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  1. Chang Y, Kim BK, Yun KE, Cho J, Zhang Y, Rampal S, et al.
    J Am Coll Cardiol, 2014 Jun 24;63(24):2679-86.
    PMID: 24794119 DOI: 10.1016/j.jacc.2014.03.042
    The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample of apparently healthy men and women.
  2. Parthiban N, Esterman A, Mahajan R, Twomey DJ, Pathak RK, Lau DH, et al.
    J Am Coll Cardiol, 2015 Jun 23;65(24):2591-2600.
    PMID: 25983009 DOI: 10.1016/j.jacc.2015.04.029
    BACKGROUND: Remote monitoring (RM) of implantable cardioverter-defibrillators (ICD) is an established technology integrated into clinical practice. One recent randomized controlled trial (RCT) and several large device database studies have demonstrated a powerful survival advantage for ICD patients undergoing RM compared with those receiving conventional in-office (IO) follow-up.

    OBJECTIVES: This study sought to conduct a systematic published data review and meta-analysis of RCTs comparing RM with IO follow-up.

    METHODS: Electronic databases and reference lists were searched for RCTs reporting clinical outcomes in ICD patients who did or did not undergo RM. Data were extracted from 9 RCTs, including 6,469 patients, 3,496 of whom were randomized to RM and 2,973 to IO follow-up.

    RESULTS: In the RCT setting, RM demonstrated clinical outcomes comparable with office follow-up in terms of all-cause mortality (odds ratio [OR]: 0.83; p = 0.285), cardiovascular mortality (OR: 0.66; p = 0.103), and hospitalization (OR: 0.83; p = 0.196). However, a reduction in all-cause mortality was noted in the 3 trials using home monitoring (OR: 0.65; p = 0.021) with daily verification of transmission. Although the odds of receiving any ICD shock were similar in RM and IO patients (OR: 1.05; p = 0.86), the odds of inappropriate shock were reduced in RM patients (OR: 0.55; p = 0.002).

    CONCLUSIONS: Meta-analysis of RCTs demonstrates that RM and IO follow-up showed comparable overall outcomes related to patient safety and survival, with a potential survival benefit in RCTs using daily transmission verification. RM benefits include more rapid clinical event detection and a reduction in inappropriate shocks.

  3. Dreyfus GD, Martin RP, Chan KM, Dulguerov F, Alexandrescu C
    J Am Coll Cardiol, 2015 Jun 2;65(21):2331-6.
    PMID: 26022823 DOI: 10.1016/j.jacc.2015.04.011
    The assessment of the etiology and severity of functional tricuspid regurgitation (FTR) has many limitations, especially when tricuspid regurgitation (TR) is more than severe. Instead of relying solely on TR severity, a new approach not only takes into account the severity of TR, but also pays strict attention to tricuspid annular dilation (size), the mode of tricuspid leaflet coaptation, and tricuspid leaflet tethering-factors often influenced by right ventricular enlargement and dysfunction. To simplify things, we propose a new staging system for functional tricuspid valve pathology using 3 parameters that may more accurately reflect the severity of the disease: TR severity, annular dilation, and mode of leaflet coaptation (extent of tethering). We believe that by utilizing these parameters, cardiologists and cardiac surgeons will be offered a better system for appraisal and decision-making in FTR.
  4. Alwi M, Geetha K, Bilkis AA, Lim MK, Hasri S, Haifa AL, et al.
    J Am Coll Cardiol, 2000 Feb;35(2):468-76.
    PMID: 10676696
    We compared the result of radiofrequency (RF)-assisted valvotomy and balloon dilation with closed surgical valvotomy and Blalock Taussig (BT) shunt as primary treatment in selected patients with pulmonary atresia and intact ventricular septum (PA-IVS).
  5. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al.
    J Am Coll Cardiol, 2017 Jul 04;70(1):1-25.
    PMID: 28527533 DOI: 10.1016/j.jacc.2017.04.052
    BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world.

    OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.

    METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.

    RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.

    CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.

  6. Bueno H, Rossello X, Pocock SJ, Van de Werf F, Chin CT, Danchin N, et al.
    J Am Coll Cardiol, 2019 09 17;74(11):1454-1461.
    PMID: 31514947 DOI: 10.1016/j.jacc.2019.06.068
    BACKGROUND: The relationship between in-hospital coronary revascularization rate (CRR) and post-discharge mortality rates in survivors of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) at a system level is unclear.

    OBJECTIVES: The purpose of this study was to evaluate CRR and 2-year post-discharge mortality rate (2YMR) in NSTE-ACS.

    METHODS: CRR and 2YMR were analyzed by hospital rate of CRR (in deciles), by country, and by world region in 11,931 patients with NSTE-ACS who survived to discharge and were enrolled in the EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients) and EPICOR Asia: twin multinational, observational, prospective cohort studies.

    RESULTS: Significant differences in patient baseline characteristics, medical therapies, CRR, and 2YMR were found. Mean CRR ranged from 0.0% to 96.8% in the first and tenth decile, respectively (p 

  7. Bilkis AA, Alwi M, Hasri S, Haifa AL, Geetha K, Rehman MA, et al.
    J Am Coll Cardiol, 2001 Jan;37(1):258-61.
    PMID: 11153748 DOI: 10.1016/s0735-1097(00)01094-9
    Objectives: The aim of the study was to assess the safety and efficacy of the Amplatzer ductal occluder (ADO) in transcatheter occlusion of patent ductus arteriosus (PDA).
    Background: Transcatheter closure of small to moderate sized PDAs is an established procedure. The ADO is a self-expandable device with a number of salutary features, notably its retrievability, ease of delivery via small 5F to 7F catheters and a range of sizes suitable even for the larger PDAs.
    Methods: Between November 1997 and August 1999, the ADO was successfully implanted in 205 of 209 patients with PDA. The inclusion criteria for this device occlusion method were patients with clinical and echocardiographic features of moderate to large PDA, weighing > or =3.5 kg as well as asymptomatic adolescents and adults with PDA measuring > or =5.0 mm on two-dimensional (2D) echocardiogram. Occlusion was achieved via the antegrade venous approach. Follow-up evaluations were performed with 2D echocardiogram, color-flow mapping and Doppler measurement of the descending aorta and left pulmonary artery velocity at 24 h and 1, 3, 6 and 12 months after implantation.
    Results: Two hundred and five patients had successful PDA occlusion using this device. The patients were between two months and 50 years (median 1.9) and weighed between 3.4 kg and 63.2 (median 8.4). Infants made up 26% of the total patients. The PDA measured from 1.8 to 12.5 mm (mean 4.9) at the narrowest diameter. Forty-four percent of patients achieved immediate complete occlusion. On color Doppler the closure rates at 24 h and 1 month after implant were 66% and 97%, respectively. At 6 and 12 months all except one patient attained complete occlusion. Device embolization occurred in three patients; in two this was spontaneous, and in the other it was due to catheter manipulation during postimplant hemodynamic measurement. Mild aortic narrowing was seen in an infant.
    Conclusions: Patent ductus arteriosus occlusion using ADO is safe and efficacious. It is particularly useful in symptomatic infants and small children with relatively large PDA. Embolization can be minimized by selection of appropriate sized devices, and caution should be exercised in infants <5 kg.
  8. Alwi M, Choo KK, Latiff HA, Kandavello G, Samion H, Mulyadi MD
    J Am Coll Cardiol, 2004 Jul 21;44(2):438-45.
    PMID: 15261945 DOI: 10.1016/j.jacc.2004.03.066
    Objectives: This study was designed to assess the safety, efficacy, medium-term outcome, and complications of patent ductus arteriosus (PDA) stenting in duct-dependent pulmonary circulation.
    Background: Patent ductus arteriosus stenting has been proposed as an alternative to surgical shunt on account of postoperative morbidity and complications of surgical shunting.
    Methods: Between April 2000 and February 2003, 69 patients with duct-dependent pulmonary circulation underwent cardiac catheterization with the intent of PDA stenting as first palliative procedure. Patients with critical pulmonary stenosis and pulmonary atresia with intact ventricular septum post-radiofrequency valvotomy who had PDA stenting were excluded. Thirteen more patients were excluded because of branch pulmonary artery (PA) stenosis. The follow-up was by clinical examination, echocardiography, and repeat cardiac catheterization at six to nine months following the procedure.
    Results: Patent ductus arteriosus stenting was successful in 51 patients (91.1%) and failed in 5 patients (8.9%). The mean narrowest PDA diameter was 1.9 +/- 0.6 mm. The mean procedure and fluoroscopy time were 95.7 min and 29.4 min, respectively. In one patient the stent dislodged and migrated to the left femoral artery and another patient developed transient intravascular hemolysis. There was no procedure-related mortality. Three patients (5.9%) died one day to two months after the procedure. At follow-up (3.2 months to 2.4 years), 8 patients developed significant stent stenosis requiring reintervention. Seven patients developed worsening of preexisting branch PA stenosis. The freedom from reintervention was 89% and 55% at 6 months and 1 year, respectively.
    Conclusions: Patent ductus arteriosus stenting is an attractive alternative to surgical shunt in a majority of patients with duct-dependent circulation. An absolute contraindication to this technique is the presence of branch pulmonary stenosis.
  9. Lewandowski AJ, Raman B, Bertagnolli M, Mohamed A, Williamson W, Pelado JL, et al.
    J Am Coll Cardiol, 2021 08 17;78(7):683-692.
    PMID: 34384550 DOI: 10.1016/j.jacc.2021.05.053
    BACKGROUND: Preterm birth affects about 10% of live births worldwide and is associated with cardiac alterations. Animal models of preterm birth suggest that left ventricular functional impairment may be due to an up-regulation of myocardial fibrosis.

    OBJECTIVES: The aim of this study was to determine whether diffuse left ventricular fibrosis is evident in young adults born preterm.

    METHODS: One hundred one normotensive young adults born preterm (n = 47, mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) were included from YACHT (Young Adult Cardiovascular Health sTudy). Left ventricular structure and function were quantified by cardiovascular magnetic resonance and echocardiography. Intravenous administration of a gadolinium-based contrast agent during cardiovascular magnetic resonance was used to quantify focal myocardial fibrosis on the basis of late gadolinium enhancement and, in combination with T1 mapping, to quantify diffuse myocardial fibrosis on the basis of assessment of myocardial extracellular volume fraction.

    RESULTS: Adults born preterm had smaller left ventricular end-diastolic and stroke volumes, with greater left ventricular mass and wall thickness (P < 0.001). In addition, longitudinal peak systolic strain and diastolic strain rate by both cardiovascular magnetic resonance and echocardiography, and E/A ratio measured by echocardiography, were lower in preterm-born compared to term-born adults (P < 0.05). Extracellular volume fraction was greater in preterm-born compared with term-born adults (27.81% ± 1.69% vs 25.48% ± 1.41%; P < 0.001) and was a significant mediator in the relationship between gestational age and both longitudinal peak diastolic strain rate and E/A ratio.

    CONCLUSIONS: Preterm-born young adults have greater extracellular volume fraction in the left ventricle that is inversely related with gestational age and may underlie their diastolic functional impairments.

  10. Stein EA, Dann EJ, Wiegman A, Skovby F, Gaudet D, Sokal E, et al.
    J Am Coll Cardiol, 2017 Aug 29;70(9):1162-1170.
    PMID: 28838366 DOI: 10.1016/j.jacc.2017.06.058
    BACKGROUND: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been formally evaluated in, or approved for, HoFH children.

    OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations.

    METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.

    RESULTS: Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.

    CONCLUSIONS: This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).

  11. Mahfoud F, Mancia G, Schmieder RE, Ruilope L, Narkiewicz K, Schlaich M, et al.
    J Am Coll Cardiol, 2022 Nov 15;80(20):1871-1880.
    PMID: 36357087 DOI: 10.1016/j.jacc.2022.08.802
    BACKGROUND: Renal denervation (RDN) has been shown to lower blood pressure (BP), but its effects on cardiovascular events have only been preliminarily evaluated. Time in therapeutic range (TTR) of BP is associated with cardiovascular events.

    OBJECTIVES: This study sought to assess the impact of catheter-based RDN on TTR and its association with cardiovascular outcomes in the GSR (Global SYMPLICITY Registry).

    METHODS: Patients with uncontrolled hypertension were enrolled and treated with radiofrequency RDN. Office and ambulatory systolic blood pressure (OSBP and ASBP) were measured at 3, 6, 12, 24, and 36 months postprocedure and used to derive TTR. TTR through 6 months was assessed as a predictor of cardiovascular events from 6 to 36 months using a Cox proportional hazard regression model.

    RESULTS: As of March 1, 2022, 3,077 patients were enrolled: 42.2% were female; mean age was 60.5 ± 12.2 years; baseline OSBP was 165.6 ± 24.8 mm Hg; and baseline ASBP was 154.3 ± 18.7 mm Hg. Patients were prescribed 4.9 ± 1.7 antihypertensive medications at baseline and 4.8 ± 1.9 at 36 months. At 36 months, mean changes were -16.7 ± 28.4 and -9.0 ± 20.2 mm Hg for OSBP and ASBP, respectively. TTR through 6 months was 30.6%. A 10% increase in TTR after RDN through 6 months was associated with significant risk reductions from 6 to 36 months of 15% for major adverse cardiovascular events (P < 0.001), 11% cardiovascular death (P = 0.010), 15% myocardial infarction (P = 0.023), and 23% stroke (P < 0.001).

    CONCLUSIONS: There were sustained BP reductions and higher TTR through 36 months after RDN. A 10% increase in TTR through 6 months was associated with significant risk reductions in major cardiovascular events from 6 to 36 months. (Global SYMPLICITY Registry [GSR] DEFINE; NCT01534299).

  12. Mensah GA, Fuster V, Murray CJL, Roth GA, Global Burden of Cardiovascular Diseases and Risks Collaborators
    J Am Coll Cardiol, 2023 Dec 19;82(25):2350-2473.
    PMID: 38092509 DOI: 10.1016/j.jacc.2023.11.007
  13. Cameron NA, Molsberry R, Pierce JB, Perak AM, Grobman WA, Allen NB, et al.
    J Am Coll Cardiol, 2020 Dec 01;76(22):2611-2619.
    PMID: 33183896 DOI: 10.1016/j.jacc.2020.09.601
    BACKGROUND: Rates of maternal mortality are increasing in the United States with significant rural-urban disparities. Pre-pregnancy hypertension is a well-established risk factor for adverse maternal and offspring outcomes.

    OBJECTIVES: The purpose of this study was to describe trends in maternal pre-pregnancy hypertension among women in rural and urban areas in 2007 to 2018 in order to inform community-engaged prevention and policy strategies.

    METHODS: We performed a nationwide, serial cross-sectional study using maternal data from all live births in women age 15 to 44 years between 2007 and 2018 (CDC Natality Database). Rates of pre-pregnancy hypertension were calculated per 1,000 live births overall and by urbanization status. Subgroup analysis in standard 5-year age categories was performed. We quantified average annual percentage change using Joinpoint Regression and rate ratios (95% confidence intervals [CIs]) to compare yearly rates between rural and urban areas.

    RESULTS: Among 47,949,381 live births to women between 2007 and 2018, rates of pre-pregnancy hypertension per 1,000 live births increased among both rural (13.7 to 23.7) and urban women (10.5 to 20.0). Two significant inflection points were identified in 2010 and 2016, with highest annual percentage changes between 2016 and 2018 in rural and urban areas. Although absolute rates were lower in younger compared with older women in both rural and urban areas, all age groups experienced similar increases. The rate ratios of pre-pregnancy hypertension in rural compared with urban women ranged from 1.18 (95% CI: 1.04 to 1.35) for ages 15 to 19 years to 1.51 (95% CI: 1.39 to 1.64) for ages 40 to 44 years in 2018.

    CONCLUSIONS: Maternal burden of pre-pregnancy hypertension has nearly doubled in the past decade and the rural-urban gap has persisted.

  14. Daelman B, Van Bulck L, Luyckx K, Kovacs AH, Van De Bruaene A, Ladouceur M, et al.
    J Am Coll Cardiol, 2024 Mar 26;83(12):1149-1159.
    PMID: 38508848 DOI: 10.1016/j.jacc.2024.01.021
    BACKGROUND: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential.

    OBJECTIVES: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits.

    METHODS: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment.

    RESULTS: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income.

    CONCLUSIONS: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.

  15. Maron MS, Mahmod M, Abd Samat AH, Choudhury L, Massera D, Phelan DMJ, et al.
    J Am Coll Cardiol, 2024 May 28;83(21):2037-2048.
    PMID: 38599256 DOI: 10.1016/j.jacc.2024.03.387
    BACKGROUND: In nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and exercise limitation. Ninerafaxstat, a novel cardiac mitotrope, enhances cardiac energetics.

    OBJECTIVES: This study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM.

    METHODS: Patients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient <30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption <80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The primary endpoint was safety and tolerability, with efficacy outcomes also assessed as secondary endpoints.

    RESULTS: A total of 67 patients with nHCM were enrolled at 12 centers (57 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) of patients in the placebo group. From baseline to 12 weeks, ninerafaxstat was associated with significantly better VE/Vco2 (ventilatory efficiency) slope compared with placebo with a least-squares (LS) mean difference between the groups of -2.1 (95% CI: -3.6 to -0.6; P = 0.006), with no significant difference in peak VO2 (P = 0.90). The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score was directionally, though not significantly, improved with ninerafaxstat vs placebo (LS mean 3.2; 95% CI: -2.9 to 9.2; P = 0.30); however, it was statistically significant when analyzed post hoc in the 35 patients with baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score ≤80 (LS mean 9.4; 95% CI: 0.3-18.5; P = 0.04).

    CONCLUSIONS: In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a phase 3 study.

  16. Wilkins JT, Ning H, Allen NB, Zheutlin A, Shah NS, Feinstein MJ, et al.
    J Am Coll Cardiol, 2024 Sep 10;84(11):961-973.
    PMID: 39232632 DOI: 10.1016/j.jacc.2024.05.070
    BACKGROUND: The ability of a 1-time measurement of non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear.

    OBJECTIVES: The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years.

    METHODS: We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non-HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non-HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years.

    RESULTS: Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non-HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non-HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non-HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non-HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non-HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile.

    CONCLUSIONS: Single measures of non-HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events.

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