Objectives In this study, we systematically assessed the diagnostic and prognostic value of absence of coronary artery calcification (CAC) in asymptomatic and symptomatic individuals. Background ...Presence of CAC is a well-established marker of coronary plaque burden and is associated with a higher risk of adverse cardiovascular outcomes. Absence of CAC has been suggested to be associated with a very low risk of significant coronary artery disease, as well as minimal risk of future events. Methods We searched online databases (e.g., PubMed and MEDLINE) for original research articles published in English between January 1990 and March 2008 examining the diagnostic and prognostic utility of CAC. Results A systematic review of published articles revealed 49 studies that fulfilled our criteria for inclusion. These included 13 studies assessing the relationship of CAC with adverse cardiovascular outcomes in 64,873 asymptomatic patients. In this cohort, 146 of 25,903 patients without CAC (0.56%) had a cardiovascular event during a mean follow-up period of 51 months. In the 7 studies assessing the prognostic value of CAC in a symptomatic population, 1.80% of patients without CAC had a cardiovascular event. Overall, 18 studies demonstrated that the presence of any CAC had a pooled sensitivity and negative predictive value of 98% and 93%, respectively, for detection of significant coronary artery disease on invasive coronary angiography. In 4,870 individuals undergoing myocardial perfusion and CAC testing, in the absence of CAC, only 6% demonstrated any sign of ischemia. Finally, 3 studies demonstrated that absence of CAC had a negative predictive value of 99% for ruling out acute coronary syndrome. Conclusions On the basis of our review of more than 85,000 patients, we conclude that the absence of CAC is associated with a very low risk of future cardiovascular events, with modest incremental value of other diagnostic tests in this very low-risk group.
Background Clinical trials testing proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have demonstrated an unanticipated but significant lipoprotein (a) (Lp(a))-lowering effect, on the ...order of 25% to 30%. Although the 50% to 60% reduction in low-density lipoprotein (LDL)-cholesterol (LDL-C) achieved by PCSK9i is mediated through its effect on LDL receptor (LDLR) preservation, the mechanism for Lp(a) lowering is unknown. Objective We sought to characterize the degree of concordance between LDL-C and Lp(a) lowering because of PCSK9i in a standard of care patient cohort. Methods Participants were selected from our Center for Preventive Cardiology, an outpatient referral center in a tertiary academic medical center. Subjects were included in this study if they had (1) at least 1 measurement of LDL-C and Lp(a) before and after initiation of the PCSK9i; (2) baseline Lp(a) > 10 mg/dL; and (3) continued adherence to PCSK9i therapy. They were excluded if (1) they were undergoing LDL apheresis; (2) pre- or post-PCSK9i LDL-C or Lp(a) laboratory values were censored; or (3) subjects discontinued other lipid-modifying therapies. In total, 103 subjects were identified as taking a PCSK9i and 26 met all inclusion and exclusion criteria. Concordant response to therapy was defined as an LDL-C reduction >35% and an Lp(a) reduction >10%. Results The cohort consisted of 26 subjects (15 females, 11 males, mean age 63 ± 12 years). Baseline mean LDL-C and median Lp(a) levels were 167.4 ± 72 mg/dL and 81 mg/dL (interquartile range 38–136 mg/dL), respectively. The average percent reductions in LDL-C and Lp(a) were 52.8% (47.0–58.6) and 20.2% (12.2–28.1). The correlation between %LDL and %Lp(a) reduction was moderate, with a Spearman's correlation of 0.56 ( P < .01). All subjects except for 1 had a protocol-appropriate LDL-C response to therapy. However, only 16 of the 26 (62%; 95% confidence interval 41%–82%) subjects had a protocol-concordant Lp(a) response. Although some subjects demonstrated negligible Lp(a) reduction associated with PCSK9i, there were some whose Lp(a) decreased as much as 60%. Conclusions In this standard-of-care setting, we demonstrate moderate correlation but large discordance (∼40%) in these 2 lipid fractions in response to PCSK9i. The results suggest that pathways beyond the LDLR are responsible for Lp(a) lowering and indicate that PCSK9i have the potential to significantly lower Lp(a) in select patients, although confirmation in larger multicenter studies is required.
Cardiovascular outcomes for people with familial hypercholesterolaemia can be improved with diagnosis and medical management. However, 90% of individuals with familial hypercholesterolaemia remain ...undiagnosed in the USA. We aimed to accelerate early diagnosis and timely intervention for more than 1·3 million undiagnosed individuals with familial hypercholesterolaemia at high risk for early heart attacks and strokes by applying machine learning to large health-care encounter datasets.
We trained the FIND FH machine learning model using deidentified health-care encounter data, including procedure and diagnostic codes, prescriptions, and laboratory findings, from 939 clinically diagnosed individuals with familial hypercholesterolaemia (395 of whom had a molecular diagnosis) and 83 136 individuals presumed free of familial hypercholesterolaemia, sampled from four US institutions. The model was then applied to a national health-care encounter database (170 million individuals) and an integrated health-care delivery system dataset (174 000 individuals). Individuals used in model training and those evaluated by the model were required to have at least one cardiovascular disease risk factor (eg, hypertension, hypercholesterolaemia, or hyperlipidemia). A Health Insurance Portability and Accountability Act of 1996-compliant programme was developed to allow providers to receive identification of individuals likely to have familial hypercholesterolaemia in their practice.
Using a model with a measured precision (positive predictive value) of 0·85, recall (sensitivity) of 0·45, area under the precision–recall curve of 0·55, and area under the receiver operating characteristic curve of 0·89, we flagged 1 331 759 of 170 416 201 patients in the national database and 866 of 173 733 individuals in the health-care delivery system dataset as likely to have familial hypercholesterolaemia. Familial hypercholesterolaemia experts reviewed a sample of flagged individuals (45 from the national database and 103 from the health-care delivery system dataset) and applied clinical familial hypercholesterolaemia diagnostic criteria. Of those reviewed, 87% (95% Cl 73–100) in the national database and 77% (68–86) in the health-care delivery system dataset were categorised as having a high enough clinical suspicion of familial hypercholesterolaemia to warrant guideline-based clinical evaluation and treatment.
The FIND FH model successfully scans large, diverse, and disparate health-care encounter databases to identify individuals with familial hypercholesterolaemia.
The FH Foundation funded this study. Support was received from Amgen, Sanofi, and Regeneron.
Highlights • Often, a clinical diagnosis of familial hypercholesterolemia (FH) is established in the absence of a known mutation. • One important phenocopy of FH is lysosomal acid lipase deficiency. ...• There may be value in screening for lysosomal acid lipase deficiency in young patients with mutation-negative FH.
Reducing low-density lipoprotein (LDL) cholesterol with statins reduces cardiovascular risk, but the associations between increases in high-density lipoprotein (HDL) cholesterol and cardiovascular ...risk at different LDL levels have been less well characterized. To evaluate the associations between the 1-year changes in HDL cholesterol and LDL cholesterol with lovastatin and subsequent acute major coronary events (AMCEs), we studied 2,928 patients in the lovastatin arm who were followed for 5.2 years in a post-hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). The percentage of HDL cholesterol increase and apolipoproteins at year 1 and the incidence of AMCEs thereafter were assessed stratified by the LDL cholesterol levels. With lovastatin, LDL cholesterol was reduced by 25% on average to 115 mg/dl at year 1, and HDL cholesterol increased 6.0%. Patients with both an increase in HDL cholesterol of ≥7.5% and LDL cholesterol of <115 mg/dl at year 1 had the lowest event rate (3.53/1,000 person-years; p = 0.028). Similar results were found for an increase in HDL cholesterol of ≥7.5% and a decrease in LDL cholesterol of >25%, as well as for apolipoproteins A-I and B. The 1-year percent increase in HDL cholesterol appeared to be associated with a reduction in AMCEs in subsequent follow-up (p = 0.07 with the percentage of HDL cholesterol increase analyzed continuously). Patients with an HDL cholesterol increase of ≥7.5% had an AMCE rate of 5.18 compared with 7.66/1,000 person-years in patients with a lower HDL cholesterol increase (p = 0.08). In conclusion, lovastatin therapy was associated with a greater risk reduction of AMCEs when LDL cholesterol was substantially reduced and the HDL cholesterol increased by ≥7.5%.
Abstract Coronary artery calcium (CAC) scanning is an important tool for risk stratification in intermediate-risk, asymptomatic subjects without previous coronary disease. However, the clinical ...benefit of improved risk prediction needs to be balanced against the risk of the use of ionizing radiation. Although there is increasing emphasis on the need to obtain CAC scans at low-radiation exposure to the patient, very few practical documents exist to aid laboratories and health care professionals on how to obtain such low-radiation scans. The Tomographic Imaging Council of the Society for Atherosclerosis Imaging and Prevention, in collaboration with the Prevention Council and the Society of Cardiovascular Computed Tomography, created a task force and writing group to generate a practical document to address parameters that can be influenced by careful attention to image acquisition. Patient selection for CAC scanning should be based on national guidelines. It is recommended that laboratories performing CAC examinations monitor radiation exposure (dose-length-product DLP) and effective radiation dose (E) in all patients. DLP should be <200 mGy × cm; E should average 1.0–1.5 mSv and should be <3.0 mSv. On most scanner platforms, CAC imaging should be performed in an axial mode with prospective electrocardiographic triggering, using tube voltage of 120 kVp. Tube current should be carefully selected on the basis of patient size, potentially using chest lateral width measured on the topogram. Scan length should be limited for the coverage of the heart only. When patients and imaging parameters are selected appropriately, CAC scanning can be performed with low levels of radiation exposure.
Along with coronary evaluation, 64-slice multidetector computed tomography (MDCT) permits comprehensive assessment of left ventricular (LV) anatomy and function; however, how it compares with ...2-dimensional transthoracic echocardiography (TTE) in patients with heart failure (HF) is not known. In this study, we compared 25 patients with ejection fractions of <45% who underwent TTE and MDCT. The global ejection fraction by TTE versus MDCT was 36 ± 8% versus 38 ± 12% (r = 0.67, p = NS). The mean LV end-diastolic and end-systolic diameters by TTE and MDCT were 56 ± 8 and 46 ± 9 mm and 58 ± 12 and 47 ± 11 mm, respectively (r = 0.71 and 0.77, respectively, both p >0.20). The mean lateral and septal wall thicknesses by TTE and MDCT were 10 ± 1.4 and 11 ± 1.5 mm and 10 ± 1.3 and 10 ± 1.4 mm (r = 0.77 and 0.76, respectively, both p >0.20). The mean LV end-diastolic and end-systolic volumes and stroke volume by TTE and MDCT were 123 ± 45, 78 ± 31, and 44 ± 21 ml and 140 ± 58, 92 ± 43, and 48 ± 24 ml, respectively (r = 0.62, 0.67, and 0.60, respectively, all p >0.20). The regional wall motion assessment correlation was good between the 2 modalities (κ = 0.61). The interobserver correlation between the 2 MDCT readers ranged from good (r = 0.72 for LV end-diastolic volume) to excellent (r = 0.84 for septal wall thickness). In conclusion, MDCT provides comparable results to TTE for LV structure and functional assessment among patients with HF.
Abstract Morbidity and mortality from peripheral arterial disease (PAD) continues to increase. Traditional cardiovascular risk factors are implicated in the development of PAD, yet the extent to ...which those risk factors correlate with mortality in such patients remains insufficiently assessed. Using data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES), Cox proportional hazards models were used to examine the association of cardiovascular risk factors with all-cause and cardiovascular mortality. A total of 647 individuals ≥40 years old with PAD (i.e., ankle-brachial index ABI ≤ 0.9) were followed for a median 7.8 years. There were 336 deaths, of which 98 were attributable to cardiovascular disease. Compared to never smokers, current (hazard ratio HR 2.45; 95% confidence interval CI, 1.62–3.71) and former (HR 1.62; 95% CI, 1.14–2.29) smokers with PAD had higher rates of death. Moderate or vigorous physical activity ≥10 minutes monthly was associated with lower death rates (HR 0.63; 95% CI, 0.44-0.91). Also associated with increased rates of cardiovascular death were an ABI <0.5 (HR 2.56; 95% CI, 1.28–5.15, compared to those with ABI 0.7-0.9) and diabetes mellitus (HR 2.50; 95% CI, 1.33–4.73). Neither C-reactive protein nor body-mass index was associated with mortality. In conclusion, tobacco use increased risk of all-cause and cardiovascular death, while physical activity was associated with decreased mortality risk. A low ABI and diabetes were also predictive of cardiovascular death.
CVD Prevention – Primary and Secondary
Engaging in physical activity (PA) is an important modifiable risk factor to improve health in hypertension. However, the association between PA and outcomes in ...high-risk hypertension remains understudied. The aim of this study was to examine the relationship between the intensity and amount of PA and outcomes in SPRINT. SPRINT investigated the benefit of intensive blood pressure treatment on cardiovascular outcomes and all-cause mortality among individuals with high-risk hypertension.
This analysis included 8,320 (age 67.8±9.3, 34.9% women) participants from SPRINT on whom data was available on self-reported PA. Vigorous-intensity PA (VPA) included activities associated with sweating, increased heart rate or breathing. Moderate-Intensity PA (MPA) included activities such as brisk walking, climbing stairs or vacuuming. VPA was categorized into 2 groups based on frequency of “rarely or never” and ≥1 times/month. MPA was also categorized into 2 groups based on average duration/day of <15 minutes and ≥15minutes. Using multivariable Cox regression models, we examined the associations between VPA and MPA, and the primary outcome (defined as the composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes) and all-cause mortality.
Over a median follow-up of 3.8 years, 619 primary outcome and 419 all-cause mortality events occurred. Compared to participants who reported not engaging in VPA, those who engaged in VPA ≥ 1timess/month had an 18% and a 23% lower risk of the primary outcome and all-cause mortality; hazard ratio (HR) and 95% CIs of 0.82(0.69 -0.98; p=0.031) and 0.77(0.62-0.95, p=0.016) respectively. Similarly, those who did an average of ≥15 minutes/day of MPA compared to those who did <15 minutes/day, had a 21% and a 23% lower risk of the primary outcome and all-cause mortality; HR (95%CI) 0.79(0.65-0.96; p =0.0180) and 0.77(0.61-0.98; p=0.033) respectively (Figure).
Among individuals with high-risk hypertension but without diabetes mellitus, engaging in VPA at a threshold of ≥1 times/month and MPA at a threshold of ≥15 minutes/day, were both significantly associated with reduced risk of cardiovascular events and all-cause mortality. Further studies are required to identify the optimal volume and intensity of PA in high-risk hypertension.
To assess trends of stroke hospitalization rates, inpatient mortality, and health care resource use in young (aged ≤44 years), midlife (aged 45-64 years), and older (aged ≥65 years) adults.
We ...studied the National Inpatient Sample database (January 1, 2002 to December 31, 2017) to analyze stroke-related hospitalizations. We identified data using the International Classification of Diseases, Ninth/Tenth Revision codes.
Of 11,381,390 strokes, 79% (n=9,009,007) were ischemic and 21% (n=2,372,383) were hemorrhagic. Chronic diseases were more frequent in older adults; smoking, alcoholism, and migraine were more prevalent in midlife adults; and coagulopathy and intravenous drug abuse were more common in young patients with stroke. The hospitalization rates of stroke per 10,000 increased overall (31.6 to 33.3) in young and midlife adults while decreasing in older adults. Although mortality decreased overall and in all age groups, the decline was slower in young and midlife adults than older adults. The mean length of stay significantly decreased in midlife and older adults and increased in young adults. The inflation-adjusted mean cost of stay increased consistently, with an average annual growth rate of 2.44% in young, 1.72% in midlife, and 1.45% in older adults owing to the higher use of health care resources. These trends were consistent in both ischemic and hemorrhagic stroke.
Stroke-related hospitalization and health care expenditure are increasing in the United States, particularly among young and midlife adults. A higher cost of stay counterbalances the benefits of reducing stroke and mortality in older patients.
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