Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a).

Objective: Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort. Methods: Eligible participants were aged 40-70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus <50 mg/dL) over a median 26-year follow-up. Results: Among 2,990 persons meeting inclusion criteria (∼73 million US adults), the mean age was 50 years, 86% were non-Hispanic White, 9% were non-Hispanic Black, 53% were female, and 7% reported regular aspirin use. The median Lp(a) was 14 mg/dL and the proportion with elevated Lp(a) was similar among those with versus without regular aspirin use (15.1% versus 21.9%, p = 0.16). Among individuals with elevated Lp(a), the incidence of ASCVD mortality per 1,000 person-years was lower for those with versus without regular aspirin use (1.2, 95% CI: 0.1-2.3 versus 3.9, 95% CI: 2.8-4.9). In multivariable modeling, regular aspirin use was associated with a 52% lower risk of ASCVD mortality among individuals with elevated Lp(a) (HR=0.48, 95% CI: 0.28-0.83), but not for those without elevated Lp(a) (HR=1.01, 95% CI: 0.81-1.25; p-interaction=0.001). Conclusion: Regular aspirin use was associated with significantly lower ASCVD mortality in adults without clinical ASCVD who had elevated Lp(a). These findings may have clinical and public health implications for aspirin utilization in primary prevention.

The ABCs of the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease.

BACKGROUND: The 2023 Multisociety Guideline for the Management of Chronic Coronary Disease (CCD) updates recommendations for CCD, formerly known as "stable ischemic heart disease." This condition encompasses a spectrum of coronary vascular pathologies from subclinical to clinical ischemic heart disease. HYPOTHESIS: The new "ABC" mnemonic offers clinicians a streamlined framework for applying Class One Recommendations (COR1) and integrating recent updates into CCD management. METHODS: A critical analysis of the 2023 CCD guidelines was conducted, with this review highlighting key elements. RESULTS: The review outlines crucial changes, including novel recommendations supported by current clinical evidence. The focus is on these developments, clarifying their importance for day-to-day clinical practice. CONCLUSIONS: The review encourages a synergistic approach between primary healthcare providers and cardiologists to develop comprehensive strategies for lifestyle modification and medication therapy in CCD care. Furthermore, it suggests that utilizing comprehensive risk assessment tools can refine medical decision-making, ultimately enhancing patient care and clinical outcomes.

Polygenic risk and incident coronary heart disease in a large multiethnic cohort.

Objective: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort. Methods: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed. Results: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14-1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49-1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9-3.8) for the entire cohort and 9.7 (7.5-12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy. Conclusion: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.

Association of cardiovascular health with subclinical coronary atherosclerosis progression among five racial and ethnic groups: The MASALA and MESA studies.

BACKGROUND AND AIMS: South Asian adults (SA) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with other racial/ethnic groups. Life's Simple 7 (LS7) is a guideline-recommended, cardiovascular health (CVH) construct to guide optimization of cardiovascular risk factors. We sought to assess if the LS7 metrics predict coronary artery calcium (CAC) incidence and progression in asymptomatic SA compared with four other racial/ethnic groups. METHODS: We assessed the distribution of CVH metrics (inadequate: score 0-8, average: 9-10, optimal: 11-14, and per 1-unit higher score) and its association with incidence and progression of CAC among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study compared with other race/ethnic groups from the Multiethnic Study of Atherosclerosis (MESA). RESULTS: We included 810 SA, 2622 Non-Hispanic White (NHW), and 4192 Other adults (collectively 1893 Black, 1496 Hispanic and 803 Chinese American participants, respectively). SA and White participants compared to Other race/ethnicity groups were more likely to have optimal CVH metrics (26% SA vs 28% White participants vs 21% Other, respectively, p < 0.001). Similar to NHW and the Other race/ethnic group, SA participants with optimal baseline CVH were less likely to develop incident CAC on follow-up evaluation compared to participants with inadequate CVH metrics, optimal CVH/CAC = 0: 24% SA, 28% NHW, and 15% Other (p < 0.01). In multivariable linear and logistic regression models, there was no difference in annualized CAC incidence or progression between each race/ethnic group (pinteraction = 0.85 and pinteraction = 0.17, respectively). Optimal blood pressure control was associated with lower CAC incidence among SA participants [OR (95% CI): 0.30 (0.14-0.63), p < 0.01] and Other race and ethnicity participants [0.32 (0.19-0.53), p < 0.01]. CONCLUSIONS: Optimal CVH metrics are associated with lower incident CAC and CAC progression among South Asians, similar to other racial groups/ethnicities. These findings underscore the importance of optimizing and maintaining CVH to mitigate the future risk of subclinical atherosclerosis in this higher risk population.

Galectin-3, Metabolic Risk, and Incident Heart Failure: The ARIC Study.

BACKGROUND: It is unclear how metabolic syndrome (MetS) and diabetes affect Gal-3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal-3, and their joint associations with incident HF. METHODS AND RESULTS: We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996-1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross-sectional associations of metabolic risk categories with high Gal-3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal-3 quartiles with HF. In cross-sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio [OR], 1.24 [95% CI, 1.10-1.41]) and MetS with diabetes (OR, 1.59 [95% CI, 1.32-1.92]) were associated with elevated Gal-3. Over a median follow-up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal-3 in the lowest quartile, the combination of MetS with diabetes and Gal-3 ≥75th percentile was associated with a 4-fold higher HF risk (hazard ratio, 4.35 [95% CI, 3.30-5.73]). Gal-3 provided HF prognostic information above and beyond MetS, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, and CRP (C-reactive protein) (ΔC statistic for models with versus without Gal-3: 0.003; P=0.004). CONCLUSIONS: MetS and diabetes are associated with elevated Gal-3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal-3.

Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium >1,000.

BACKGROUND: Although a coronary artery calcium (CAC) of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. OBJECTIVES: Among persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. METHODS: The authors studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years). RESULTS: The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8]). CONCLUSIONS: Among asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.

Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals With Prediabetes: A Multicohort Study.

OBJECTIVE: To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes. RESEARCH DESIGN AND METHODS: We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to <126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to <6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to <126 mg/dL and HbA1c ≥5.7% to <6.5%, if available, among participants not taking glucose-lowering medications). RESULTS: The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th-75th percentile) follow-up time of 14.6 (interquartile range 7.8-16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100. CONCLUSIONS: CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes.

Recent advances in cardiovascular risk assessment: The added value of non-invasive anatomic imaging.

In 2022, multiple original research studies were conducted highlighting the utility of coronary artery calcium (CAC) imaging in young individuals and provided further evidence for the role of CAC to improve atherosclerotic cardiovascular disease (ASCVD) risk assessment. Mean calcium density was shown to be a more reliable predictor than peak density in risk assessment. Additionally, in light of the ACC/AHA/Multispecialty Chest Pain Guideline's recent elevation of coronary computed tomography angiography (CCTA) to a Class I (level of evidence A) recommendation as an index diagnostic test for acute or stable chest pain, several studies support the utility of CCTA and guided future directions. This review summarizes recent studies that highlight the role of non-invasive imaging in enhancing ASCVD risk assessment across different populations.

Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Applying the ABCs of Cardiovascular Disease Prevention to the 2023 AHA/ACC Multisociety Chronic Coronary Disease Guidelines.

The 2023 American Heart Association/American College of Cardiology Multisociety Guideline for the Management of Patients with Chronic Coronary Disease provides updated recommendations for the management of chronic coronary disease. The term "chronic coronary disease" reflects the lifelong nature of the disease and diverse disease etiologies that come under the chronic coronary disease umbrella, beyond the presence of epicardial coronary stenosis, which require targeted lifestyle recommendations, serial optimization of medications, and involvement of multiple care team members. In this review, we highlight several areas where a collaborative approach between cardiologists, primary care clinicians, and internists is essential to optimize the care of patients with chronic coronary disease.

Identification and Management of Atherosclerotic Cardiovascular Disease Risk in South Asian Populations in the U.S.

South Asians (SAs, individuals with ancestry from Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka) are among the fastest growing ethnic subgroups in the United States. SAs typically experience a high prevalence of diabetes, abdominal obesity, and hypertension, among other cardiovascular disease risk factors, which are often under recognized and undermanaged. The excess coronary heart disease risk in this growing population must be critically assessed and managed with culturally appropriate preventive services. Accordingly, this scientific document prepared by a multidisciplinary group of clinicians and investigators in cardiology, internal medicine, pharmacy, and SA-centric researchers describes key characteristics of traditional and nontraditional cardiovascular disease risk factors, compares and contrasts available risk assessment tools, discusses the role of blood-based biomarkers and coronary artery calcium to enhance risk assessment and prevention strategies, and provides evidenced-based approaches and interventions that may reduce coronary heart disease disparities in this higher-risk population.

Thoracic Aortic Calcium Density and Area in Long-Term Atherosclerotic Cardiovascular Disease Risk Among Men Versus Women.

BACKGROUND: The development of thoracic aortic calcium (TAC) temporally precedes coronary artery calcium more often in women versus men. Whether TAC density and area confer sex-specific differences in atherosclerotic cardiovascular disease (ASCVD) risk is unknown. METHODS: We studied 5317 primary prevention patients who underwent coronary artery calcium scoring on noncontrast cardiac gated computed tomography with TAC >0. The Agatston TAC score (Agatston units), density (Hounsfield units), and area (mm2) were compared between men and women. Cox proportional hazards regression calculated adjusted hazard ratios for TAC density-area groups with ASCVD mortality, adjusting for traditional risk factors, coronary artery calcium, and TAC. Multinomial logistic regression calculated adjusted odds ratios for the association between traditional risk factors and TAC density-area groups. RESULTS: The mean age was 60.7 years, 38% were women, and 163 ASCVD deaths occurred over a median of 11.7-year follow-up. Women had higher median TAC scores (97 versus 84 Agatston units; P=0.004), density (223 versus 210 Hounsfield units; P<0.001), and area (37 versus 32 mm2; P=0.006) compared with men. There was a stepwise higher incidence of ASCVD deaths across increasing TAC density-area groups in men though women with low TAC density relative to TAC area (3.6 per 1000 person-years) had survival probability commensurate with the high-density-high-area group (4.8 per 1000 person-years). Compared with low TAC density-area, low TAC density/high TAC area conferred a 3.75-fold higher risk of ASCVD mortality in women (adjusted hazard ratio, 3.75 [95% CI, 1.13-12.44]) but not in men (adjusted hazard ratio, 1.16 [95% CI, 0.48-2.84]). Risk factors most strongly associated with low TAC density/high TAC area differed in women (diabetes: adjusted odds ratio, 2.61 [95% CI, 1.34-5.07]) versus men (hypertension: adjusted odds ratio, 1.45 [95% CI, 1.11-1.90]). CONCLUSIONS: TAC density-area phenotypes do not consistently associate with ASCVD mortality though low TAC density relative to area may be a marker of increased ASCVD risk in women.

Higher HDL cholesterol levels are associated with increased markers of interstitial myocardial fibrosis in the MultiEthnic Study of Atherosclerosis (MESA).

Emerging research indicates that high HDL-C levels might not be cardioprotective, potentially worsening cardiovascular disease (CVD) outcomes. Yet, there is no data on HDL-C's association with other CVD risk factors like myocardial fibrosis, a key aspect of cardiac remodeling predicting negative outcomes. We therefore aimed to study the association between HDL-C levels with interstitial myocardial fibrosis (IMF) and myocardial scar measured by CMR T1-mapping and late-gadolinium enhancement (LGE), respectively. There were 1863 participants (mean age of 69 years) who had both serum HDL-C measurements and underwent CMR. Analysis was done among those with available indices of interstitial fibrosis (extracellular volume fraction [ECV]; N = 1172 and native-T1; N = 1863) and replacement fibrosis by LGE (N = 1172). HDL-C was analyzed as both logarithmically-transformed and categorized into < 40 (low),40-59 (normal), and ≥ 60mg/dL (high). Multivariable linear and logistic regression models were constructed to assess the associations of HDL-C with CMR-obtained measures of IMF, ECV% and native-T1 time, and myocardial scar, respectively. In the fully adjusted model, each 1-SD increment of log HDL-C was associated with a 1% increment in ECV% (p = 0.01) and an 18-ms increment in native-T1 (p < 0.001). When stratified by HDL-C categories, those with high HDL-C (≥ 60mg/dL) had significantly higher ECV (ß = 0.5%, p = 0.01) and native-T1 (ß = 7 ms, p = 0.01) compared with those with normal HDL-C levels. Those with low HDL-C were not associated with IMF. Results remained unchanged after excluding individuals with a history of myocardial infarction. Neither increasing levels of HDL-C nor any HDL-C category was associated with the prevalence of myocardial scar. Increasing levels of HDL-C were associated with increased markers of IMF, with those with high levels of HDL-C being linked to subclinical fibrosis in a community-based setting.

Preventing Adverse Cardiovascular Outcomes in Pregnancy Complicated by Obesity.

Purpose of review: Obesity is a chronic disease that is becoming increasingly prevalent, and more individuals of reproductive age have obesity prior to becoming pregnant. Obesity in pregnancy is associated with short- and long-term adverse consequences for both the birthing person and their offspring which have been associated with increased long-term cardiovascular morbidity and mortality. The goal of this review is to discuss what is currently understood about the relationship between maternal obesity and adverse pregnancy outcomes (APOs), the association between APOs and future cardiovascular disease (CVD) risk, and what evidence-based interventions can be implemented to prevent adverse outcomes in this population. Recent findings: Maternal obesity has been associated with an increased risk of APOs such as gestational diabetes, hypertensive disorders of pregnancy, and preterm birth as well as an increased risk of future CVD, such as metabolic syndrome, chronic hypertension, coronary heart disease, and stroke. The impact of maternal obesity also extends beyond the pregnant individual to the offspring, increasing the risk of fetal, neonatal, and infant mortality, as well as of congenital malformations, prematurity, and long-term health problems such as insulin resistance and childhood obesity. Prevention guidelines are incorporating the increased risk of adverse outcomes from maternal obesity into formalized risk assessments to guide both prenatal and postpartum care. It is becoming evident that a multidisciplinary cardio-obstetrics team is an important part of providing comprehensive care for pregnant individuals with obesity and other cardiovascular risk factors, including preexisting CVD and a history of prior APOs. There remains a need for further studies to better understand the mechanisms underlying the relationship between maternal obesity and APOs, as well as the racial and ethnic disparities that have been noted in the prevalence of APOs and associated CVD risk and mortality. Summary: There is increasing awareness that obesity in pregnancy is associated with various short- and long-term adverse maternal and offspring outcomes. There are multiple screening and prevention strategies that may be implemented before, during, and after pregnancy to prevent these adverse outcomes.

The AHA/ACC/HFSA 2022 Heart Failure Guidelines: Changing the Focus to Heart Failure Prevention.

The prevalence of heart failure (HF) in the United States (U.S.) is estimated at over 6 million adults, with the incidence continuing to increase. A large proportion of the U.S. population is also at risk of HF due to the high prevalence of established HF risk factors, such as hypertension, diabetes, and obesity. Many individuals have multiple risk factors, placing them at even higher risk. In addition, these risk factors disproportionately impact various racial and ethnic groups. Recognizing the rising health and economic burden of HF in the U.S., the 2022 American Heart Association / American College of Cardiology / Heart Failure Society of America (AHA/ACC/HFSA) Heart Failure Guideline placed a strong emphasis on prevention of HF. The purpose of this review is to highlight the role of both primary and secondary prevention in HF, as outlined by the recent guideline, and address the role of the preventive cardiology community in reducing the prevalence of HF in at-risk individuals.

Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways.

BACKGROUND: The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy. OBJECTIVES: The aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis. METHODS: Aptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies. RESULTS: Principal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling. CONCLUSIONS: Serum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.

Coronary artery calcium and sudden cardiac death: current evidence and future directions.

PURPOSE OF REVIEW: To provide a summary of the current evidence and highlight future directions regarding coronary artery calcium (CAC) and risk of sudden cardiac death (SCD). RECENT FINDINGS: Although up to 80% of all SCD is attributed to coronary heart disease (CHD), the subclinical atherosclerosis markers that help to improve SCD risk prediction are largely unknown. Recent observational data have demonstrated that, after adjustment for traditional risk factors, there is a stepwise higher risk for SCD across increasing CAC burden such that asymptomatic patients without overt atherosclerotic cardiovascular disease (ASCVD) experience a three-fold to five-fold higher SCD risk beginning at CAC at least 100 when compared with CAC = 0. Although the mechanisms underlying increasing CAC and SCD risk have yet to be fully elucidated, risk for myocardial infarction and scar, and/or exercise-induced ischemia may be potential mediators. SUMMARY: High CAC burden is an important risk factor for SCD in asymptomatic middle-aged adults, suggesting that SCD risk stratification can begin in the early stages of CHD via measurement of calcific plaque on noncontrast computed tomography. Despite the clinical inertia for downstream functional cardiac testing after detecting high CAC, comprehensive ASCVD prevention strategies should be the primary focus for SCD risk reduction.