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Lipoprotein(a) and Subclinical Vascular and Valvular Calcification on Cardiac Computed Tomography: The Atherosclerosis Risk in Communities Study.

ABSTRACT: Background Lipoprotein(a) (Lp(a)) is a potent causal risk factor for cardiovascular events and mortality. However, its relationship with subclinical atherosclerosis, as defined by arterial calcification, remains unclear. This study uses the ARIC (Atherosclerosis Risk in Communities Study) to evaluate the relationship between Lp(a) in middle age and measures of vascular and valvular calcification in older age. Methods and Results Lp(a) was measured at ARIC visit 4 (1996-1998), and coronary artery calcium (CAC), together with extracoronary calcification (including aortic valve calcium, aortic valve ring calcium, mitral valve calcification, and thoracic aortic calcification), was measured at visit 7 (2018-2019). Lp(a) was defined as elevated if >50 mg/dL and CAC/extracoronary calcification were defined as elevated if >100. Logistic and linear regression models were used to evaluate the association between Lp(a) and CAC/extracoronary calcification, with further stratification by race. The mean age of participants at visit 4 was 59.2 (SD 4.3) years, with 62.2% women. In multivariable adjusted analyses, elevated Lp(a) was associated with higher odds of elevated aortic valve calcium (adjusted odds ratio [aOR], 1.82; 95% CI, 1.34-2.47), CAC (aOR, 1.40; 95% CI, 1.08-1.81), aortic valve ring calcium (aOR, 1.36; 95% CI, 1.07-1.73), mitral valve calcification (aOR, 1.37; 95% CI, 1.06-1.78), and thoracic aortic calcification (aOR, 1.36; 95% CI, 1.05-1.77). Similar results were obtained when Lp(a) and CAC/extracoronary calcification were examined on continuous logarithmic scales. There was no significant difference in the association between Lp(a) and each measure of calcification by race or sex. Conclusions Elevated Lp(a) at middle age is significantly associated with vascular and valvular calcification in older age, represented by elevated CAC, aortic valve calcium, aortic valve ring calcium, mitral valve calcification, thoracic aortic calcification. Our findings encourage assessing Lp(a) levels in individuals with increased cardiovascular disease risk, with subsequent comprehensive vascular and valvular assessment where elevated.

SUBMITTER: Obisesan OH

PROVIDER: S-EPMC9238743 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In the last decades, significant advances have been made in the preventive approaches to cardiovascular disease. Even so, coronary artery disease remains one of the main causes of morbidity and mortality worldwide. Invasive imaging modalities, such as intravascular ultrasound or optical coherence tomography, have played a key role in the comprehension of the pathological processes underlying myocardial infarction and cerebrovascular disease. These imaging techniques have contributed greatly to the identification and phenotyping of the culprit lesion, the so-called vulnerable plaque. Coronary computed tomographic angiography (CCTA) has emerged in more recent years as the non-invasive modality of choice in the study of coronary atherosclerosis, showing in many studies a diagnostic yield comparable to invasive approaches. Moreover, being able to describe extra-luminal characteristics of the affected vessel, CCTA has greatly contributed towards shifting the attention of researchers from the mere quantification of luminal stenosis to the identification of adverse plaque features, which appear to have a stronger prognostic value. However, the identification of some of the hallmarks of vulnerable plaques is qualitative in nature and, therefore, subject to some degree of inter-reader variability. Moreover, CCTA is still unable to identify some fine markers of plaque vulnerability which can be detected by invasive techniques, such as neovascularization and plaque erosion, among others. Nonetheless, radiological images can be viewed as vast 3-D datasets which, via the use of recent technology, allow for the extraction of numerous quantitative features that may be used to accurately phenotype a given lesion. Radiomics is the process of extrapolating innumerable parameters from a given region of interest, with the goal of establishing correlations between quantitative variables and clinical data. These datasets can then be manipulated to create predictive models via the use of automated algorithms in a process called machine learning. As a result of these approaches, radiological images may offer information regarding the characterization of a plaque which can go much beyond the boundaries of what can be qualitatively asserted by the human eye, contributing to expanding the knowledge of the disease and ultimately assist clinical decisions. Thus far, radiomics has found its more consistent area of application in the field of oncology; to present date, the amount of clinical data regarding coronary artery disease is still relatively small, partly due to the technical difficulties associated with the implementation of such techniques to the study of a small and geometrically complex lesion such as the coronary plaque. The present review, after a summary of the imaging modalities most commonly used nowadays in the study of coronary plaques, will provide a perspective on the application of radiomic analysis to coronary artery disease.

Project description:BackgroundWhether high burden of subclinical vascular disease (SVD) is associated with increased premature mortality among middle-aged adults is not adequately understood. The association of midlife SVD burden with premature mortality among middle-aged adults free of clinical cardiovascular disease (CVD) could provide further insights into stratifying premature death beyond clinical CVD.ObjectiveTo determine whether high burden of subclinical vascular disease is associated with increased premature mortality among middle-aged adults.DesignWe leveraged data from the Atherosclerosis Risk in Communities Study.ParticipantsThirteen thousand eight hundred seventy-six community-dwelling blacks and whites aged 45-64 years from the Atherosclerosis Risk in Communities Study.Main measuresEach SVD measure-ankle-brachial index, carotid intima-media thickness, and electrocardiogram-was scored 0 (no abnormalities), 1 (minor abnormalities), or 2 (major abnormalities). An index was constructed as the sum of three measures, ranging from 0 (lowest burden) to 6 (highest burden). We used the Cox proportional-hazards model to determine the association of SVD burden with premature mortality (death before age 70) among persons free of clinical CVD. We then tested the difference in point estimates between SVD and clinical CVD.Key resultsAmong persons without CVD, the premature death was 1.7, 2.1, 2.5, and 3.8 per 1000 person-years among those with an SVD score of 0 (lowest burden), 1, 2, and 3-6 (highest burden), respectively. After multivariable-adjustment, highest SVD burden (score = 3-6; HR = 1.47) was significantly associated with premature death among persons initially without CVD. In the model where persons with and without CVD were included, high SVD burden (score: 3-6 vs. 0) and CVD did not have hugely different association with premature death (HR = 1.49 vs. 1.68; P = 0.32 for comparison).ConclusionsMidlife SVD burden was associated with premature mortality and it could stratify premature death beyond clinical CVD. It is important to take SVD into account when designing interventions for reducing premature mortality.

Project description:IntroductionVascular calcification and stiffness are associated with higher mortality and cardiovascular disease in hemodialysis patients, but the underlying mechanism is not well elucidated and previous studies have been contradictory. We sought to determine the association of circulating calcification biomarkers with calcification, stiffness, and mortality in a multiethnic incident dialysis population.MethodsAmong 391 incident hemodialysis participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, we examined the cross-sectional associations of baseline fibroblast growth factor 23 (FGF23), desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, and osteoprotegerin (OPG) according to total coronary artery calcium score (CAC, using the Agatston calcification criteria) at baseline, vascular stiffness (pulse wave velocity [PWV]) over 4 study visits, and all-cause mortality.ResultsPatients' mean age was 55 years; 40% were female, 72% were African American, and 58% had diabetes. Higher OPG and FGF23 were associated with a 1.09-fold (per 5-pmol/l increase in OPG; 95% confidence interval [CI]: 1.01-1.17) and 1.12-fold (per increase of 100 log RU/ml in FGF23; 95% CI: 1.02‒1.34) higher prevalence of CAC, independent of demographics, comorbidities, dialysis factors, and serum klotho levels. Higher OPG was associated with higher baseline PWV. Higher FGF23 was associated with lower PWV over follow-up. dp-ucMGP and fetuin-A were not associated with either CAC or vascular stiffness. After adjustment, circulating biomarkers were not associated with mortality risk.ConclusionSeveral circulating calcification biomarkers were only modestly associated with subclinical cardiovascular disease in an incident multiethnic hemodialysis population; none were associated with mortality. Understanding whether these associations persist in larger, diverse hemodialysis populations is warranted before planning trials.

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Lipoprotein(a) and Subclinical Vascular and Valvular Calcification on Cardiac Computed Tomography: The Atherosclerosis Risk in Communities Study.

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