Risk Assessment In Primary Prevention Research Articles

Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.

Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156). In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

Coronary artery calcification score and 19 biomarkers on cardiovascular events; a 10-year follow-up DanRisk substudy

Abstract Background SCORE2 is recommended for the estimation of the 10-year risk of cardiovascular disease (CVD), and guideance of medical therapy. However, the prediction is deficient. Coronary artery calcification (CAC) score has been proven to improve the risk assessment in primary prevention of CVD, however, it is also resource-intensive. Biomarkers may be an advantageous alternative. Purpose This study aims to determine and compare the additive value of CAC-score and 19 biomarkers in risk prediction. Methods Classic cardiovascular (CV) risk factors, CAC-score, and a wide range of blood samples (including lipids, calcium-phosphate metabolism, troponin, inflammation, and kidney function), were collected from 1,211 randomly selected middle-aged men and women in this multicentre prospective cohort in 2009-2010. 10-year follow-up data on CV-events (death from CVD, stroke, myocardial infarction, heart failure or coronary artery revascularization) were obtained from the Danish Health Registries. The association between SCORE2, CAC-score, biomarkers, and CV-events was displayed in Kaplan Meier diagrams, assessed using cox proportional hazard rates (HR) and compared using area under the curve (AUC) calculation of receiver operating characteristic (ROC) curves. The net reclassification improvement (NRI) for CAC-score compared to SCORE2 was also calculated. Results 92 participants had CV-events. Events were seen in 29.3% of 41 participants with a very high risk (SCORE2 ≥10%) and 24.2% of 66 participants with CAC-score ≥400. Adjusted for risk factors, CAC-score was significantly associated with events adjusted HR 1.91 (95%CI: 1.10;3.31), 3.61 (95%CI: 1.93;6.76), and 5.2 (95%CI: 2.63;10.29) for CAC-score 1-99, CAC-score 100-399 and CAC-score ≥400, respectively. HR for the highest quartile of C-reactive protein (CRP) was 2.34 (95%CI: 1.15;4.47), while none of the remaining biomarkers improved HR. CAC-score improved AUC of the SCORE2 model (AUC_CAC+SCORE2: 0.72, AUC_SCORE2: 0.67, p<0.01) as seen in Figure 1. A combination of selected biomarkers (total cholesterol, low-density lipoprotein, phosphate, troponin I, CRP, and creatinine) borderline improved AUC (AUC_Biomarkers+SCORE2: 0.71, AUC_SCORE2: 0.67, p=0.06). Inclusion of CAC-score in the SCORE2 model improved the risk prediction. For participants with a CV-event, 73.9% had increased probabilities and 26.1% had decreased probabilities, compared to 42.4% increased and 57.6% decreased probabilities for participants without an event. NRI was 63% (p<0.0001) Conclusion CAC-score remained to improve the prediction of CV-events, while the selected biomarkers did not.ROC of SCORE2 versus CAC-score+SCORE2

Role of Cardiovascular Imaging in Risk Assessment: Recent Advances, Gaps in Evidence, and Future Directions.

Optimal risk assessment for primary prevention remains highly challenging. Recent registries have highlighted major discrepancies between guidelines and daily practice. Although guidelines have improved over time and provide updated risk scores, they still fail to identify a significant proportion of at-risk individuals, who then miss out on effective prevention measures until their initial ischemic events. Cardiovascular imaging is progressively assuming an increasingly pivotal role, playing a crucial part in enhancing the meticulous categorization of individuals according to their risk profiles, thus enabling the customization of precise therapeutic strategies for patients with increased cardiovascular risks. For the most part, the current approach to patients with atherosclerotic cardiovascular disease (ASCVD) is homogeneous. However, data from registries (e.g., REACH, CORONOR) and randomized clinical trials (e.g., COMPASS, FOURIER, and ODYSSEY outcomes) highlight heterogeneity in the risks of recurrent ischemic events, which are especially higher in patients with poly-vascular disease and/or multivessel coronary disease. This indicates the need for a more individualized strategy and further research to improve definitions of individual residual risk, with a view of intensifying treatments in the subgroups with very high residual risk. In this narrative review, we discuss advances in cardiovascular imaging, its current place in the guidelines, the gaps in evidence, and perspectives for primary and secondary prevention to improve risk assessment and therapeutic strategies using cardiovascular imaging.

Role of Coronary Artery Calcium Testing for Risk Assessment in Primary Prevention of Atherosclerotic Cardiovascular Disease

Current guidelines recommend a few different approaches to the use of coronary artery calcium (CAC) testing as a tool for risk assessment and decision-making regarding drug therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium testing is not recommended for universal screening, particularly in patients at very low or high predicted risk for ASCVD, where its yield and utility for altering clinical decisions are limited. Use of CAC testing appears to be optimal when used in selected patients who are at intermediate or borderline risk of ASCVD as a sequential decision aid after initial quantitative risk assessment and consideration of individual patient risk-enhancing factors (eg, strong family history of premature ASCVD, chronic kidney disease). Although convincing clinical trials have not been completed, observational studies strongly suggest that, in those at intermediate risk, CAC testing can meaningfully reclassify risk and can support improved targeting of drug therapy to patients most likely to benefit. This narrative review summarizes the evidence available about the appropriate role of CAC testing for ASCVD risk assessment. Coronary artery calcium testing should be used selectively in patients who are at intermediate risk of ASCVD, when there is persistent uncertainty after performing standard risk assessment using traditional risk factors in a risk score, and after consideration of additional individual risk-enhancing factors. In these situations, the result of the CAC test can be helpful to clarify whether the patient's true risk is high enough to justify initiation of primary prevention medications, such as statins or aspirin.

Cardiovascular risk assessment for primary prevention in Malawian HIV patients on ART: are measurements of glycated hemoglobin and lipids worth the effort?

Cardiovascular risk assessment for primary prevention in Malawian HIV patients on ART: are measurements of glycated hemoglobin and lipids worth the effort?

Abstract P3009: Stenostiffness Approach for Cardiovascular Disease Risk Assessment in Primary Prevention

Background: The Japan Brachial-Ankle pulse wave VELocity individual participant data meta-analysis of prospective studies (J-BAVEL) studies are a series of individual participant data meta-analyses carried out to demonstrate the predictive ability, individually, of the inter-arm blood pressure difference (IAD), ankle-brachial pressure index (ABI), and brachial-ankle pulse wave velocity (brachia-ankle PWV) for the prediction of cardiovascular events in Japanese subjects. Purposes: Based on the findings of the J-BAVEL study series, we discuss here a strategy for integrating IAD, ABI, and brachial-ankle PWV (i.e., steno-stiffness approach) with the conventional cardiovascular disease (CVD) risk prediction model to improve the accuracy of CVD risk prediction in primary prevention. Methods and Results: The data of 1,1726 subjects without a past history of cardiovascular disease (CVD) in J-BAVEL study were re-analyzed. The IAD > 15 mm Hg (IAD15) was associated with a significant Cox stratified adjusted hazard ratio (HR) for subsequent stroke [2.42; 95% confidence interval (CI), 1.27-4.60; P <0.01]. The adjusted odds ratio of IAD10 for ABI ≤0.90 in the binary logistic regression analysis was 3.42 (95% CI 2.13-5.50; P < 0.001). Furthermore, among 10,512 subjects of J-BAVEL study cohort, subjects having either ABI ≤0.90 {n = 123 (1.2%)} or brachial-ankle PWV ≥15.9 m/sec {n = 3,837 (36.5%)} were defined as abnormal steno-stiffness markers. The addition of abnormal steno-stiffness marker to a model including the FRS improved the accuracy of prediction of the development of CVD (category-free net reclassification improvement: 0.391 [95% CI, 0.266-0.517], P < 0.001; integrated discrimination index: 0.0021 [95% CI, 0.0004-0.0038], P = 0.02). Conclusion: Steno-stiffness approach (i.e., IAD, ABI, and brachial-ankle PWV) to CVD risk assessment in primary prevention may be efficient. The IAD is a simply measured useful physiological marker of subclinical PAD (IAD10) or stroke (IAD15). Furthermore, the ABI ≤0.90 or brachial-ankle PWV > 15.9 m/sec may be efficient for the improvement of CVD risk assessment by conventional risk prediction model in primary prevention.

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

The Use of Risk Enhancing Factors to Personalize ASCVD Risk Assessment: Evidence and Recommendations from the 2018 AHA/ACC Multi-society Cholesterol Guidelines.

In 2018, the AHA/ACC multi-society Cholesterol Guidelines introduced the novel concept of risk-enhancing factors to be used as a supplement to the pooled cohort risk equations to personalize atherosclerotic cardiovascular disease risk assessment in primary prevention. In this review, we discuss the rationale and evidence behind each of the risk- enhancing factors to help clinicians perform a more personalized cardiovascular risk assessment. The risk-enhancing factors are high-risk features that may guide the use of lipid-lowering therapy particularly in intermediate and select borderline risk patients. For the purpose of this review, these factors are divided into 5 categories: (i) race and genetics, (ii) conditions specific to women (iii) lipid related risk, (iv) concurrent high-risk medical conditions, and (v) biomarkers. The addition of the risk-enhancing factors to the pooled cohort equations provides a more individualized and comprehensive approach to cardiovascular disease risk assessment.

Steno-Stiffness Approach for Cardiovascular Disease Risk Assessment in Primary Prevention.

Steno-Stiffness Approach for Cardiovascular Disease Risk Assessment in Primary Prevention.

Effect of using cardiovascular risk scoring in routine risk assessment in primary prevention of cardiovascular disease: an overview of systematic reviews

BackgroundOur objectives were to critically appraise and summarise the current evidence for the effectiveness of using cardiovascular disease (CVD) risk scoring (total risk assessment - TRA) in routine risk assessment in primary prevention of CVD compared with standard care with regards to patients outcomes, clinical risk factor levels, medication prescribing, and adverse effects.MethodsWe carried out an overview of existing systematic reviews (SRs). Presentation of the results aligned guidelines from the PRISMA statement. The data is presented as a narrative synthesis. We searched MEDLINE (Ovid), EMBASE, CENTRAL and SCOPUS databases from January 1990 to March 2017, reviewed the reference lists of all included SRs and searched for ongoing SRs in PROSPERO database. We encompassed SRs and meta-analyses which took into account RCTs, quasi-RCTs, and observational studies investigating the effect of using CVD risk scoring. Only studies performed in a primary care setting, with adult participants free of clinical CVD were eligible. Intervention was CVD risk assessment with use of the total CVD risk scoring compared with standard care with no use of TRA .ResultsWe identified 2157 records, we then recognised and analysed 10 relevant SRs. One SR reported statistically insignificant reduction of CVD death, when using TRA, the second SR presented meta-analysis which reported no effect on fatal and non-fatal CV events compared with conventional care (5.4% vs 5.3%; RR 1.01, 95% CI 0.95 to 1.08; I2 = 25%). Three SRs have shown that using TRA causes no adverse events. The impact of TRA on global CVD risk as well as individual risk factors is ambiguous, but a tendency towards slight reduction of blood pressure, total cholesterol and smoking levels, especially in high risk patient groups was observed. TRA had no influence on lifestyle behaviour.ConclusionsThere is limited evidence, of low overall quality, suggesting a possible lack of effectiveness of TRA in reducing CVD events and mortality, as well as a clinically insignificant influence on individual risk factor levels. Using TRA does not cause harm to patients.Trial registrationSystematic review protocol was registered with the International PROSPERO database - registration number CRD42016046898.

Weighted Multi-marker Genetic Risk Scores for Incident Coronary Heart Disease among Individuals of African, Latino and East-Asian Ancestry

We examined the clinical utility of two multi-locus genetic risk scores (GRSs) previously validated in Europeans among persons of African (AFR; n = 2,089), Latino (LAT; n = 4,349) and East-Asian (EA; n = 4,804) ancestry. We used data from the GERA cohort (30–79 years old, 68 to 73% female). We utilized two GRSs with 12 and 51 SNPs, respectively, and the Framingham Risk Score (FRS) to estimate 10-year CHD risk. After a median 8.7 years of follow-up, 450 incident CHD events were documented (95 in AFR, 316 in LAT and 39 EA, respectively). In a model adjusting for principal components and risk factors, tertile 3 vs. tertile 1 of GRS_12 was associated with 1.86 (95% CI, 1.15–3.01), 1.52 (95% CI, 1.02–2.25) and 1.19 (95% CI, 0.77–1.83) increased hazard of CHD in AFR, LAT and EA, respectively. Inclusion of the GRSs in models containing the FRS did not increase the C-statistic but resulted in net overall reclassification of 10% of AFR, 7% LAT and EA and in reclassification of 13% of AFR and EA as well as 10% LAT in the intermediate FRS risk subset. Our results support the usefulness of incorporating genetic information into risk assessment for primary prevention among minority subjects in the U.S.

Prognostic role of cardiac calcifications in primary prevention: A powerful marker of adverse outcome highly dependent on underlying cardiac rhythm

BackgroundIncreasing evidence exists regarding calcium detected in aortic cusps and/or mitral annulus (AOC_MAC) at transthoracic echocardiogram as a predictor of cardiovascular (CV) events and mortality. PurposeTo verify whether AOC_MAC has a prognostic role in the setting of primary prevention independently of the presence of atrial fibrillation (AF). MethodsAll subjects consecutively referred from January 2011 to October 2014 to the Cardiovascular Centre for CV risk assessment in primary prevention were selected. AOC_MAC was assessed by transthoracic echocardiography. Primary study endpoint was a composite of CV hospitalizations/all-cause death. ResultsThe 1389 study patients were 70 years old, 43% males, 24% had diabetes mellitus, 75% arterial hypertension, 56% dyslipidaemia. Of all, 997 (72%) were in sinus rhythm (SR), 392 (28%) in AF. Patients with AF were older and more frequently males, with larger atria than SR subjects. During a median follow-up of 32 months, 165 patients (12%) were hospitalized for CV cause, 68 (5%) died. The primary endpoint occurred more frequently in patients with than without AOC_MAC (18% vs 11%, p < 0.001). AF patients showed higher event-rate compared with patients in SR (20% vs 10%, respectively; p < 0.01). AOC_MAC emerged as an independent prognosticator of primary endpoint in SR patients (HR 1.74 [1.07–2.82], p = 0.02), together with increasing age and left ventricular hypertrophy, while AOC_MAC had no prognostic relevance in AF patients. ConclusionsIn subjects with multiple CV risk factors assessed in primary prevention, the presence of AF nullifies the prognostic power of AOC_MAC, on the contrary robustly confirmed in SR patients.

Effect of using cardiovascular risk scoring in routine risk assessment in primary prevention of cardiovascular disease: protocol for an overview of systematic reviews

IntroductionMajor clinical practice guidelines recommend assessing risk of cardiovascular disease (CVD) using absolute/global/total CVD risk scores. However, the effectiveness of using them in clinical practice, despite publication of numerous randomised...

Systematic versus opportunistic risk assessment for primary prevention of cardiovascular disease

Systematic versus opportunistic risk assessment for primary prevention of cardiovascular disease

Utility of repeat serum cholesterol measurements for assessment of cardiovascular risk in primary prevention.

Measurement of total cholesterol is part of cardiovascular disease risk assessment in primary prevention. Frequently, old total cholesterol values are available. We assessed whether previously measured total cholesterol values could be used to estimate cardiovascular disease risk in primary prevention. A longitudinal analysis using data of a population-based prospective cohort study (Study of Health in Pomerania) over a period of 10 years. Altogether, 1112 subjects (45% male, mean age 57.8 years, SD ± 6.8 years) without prior history of myocardial infarction or stroke were included. We calculated diagnostic test properties for SCORE-Germany estimates using 5- and 10-year-old total cholesterol values to predict high (≥5%) cardiovascular disease risk using estimates based on current total cholesterol as a gold standard. Mean total cholesterol decreased from 5.88 mmol/l (SD ± 1.21) at baseline to 5.73 mmol/l (SD ± 1.10) after 10 years. A high cardiovascular disease risk was found in 3.2% of subjects at baseline, in 4.9% after 5 years and in 16.2% after 10 years based on current total cholesterol values. SCORE-estimates using 5-year-old total cholesterol had a sensitivity of 90.9% (95% confidence interval 87.7-94.1) and specificity of 97.2% (95% confidence interval 96.4-98.0). For 10-year-old total cholesterol, sensitivity was 94.2% (95% confidence interval 91.6-96.8) and specificity 96.3% (95% confidence interval 95.3-97.2). We observed only minor changes of total cholesterol over time. SCORE-estimates using 5- or 10-year-old total cholesterol had a high sensitivity, specificity and test accuracy to identify subjects at high cardiovascular disease risk and resulted in low misclassification rates.

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Putting it into Perspective: Multimarker Panels for Cardiovascular Disease Risk Assessment

Cardiovascular biomarkers started as tools to aid with specific medical diagnoses, but are now being used broadly for screening, prognosis and monitoring of multiple diseases. Novel markers that reflect important pathophysiologic pathways are emerging regularly, although each new set of markers introduced raises many questions on how best to utilize them to improve patient outcomes. One promising approach for getting the most out of cardiovascular biomarkers is to combine multiple markers together into a multimarker panel. When each marker represents a distinct pathophysiologic pathway, the combined panel has advantages over individual biomarkers and may be useful when used in specific clinical scenarios for assessing risk, improving diagnosis or directing individualized therapy. This perspective article highlights several of the most promising biomarkers and strategies for achieving improved cardiovascular risk assessment for primary prevention of cardiovascular disease via multimarker panels.

Assessment of subclinical atherosclerosis by carotid intima media thickness: technical issues

Carotid intima-media thickness assessed by ultrasonography of carotid arteries is a safe, non-expensive, feasible and accurate method for detecting early signs of atherosclerosis and carotid intima-media thickness and change in carotid intima-media thickness over time reflect cardiovascular disease risk. Technical aspects impact on the measurement, variability and interpretation of carotid intima-media thickness. These include device aspects, inter- and intra-sonographer variability and the ultrasound protocol used. The mean common carotid intima-media thickness and the mean maximum common carotid intima-media thickness are the most widely used carotid intima-media thickness measurements. Common carotid intima-media thickness values of around 0.5 mm are considered 'normal' in young adults. Values are higher in men than in women, in African-Americans than Caucasians and increase with age. Carotid intima-media thickness values at or above the 75th percentile of a reference population indicate increased cardiovascular risk. Guidelines differ in their recommendations for the use of carotid intima-media thickness measurements for risk assessment in primary prevention because evidence suggesting that it improves upon conventional risk scores is inconsistent. Carotid intima-media thickness is frequently used in clinical trials as a surrogate endpoint for cardiovascular events on the assumption that regression or slowed progression of carotid intima-media thickness, induced by cardiovascular risk interventions, reflects a reduction in cardiovascular events. However, further data are required to confirm this linear relationship. No international guidelines exist on the use of carotid intima-media thickness as a research tool. Quality control in acquisition, measurement and interpretation of carotid intima-media thickness are important considerations and the carotid intima-media thickness protocol used should be determined by the research question under investigation.

Circulating Troponin As Measured by a Sensitive Assay for Cardiovascular Risk Assessment in Primary Prevention

Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. We measured circulating concentrations of cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardiovascular events (MACE) during 5 years of follow-up. Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.

Biomarkers and Cardiovascular Risk Assessment for Primary Prevention: An Update

Interest in cardiovascular biomarkers in primary prevention has increased dramatically in the past decade. This increase has been fueled by an improved understanding of cardiovascular pathophysiology, as well as novel technologies for biomarker identification. In this review we provide a brief overview of recent concepts in the evaluation of screening biomarkers, because biomarkers may behave differently when used for screening as opposed to diagnosis or disease staging. The following specific biomarker examples are then discussed, with a focus on data from primary prevention studies: high-sensitivity C-reactive protein, B-type natriuretic peptide, lipoprotein-associated phospholipase A2, and high-sensitivity troponin T. The article concludes by addressing novel platforms for biomarker discovery, reviewing recent examples from the field of metabolomics. An ongoing challenge is to develop screening strategies that can identify individuals at risk for cardiovascular events well before symptoms appear. For this purpose, the measurement of soluble biomarkers could be an important adjunct to traditional cardiovascular risk assessment. Recent studies highlight both the strengths and limitations of "novel" circulating biomarkers, and suggest that substantial work is still needed to identify biomarkers that are sufficiently accurate and cost-effective for routine use in primary prevention.