Atherosclerotic Cardiovascular Disease Risk Management Research Articles

Cardiovascular Disease Epidemic in India and Triglyceride-Associated Residual Atherosclerotic Cardiovascular Disease Risk

Cardiovascular disease (CVD) is the leading global cause of mortality, with a significant rise in low- and middle-income countries. India faces a substantial burden of CVD, with alarming prevalence rates and an increase in associated deaths over the years. Despite a comparable cardiovascular death rate to Western populations, Indians developed atherosclerotic cardiovascular disease (ASCVD) a decade earlier. Lifestyle factors, genetic predisposition, and various risk factors contribute to this high prevalence. The management of ASCVD risk in India lifestyle measures, addressing risk factors such as sedentary lifestyle, unhealthy diet, obesity, metabolic syndrome, smoking, dyslipidemia, prediabetes, diabetes, and hypertension. Specifically, focusing on lipid management guidelines, low-density lipoprotein cholesterol (LDL-C) lowering is considered a crucial global need for additional interventions. This expert paper highlights the role of hypertriglyceridemia, its association with ASCVD, and the importance of managing triglyceride levels. Non-high-density lipoprotein cholesterol (nonHDL-C) and apolipoprotein B (Apo B) are highlighted as valuable indicators for assessing residual risk beyond LDL-C levels. The Lipid Association of India proposes non-HDL-C as a coprimary target, emphasizing the need for a comprehensive lipid management strategy, particularly in high-risk populations.

Atherosclerotic cardiovascular disease risk stratification and management in type 2 diabetes: review of recent evidence-based guidelines.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity in individuals with type 2 diabetes mellitus (T2DM). Accordingly, several scientific societies have released clinical practice guidelines to assist health professionals in ASCVD risk management in patients with T2DM. However, some recommendations differ from each other, contributing to uncertainty about the optimal clinical management of patients with T2DM and established ASCVD or at high risk for ASCVD. Thus, the purpose of this paper is to discuss recent evidence-based guidelines on ASCVD risk stratification and prevention in patients with T2DM, in terms of disparities and similarities. To close the gap between different guidelines, a multidisciplinary approach involving general practitioners, endocrinologists, and cardiologists may enhance the coordination of diagnosis, therapy, and long-term follow-up of ASCVD in patients with T2DM.

Concordance/discordance between serum apolipoprotein B, low density lipoprotein cholesterol and non-high density lipoprotein cholesterol in NATPOL 2011 participants – An epidemiological perspective

BackgroundThe study compared the distribution of serum LDL-C, non-HDL-C, and apolipoprotein B (apoB) among participants of the NATPOL 2011 survey and analysed concordance/discordance of results in the context of the risk for atherosclerotic cardiovascular disease (ASCVD). MethodsSerum levels of apoB, LDL-C, non-HDL-C and small dense LDL-C were measured/calculated in 2067–2098 survey participants. The results were compared between women and men, age groups and in relation to body mass index (BMI), fasting glucose and TG levels, and the presence of CVD. Percentile distribution of lipid levels and concordance/discordance analysis were based on medians and ESC/EAS 2019 target thresholds for ASCVD risk and on comparison of measured apoB levels and levels calculated from linear regression equations with serum LDL- C and non-HDL-C as independent variables. ResultsSerum apoB, LDL-C and non-HDL-C were similarly related to sex, age, BMI, visceral obesity, cardiovascular disease, and fasting glucose and triglyceride levels. Serum apoB, LDL-C and non-HDL-C very high- and moderate- target thresholds were exceeded in 83%, 99% and 96.9% and in 41%, 75% and 63.7% of subjects, respectively. The incidence of the discordances between the results depended on the dividing values used and ranged from 0.2% to 45.2% of the respondents. Subjects with high apoB / low LDL-C/non-HDL-C discordance had features of metabolic syndrome. ConclusionsDiagnostic discordances between apoB and LDL-C/non-HDL-C indicate limitations of serum LDL-C/non-HDL-C in ASCVD risk management. Due to the high apoB/low LDL-C/non-HDL-C discordance, obese/metabolic syndrome patients may benefit from replacing LDL-C/non-HDL-C by apoB in ASCVD risk assessment and lipid-lowering therapy.

High-Sensitivity C-Reactive Protein Modifies the Cardiovascular Risk of Lipoprotein(a): Multi-Ethnic Study of Atherosclerosis

BackgroundLittle is known about the relationship between lipoprotein (a) [Lp(a)] and high-sensitivity C-reactive protein (hsCRP) and their joint association with atherosclerotic cardiovascular disease (ASCVD). ObjectivesThe purpose of this study was to assess whether Lp(a)-associated ASCVD risk is modified by hsCRP in the context of primary prevention. MethodsThe current study included 4,679 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) Apolipoprotein ancillary data set. Cox proportional hazards models and Kaplan-Meier curves were used to assess the association among Lp(a), hsCRP, and time to cardiovascular disease (CVD) events. ResultsDuring a mean follow-up of 13.6 years, 684 CVD events occurred. A significant interaction was observed between Lp(a) and hsCRP (P = 0.04). With hsCRP <2 mg/L, no significant CVD risk was observed at any level of Lp(a) from <50 mg/dL to >100 mg/dL. However, with hsCRP ≥2 mg/L, a significant CVD risk was observed with Lp(a) of 50-99.9 mg/dL (HR: 1.36; 95% CI: 1.02-1.81) and Lp(a) ≥100 mg/dL (HR: 2.09; 95% CI: 1.40-3.13). Isolated elevations of either Lp(a) or hsCRP were not associated with increased CVD risk. In contrast, the combination of elevated Lp(a) (≥50 mg/dL) and hsCRP (≥2 mg/L) was independently associated with significant CVD risk (HR: 1.62; 95% CI: 1.25-2.10) and all-cause mortality (HR: 1.39; 95% CI: 1.12-1.72). ConclusionsLp(a)-associated ASCVD risk is observed only with concomitant elevation of hsCRP. Individuals with concomitant presence of elevated Lp(a) and systemic inflammation have greater ASCVD risk and all-cause mortality, and thus may merit closer surveillance and more aggressive ASCVD risk management.

941. Incarcerated patients living with HIV: Atherosclerotic cardiovascular disease risk and management

BackgroundThe 2018 American Heart Association and American College of Cardiology (AHA/ACC) 2018 Guideline on the Management of Blood Cholesterol included human immunodeficiency virus (HIV) as an atherosclerotic cardiovascular disease (ASCVD) risk enhancer for the first time. Our study investigates if patients living with HIV in the Illinois Department of Corrections (IDOC) were prescribed appropriate HMG-CoA reductase inhibitor (statin) therapy following release of these guidelines based on risk.MethodsThis was a retrospective study of patients with > 1 visit in our multidisciplinary HIV IDOC Telemedicine Clinic from 1/1/19-6/1/19. Our prescriptive authority is limited to HIV and directly related conditions, and we provide recommendations to on-site providers for other comorbidities. Included patients were > 18 years of age, HIV positive, and incarcerated within IDOC. Excluded patients had existing ASCVD. Data from the first visit in the study period were extracted from the electronic medical record and analyzed utilizing descriptive statistics. Primary objectives were to quantify ASCVD risk and appropriate statin use in our population.ResultsOf the 158 patients included, average age was 42 years. The majority were male (89%), Black (73%), overweight/obese (117/148, 79%), on an integrase single-tablet regimen (78%), with CD4 >200 cells/µL (97%), and HIV RNA < 20 copies/mL (85%). Of the 18 females, 8 were transgender. Within the prior year, 65% had a lipid panel. For the 50 patients meeting criteria for 10-year ASCVD estimation, median (range) risk was 6.6% (0.8% - 31.9%). Only 12 patients were on statins. Of these, all were indicated per AHA/ACC guidelines with 10 prescribed appropriate intensity. An additional 45 patients had indications for statins but were untreated. In total, 47 patients (30%) were not receiving appropriate statin therapy.ConclusionResults of our study suggest ASCVD risk management is an area of improvement for inmates living with HIV, especially as we look towards caring for an aging HIV population. Future directions include comparing these data to data from a later time point to evaluate time for guideline uptake.DisclosuresThomas D. Chiampas, PharmD, BCPS, AAHIVP, Gilead (Employee)

Measuring LDL-cholesterol: what is the best way to do it?

Cholesterol on low-density lipoproteins (LDL-C) is one of the main drivers of atherosclerotic cardiovascular disease (ASCVD) and hence its measurement is critical in the management of patients at risk. Although LDL-C has routinely been either calculated by the Friedewald equation or measured with direct assays, these methods have limitations, particularly for patients with dyslipidaemias, low LDL-C, and hypertriglyceridemia. The focus of this review will be recent advances in the measurement of LDL for ASCVD risk management. We first describe the recent recommendations on how LDL-C is used in ASCVD risk assessment and management. We then review the current approaches to the measurement of LDL-C and recent developments on new more accurate equations for calculating LDL-C. Finally, we present new and emerging LDL assays that may be superior to LDL-C for risk assessment, such as LDL particle number and small dense LDL-C, and several LDL-based lipid tests in early development. LDL-C is valuable in ASCVD risk management but recent improvements in its measurement and the development of other LDL-related tests may further improve its value.

Effects of weight change on apolipoprotein B-containing emerging atherosclerotic cardiovascular disease (ASCVD) risk factors

Background and aimsNon-high-density (HDL)-cholesterol, low-density lipoprotein (LDL)-particle number, apolipoprotein B, lipoprotein(a) (Lp(a)), and small-dense (sdLDL) and large-buoyant (lbLDL) LDL-subfractions are emerging apo B-containing atherosclerotic cardiovascular disease (ASCVD) risk factors. Current guidelines emphasize lifestyle, including weight loss, for ASCVD risk management. Whether weight change affects these emerging risk factors beyond that predicted by traditional triglyceride and LDL-cholesterol measurements remains to be determined.MethodRegression analyses of fasting ∆apo B-containing lipoproteins vs. ∆BMI were examined in a large anonymized clinical laboratory database of 33,165 subjects who did not report use of lipid-lowering medications. Regression slopes (±SE) were estimated as: *∆mmol/L per ∆kg/m2, †∆g/L per ∆kg/m2, ‡∆% per ∆kg/m2, and §∆μmol/L per ∆kg/m2.ResultsWhen adjusted for age, ∆BMI was significantly related to ∆nonHDL-cholesterol (males: 0.0238 ± 0.0041, P = 7.9 × 10− 9; females: 0.0330 ± 0.0037, P < 10− 16)*, ∆LDL-particles (males: 0.0128 ± 0.0024, P = 2.1 × 10− 7; females: 0.0114 ± 0.0022, P = 3.2 × 10− 7)*, ∆apo B (males: 0.0053 ± 0.0010, P = 7.9 × 10− 8; females: 0.0073 ± 0.0009, P = 2.2 × 10− 16)†, ∆sdLDL (males: 0.0125 ± 0.0015, P = 2.2 × 10− 16; females: 0.0128 ± 0.0012, P < 10− 16)*, ∆percent LDL carried on small dense particles (%sdLDL, males: 0.296 ± 0.035, P < 10− 16; females: 0.221 ± 0.023, P < 10− 16)‡, ∆triglycerides (males: 0.0358 ± 0.0049, P = 2.0 × 10− 13; females: 0.0304 ± 0.0029, P < 10− 16)*, and ∆LDL-cholesterol (males: 0.0128 ± 0.0034, P = 0.0002; females: 0.0232 ± 0.0031, P = 1.2 × 10− 13)* in both males and females. Age-adjusted ∆BMI was significantly related to ∆lbLDL in females (0.0098 ± 0.0024, P = 3.9 × 10− 5)* but not males (0.0007 ± 0.0026, P = 0.78)*. Female showed significantly greater increases in ∆LDL-cholesterol (P = 0.02) and ∆lbLDL (P = 0.008) per ∆BMI than males. ∆BMI had a greater effect on ∆LDL-cholesterol measured directly than indirect estimate of ∆LDL-cholesterol from the Friedewald equation. When sexes were combined and adjusted for age, sex, ∆triglycerides and ∆LDL-cholesterol, ∆BMI retained residual associations with ∆nonHDL-cholesterol (0.0019 ± 0.0009, P = 0.03)*, ∆LDL-particles (0.0032 ± 0.0010, P = 0.001)*, ∆apo B (0.0010 ± 0.0003, P = 0.0008)†, ∆Lp(a) (− 0.0091 ± 0.0021, P = 1.2 × 10− 5)§, ∆sdLDL (0.0001 ± 0.0000, P = 1.6 × 10− 11)* and ∆%sdLDL (0.151 ± 0.018, P < 10− 16) ‡.ConclusionsEmerging apo B-containing risk factors show associations with weight change beyond those explained by the more traditional triglyceride and LDL-cholesterol measurements.

Total cholesterol/HDL-cholesterol ratio discordance with LDL-cholesterol and non-HDL-cholesterol and incidence of atherosclerotic cardiovascular disease in primary prevention: The ARIC study.

The total cholesterol (TC)/high-density lipoprotein (HDL) cholesterol ratio may carry additional information not available in more commonly used single cholesterol measures. Analysis of discordance between lipid parameters might help assess the impact of such additional information on the risk of atherosclerotic cardiovascular disease. We aimed to investigate the role of the TC/HDL-cholesterol ratio in determining atherosclerotic cardiovascular disease risk when discordant with low-density lipoprotein (LDL) cholesterol and non-HDL-cholesterol. We studied 14,403 Atherosclerosis Risk in Communities (ARIC) study participants who were free of atherosclerotic cardiovascular disease at baseline. TC/HDL-cholesterol discordance with LDL-cholesterol (estimated by the novel Martin/Hopkins method) and non-HDL-cholesterol was assessed at five visits and determined by being at or above the median for each lipid parameter. We constructed Cox proportional hazard models to estimate the risk for incident atherosclerotic cardiovascular disease events associated with each lipid concordance/discordance category using a time-varying approach. Mean age of participants was 54.1 years, 56% women and 25% black. There were 2634 atherosclerotic cardiovascular disease events over a median (interquartile range) follow-up of 24.2 (16.0-25.4) years. Among individuals with LDL-cholesterol and non-HDL-cholesterol less than the median, 26% and 21% had discordant TC/HDL-cholesterol at or above the median, respectively. These individuals had a 24% (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09, 1.41) and 29% (HR 1.29, 95% CI 1.13, 1.46) greater risk of incident atherosclerotic cardiovascular disease, respectively, compared to those with TC/HDL-cholesterol less than the median after multivariable adjustment. In individuals with diabetes with LDL-cholesterol or non-HDL-cholesterol less than the median, discordant TC/HDL-cholesterol at or above the median was more prevalent at 48% and 38%, respectively. Clinically significant discordance exists between TC/HDL-cholesterol, available from the standard lipid profile, and the routinely used non-HDL-cholesterol and LDL-cholesterol. Such discordance may help inform atherosclerotic cardiovascular disease risk management, particularly in individuals with diabetes in whom discordance is more common.

Abdominal aortic calcification on dual-energy X-ray absorptiometry: Methods of assessment and clinical significance

Abdominal aortic calcification (AAC) can be accurately recognized on lateral spine images intended for vertebral fracture assessment, that are obtained with dual-energy X-ray absorptiometry (DXA). Greater amounts of AAC are common in the older population for whom DXA is routinely done, and have been consistently associated with incident atherosclerotic cardiovascular disease (ASCVD) events. AAC has also been associated with incident fractures in some prospective studies, but not in others. However, further research is needed to quantify the extent to which measurement of AAC improves prediction of ASCVD events and its impact on physician and patient ASCVD risk management. Additionally, research to develop better, more precise, automated, quantitative methods of AAC assessment on lateral spine densitometric images will hopefully lead to better prediction of clinical outcomes. In conclusion, although the prime indication for densitometric lateral spine imaging remains vertebral fracture assessment, AAC that is found incidentally on lateral spine images should be reported, so that patients and their health care providers are aware of its presence.