporation and had a medical evaluation in 1993. The main outcome measures were hospital admissions and deaths from ischemic heart disease (IHD), cerebrovascular disease (CVD), and total ASCVD. At baseline, 13,696 (5.8%) were current smokers and 105,755 (45.1%) had a total cholesterol <200 mg/dl. Between 1994 and 2003, 4534 IHD (176/100,000 person year), 7961 CVD (310/100,000 person year), and 2418 other ASCVD events (94/100,000 person year) occurred. In multivariate Cox proportional hazard models controlling for age, hypertension, hypercholesterolemia, diabetes and alcohol drinking, current smoking increased the risk of IHD [hazard ratio (HR) = 1.7 (95% CI: 1.5–1.9)], CVD [HR = 1.6 (95% CI: 1.5–1.6)], and total ASCVD events [HR = 1.6 (95% CI: 1.5–1.7)]. Throughout the range of serum cholesterol levels, current smoking significantly increased the risk of myocardial infarction and CVD, but not angina pectoris. There was no evidence of an interaction between smoking and serum cholesterol ( p for interaction = 0.469, 0.612, and 0.905 for IHD, CVD, and total ASCVD, respectively). This study demonstrated that smoking was a major independent risk factor for IHD, CVD and ASCVD in Korean women. A low cholesterol level confers no protective benefit against smoking-related ASCVD.

What impact will current trial data have on future guideline recommendations?

The current Third Joint European Societies' Guidelines on Cardiovascular Disease Prevention in Clinical Practice reflect an active approach to cardiovascular disease (CVD) prevention. These guidelines have shifted the emphasis from coronary heart disease to total atherosclerotic CVD. A new risk prediction system, Systematic Coronary Risk Evaluation (SCORE), has been developed to define risk in terms of absolute 10-year risk of a fatal cardiovascular event. The definition of high risk has also been refined. The currently recommended goals for total and low-density lipoprotein (LDL) cholesterol are based on the evidence pool that was available at the time of publication. More recent evidence from the Heart Protection Study (HPS), the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA), and the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial indicates that lowering LDL cholesterol levels beyond the currently recommended goals can produce incremental reductions in cardiovascular morbidity and mortality. Results from the recently completed Treating to New Targets (TNT) study lend further support to implementing lower lipid goals than those currently suggested by guidelines. Results from the ongoing Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL) trial may provide additional evidence in support of the implementation of lower lipid goals. Nevertheless, the scope of future guidelines extends well beyond lipid targets. Guidelines of the future are likely to provide increasingly comprehensive recommendations on combined risk reduction, to publicize the characteristics of healthy people by highlighting acceptable levels of all cardiovascular risk factors, and to refine the concept of evidence-based medicine by shifting the focus from drug therapy to preventive therapy.

Association Between Estrogen Receptor ?? Gene Variation and Cardiovascular Disease

Estrogen and related hormones activate estrogen receptors, which in turn regulate genes for some cardiovascular disease (CVD) risk factors. Variants of the estrogen receptor a gene (ESR1) have been investigated, in small study populations, in relation to coronary artery disease and variation in levels of high-density lipoprotein (HDL) cholesterol, but little is known about the effects of genetic variation in ESR1 on CVD risk. This prospective study attempted to determine whether the ESR1 c.454-397T>C polymorphism correlates with CVD risk. Participants were 1739 unrelated men and women, ranging in age from 28 to 62 years, from the population-based offspring cohort of the Framingham Heart Study. Total atherosclerotic CVD events (recognized or unrecognized myocardial infarction [MI], angina pectoris, coronary insufficiency, intermittent claudication, death from coronary heart disease, atherothrombotic stroke) were present in 178 individuals followed up from 1971 to 1998. Major atherosclerotic CVD (recognized acute MI, coronary insufficiency, fatal coronary heart disease, atherothrombotic stroke) was found in 83 participants. Fifty-nine persons were recognized as having acute MI. One fifth of those participating in this study were homozygous for the ESR1c.454-397C allele. After adjusting for numerous covariates (age, gender, body mass index, hypertension, diabetes, total and high-density lipoprotein cholesterol, cigarette smoking), the CC genotype correlated significantly with major atherosclerotic CVD (odds ratio, 2.0; 95% confidence interval [CI], 1.3-3.2) compared with the CT or TT genotype. The risk of MI was 3-fold greater in those with the CC genotype (95% CI, 1.7-5.2). Comparable results were obtained when analyzing only men. Total atherosclerotic CVD did not appear to be associated with genotype. This study disclosed an association between a common estrogen receptor genotype, ESR1c.454-397CC, and an increased risk of MI. It seems likely that variations in estrogen receptors could help to explain the apparent effects of combination hormone therapy on the risk of CVD in women.