Total Atherosclerotic Cardiovascular Disease Events Research Articles

Effect of Population-Level Blood Pressure Treatment Strategies on Cardiovascular and Cognitive Outcomes.

The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia. Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population. Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages. Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia.

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.

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.

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.

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.

Fibroblast Growth Factor 21 is Related to Atherosclerosis Independent of Nonalcoholic Fatty Liver Disease and Predicts Atherosclerotic Cardiovascular Events.

BackgroundFGF21 (fibroblast growth factor 21), a novel hepatokine regulating lipid metabolism, has been linked to atherosclerotic disease. However, whether this relationship exists in patients without nonalcoholic fatty liver disease is unclear. We assessed the association between serum FGF21 levels and atherosclerosis in patients without nonalcoholic fatty liver disease, and investigated whether baseline FGF21 could predict incident atherosclerotic cardiovascular disease in a 7‐year prospective cohort.Methods and ResultsBaseline serum FGF21 was measured in a cross‐sectional cohort of 371 patients with type 2 diabetes mellitus without nonalcoholic fatty liver disease (determined by hepatic magnetic resonance spectroscopy), and in a population‐based prospective cohort of 705 patients from the Shanghai Diabetes Study. In the cross‐sectional study, FGF21 was significantly higher in patients with than in those without subclinical carotid atherosclerosis (P<0.01). The association remained significant after adjusting for demographic and traditional cardiovascular risk factors. In the prospective cohort, 80 patients developed atherosclerotic cardiovascular disease during follow‐up. Baseline FGF21 was significantly higher in those who developed ischemic heart disease or cerebral infarction than in those who did not. Using a cutoff serum concentration of 232.0 pg/mL, elevated baseline FGF21 independently predicted incident total atherosclerotic cardiovascular disease events, ischemic heart disease, and cerebral infarction in a nondiabetic population (all P<0.05), and significantly improved the discriminatory and reclassifying abilities of our prediction model after adjustment for established cardiovascular risk factors.ConclusionsThis study provides the first evidence that FGF21 levels are elevated in patients without nonalcoholic fatty liver disease with subclinical atherosclerosis. Baseline FGF21 is an independent predictor of atherosclerotic cardiovascular disease and represents a novel biomarker for primary prevention in the general population.

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

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.

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...

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.

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.

Association between estrogen receptor alpha gene variation and cardiovascular disease.

Estrogen and related hormone therapies activate estrogen receptors, which in turn regulate genes for several cardiovascular disease (CVD) risk factors. Relatively little is known, however, about the impact of genetic variation in estrogen receptor alpha (ESR1) on CVD risk. To investigate whether the ESR1 c.454-397T>C polymorphism is associated with CVD risk. Prospective study of 1739 unrelated men and women from the population-based offspring cohort of the Framingham Heart Study, who were followed up from 1971 to 1998. Total atherosclerotic CVD events, defined as recognized or unrecognized myocardial infarction (MI), angina pectoris, coronary insufficiency, intermittent claudication, coronary heart disease death, or atherothrombotic stroke (n = 178); major atherosclerotic CVD, defined as recognized acute MI, coronary insufficiency, coronary heart disease death, or atherothrombotic stroke (n = 83); and recognized acute MI (n = 59). Twenty percent of participants (n = 352) were homozygous for the ESR1 c.454-397C allele. After adjustment for covariates (age, sex, body mass index, hypertension, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and cigarette smoking), the CC genotype was significantly associated with major atherosclerotic CVD, with an odds ratio of 2.0 (95% confidence interval [CI], 1.3-3.2; P =.004) compared with individuals with the CT or TT genotypes. Participants with the CC genotype had 3.0-fold greater odds of MI (95% CI, 1.7-5.2; P<.001) compared with those with the CT or TT genotype. The results remained significant when analyses were restricted to men; too few women had events to study them separately. Individuals with the common ESR1 c.454-397CC genotype have a substantial increase in risk of MI. Whether ESR1 c.454-397T>C is causally related to MI risk or in linkage disequilibrium with 1 or more causal variants remains to be determined. These findings support the importance of estrogen receptors in CVD susceptibility, especially in men. Estrogen receptor variation also has potential to explain recent conflicting data regarding the effects of hormone therapy on CVD susceptibility in women.