Low-risk lifestyle, coronary calcium, cardiovascular events, and mortality: results from MESA.
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SUBMITTER: Ahmed HM
PROVIDER: S-EPMC3698994 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThere are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations.MethodsOur study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk).ResultsCompared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups.ConclusionsIndividuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.
| S-EPMC8058297 | biostudies-literature
Project description:Low-dose rivaroxaban was effective in secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the COMPASS trial. There is no established role, however, for oral anticoagulants in primary prevention. We evaluated whether coronary artery calcium (CAC) scoring identifies a high-risk primary prevention adult population who may benefit from low-dose rivaroxaban to prevent ASCVD events. We modeled expected outcomes of low-dose rivaroxaban in 5,196 Multiethnic Study of Atherosclerosis (MESA) cohort participants not already on antiplatelet or anticoagulant therapy. We applied relative risk ratios from COMPASS to absolute MESA event rates in order to estimate number needed to treat (NNT) to avoid a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, as well as number needed to harm (NNH) to cause 1 hospitalized bleed; with both NNT and NNH stratified by calculated ASCVD risk and by baseline CAC. MESA participants with CAC ?300 had crude ASCVD event rate of 20 per 1000 patient-years, which is comparable to that observed in the COMPASS control-arm. CAC was independently associated with the composite ASCVD outcome (p <0.001 for trend). However, CAC was not independently associated with adjusted hazard ratio for hospitalized major bleeding. Predicted 5-year NNT (modeled from COMPASS) was 75 in persons with CAC 100-299 and 45 with CAC ?300 despite NNH values of 252 and 98, respectively. In conclusion, CAC helps to distinguish estimated ASCVD benefit from estimated bleeding harm, thereby identifying very high-risk primary prevention adults without established cardiovascular disease who may derive net-benefit from low-dose rivaroxaban.
| S-EPMC6755041 | biostudies-literature
Project description:AimsWhile coronary artery calcium (CAC) has been extensively validated for predicting clinical events, most outcome studies of CAC have evaluated coronary heart disease (CHD) rather than atherosclerotic cardiovascular disease (ASCVD) events (including stroke). Also, virtually all CAC studies are of short- or intermediate-term follow-up, so studies across multi-ethnic cohorts with long-term follow-up are warranted prior to widespread clinical use. We sought to evaluate the contribution of CAC using the population-based MESA cohort with over 10 years of follow-up for ASCVD events, and whether the association of CAC with events varied by sex, race/ethnicity, or age category.Methods and resultsWe utilized MESA, a prospective multi-ethnic cohort study of 6814 participants (51% women), aged 45-84 years, free of clinical CVD at baseline. We evaluated the relationship between CAC and incident ASCVD using Cox regression models adjusted for age, race/ethnicity, sex, education, income, cigarette smoking status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes, lipid-lowering medication, systolic blood pressure, antihypertensive medication, intentional physical exercise, and body mass index. Only the first event for each individual was used in the analysis. Overall, 500 incident ASCVD (7.4%) events were observed in the total study population over a median of 11.1 years. Hard ASCVD included 217 myocardial infarction, 188 strokes (not transient ischaemic attack), 13 resuscitated cardiac arrest, and 82 CHD deaths. Event rates in those with CAC = 0 Agatston units ranged from 1.3% to 5.6%, while for those with CAC > 300, the 10-year event rates ranged from 13.1% to 25.6% across different age, gender, and racial subgroups. At 10 years of follow-up, all participants with CAC > 100 were estimated to have >7.5% risk regardless of demographic subset. Ten-year ASCVD event rates increased steadily across CAC categories regardless of age, sex, or race/ethnicity. For each doubling of CAC, we estimated a 14% relative increment in ASCVD risk, holding all other risk factors constant. This association was not significantly modified by age, sex, race/ethnicity, or baseline lipid-lowering use.ConclusionsCoronary artery calcium is associated strongly and in a graded fashion with 10-year risk of incident ASCVD as it is for CHD, independent of standard risk factors, and similarly by age, gender, and ethnicity. While 10-year event rates in those with CAC = 0 were almost exclusively below 5%, those with CAC ≥ 100 were consistently above 7.5%, making these potentially valuable cutpoints for the consideration of preventive therapies. Coronary artery calcium strongly predicts risk with the same magnitude of effect in all races, age groups, and both sexes, which makes it among the most useful markers for predicting ASCVD risk.
| S-EPMC6030975 | biostudies-literature
Project description:BackgroundThe JUPITER trial showed that some patients with LDL-cholesterol concentrations less than 3·37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more benefit from treatment with rosuvastatin, although absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values.Methods950 participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all criteria for JUPITER entry. We compared coronary heart disease and cardiovascular disease event rates and multivariable-adjusted hazard ratios after stratifying by burden of CAC (scores of 0, 1-100, or >100). We calculated 5-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC strata.FindingsMedian follow-up was 5·8 years (IQR 5·7-5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99-9·25) for coronary heart disease, and of 2·57 (1·48-4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment.InterpretationCAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with measurable atherosclerosis could allow for more appropriate allocation of resources.FundingNational Institutes of Health-National Heart, Lung, and Blood Institute.
| S-EPMC3173039 | biostudies-literature
Project description:Highlights • Women with early menopause are at greater risk for heart disease over the long-term.• Over half of middle-aged women with early menopause were free of CAC, similar to women without early menopause.• Coronary calcium scores were similar between women with and without early menopause.• Women without calcium had low risk for heart disease regardless of menopause history. Background and Aims We aimed to determine the utility of coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk stratification in women with and without early menopause (EM). Methods To examine the association between CAC and incident ASCVD, we performed Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling using data from 2,456 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) with or without EM, defined as occurring at <45 years of age. Results The cohort was 64.1 ± 9.1 years old and 28.0% experienced EM. There were 291 ASCVD events over 12.5 ± 3.6 year follow-up with a higher event rate among those with EM compared to those without EM of 13.6 vs. 9.0 per 1,000 year follow-up (p < 0.01). Women with EM had a slightly lower prevalence of CAC = 0 (55.1%) than women without EM (59.7%) (p = 0.04) despite no difference in mean age. Among women with CAC = 0, the cumulative incidence of ASCVD at 10 years was low-to-borderline for women with (5.4%) and without EM (3.2%) (p = 0.06). However, women with EM had a significantly higher 15-year risk with an adjusted HR of 1.96 (95% CI: 1.26–3.04). In multivariable Cox models, women with CAC ≥ 1 had progressively increased ASCVD risk that did not significantly differ by EM status. Conclusion In MESA, >50% of middle-aged postmenopausal women with EM had CAC = 0, similar to those without EM. Among women with CAC = 0, those with EM had a low to borderline 10-year risk of ASCVD, but the 15-year risk was significantly higher for women with EM versus those without EM. When CAC ≥ 1, the incidence of ASCVD was similar for women with and without EM. These findings support the use of CAC to help improve ASCVD risk stratification in women with EM. Condensed abstract This study investigated the association between coronary artery calcium (CAC) and incident atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women with and without early menopause (EM). We found that >50% of women had CAC = 0 and an associated low-to-borderline 10-year cumulative incidence of ASCVD. However, the risk for ASCVD was significantly higher for women with EM after 15-years follow-up. Additional research is needed to better understand the differences in long-term ASCVD risk between women with and without EM who have CAC = 0. Graphical abstract Image, graphical abstract
| S-EPMC9234594 | biostudies-literature
Project description:BACKGROUND:The coronary artery calcium (CAC) score predicts coronary heart disease (CHD) events, but methods for interpreting the score in combination with conventional CHD risk factors have not been established. METHODS AND RESULTS:We analyzed CAC scores and CHD risk factor measurements from 6757 black, Chinese, Hispanic, and white men and women aged 45 to 84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC was associated with age, sex, race/ethnicity, and all conventional CHD risk factors. Multivariable models using these factors predicted the presence of CAC (C statistic=0.789) and degree of elevation (16% of variation explained) and can be used to update a "pretest" CHD risk estimate, such as the 10-year Framingham Risk Score, that is based on an individual's conventional risk factors. In scenarios in which a high CAC score is expected, a moderately elevated CAC score of 50 is reassuring (eg, reducing risk from 10% to 6% in a healthy older white man), but when a low/zero CAC score is expected, even with identical pretest CHD risk, the same CAC score of 50 may be alarmingly high (eg, increasing risk from 10% to 20% in a middle-aged black woman with multiple risk factors). Both the magnitude and direction of the shift in risk varied markedly with pretest CHD risk and with the pattern of risk factors. CONCLUSIONS:Knowledge of what CAC score to expect for an individual patient, based on their conventional risk factors, may help clinicians decide when to order a CAC test and how to interpret the results.
| S-EPMC3840900 | biostudies-literature
Project description:ImportanceThe interplay of self-rated health (SRH), coronary artery calcium (CAC) scores, and cardiovascular risk is poorly described.ObjectivesTo assess the degree of correlation between SRH and CAC, to determine whether these measures are complementary for risk prediction, and to assess the incremental value of the addition of SRH to established risk tools.Design, setting, and participantsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a large population-based prospective cohort study of adults aged 45 to 84 years who were recruited from 6 US communities. A total of 6764 participants without baseline cardiovascular disease (CVD) were included in the analysis. Data were collected from July 2000 through August 2002. Follow-up was completed by December 2013, and data were analyzed from October 2018 to December 2018.ExposuresThe EVGGFP (excellent, very good, good, fair, and poor) self-assessment of overall health (assessed before the baseline study examination) and CAC score. The EVGGFP rating was categorized as poor/fair, good, very good, or excellent.Main outcomes and measuresHard coronary heart disease (CHD) events, hard CVD events, and all-cause mortality during a median follow-up of 13.2 years (interquartile range, 12.7-13.7 years).ResultsAmong the study population of 6764 participants, the mean (SD) age was 62.1 (10.2) years, and 52.9% were women. The EVGGFP rating was strongly associated with age, sex, race/ethnicity, educational and income levels, healthy diet and physical activity, and cardiovascular risk factors. Despite encapsulating many risk variables, no correlation (r = -0.007; P = .57) or association between EVGGFP and the presence (χ2 = 0.84; P = .84) or severity (χ2 = 4.64; P = .86) of CAC was found. During follow-up, 1161 deaths, 637 hard CVD events, and 405 hard CHD events were recorded. In models adjusted for age, sex, race/ethnicity, and CAC, participants who reported excellent health had a 45% lower risk of CVD (hazard ratio [HR], 0.55; 95% CI, 0.39-0.77) and a 42% lower risk of CHD (HR, 0.58; 95% CI, 0.37-0.90) compared with those who reported poor/fair health. Participants in the excellent SRH category who had any CAC had markedly elevated risk of hard CHD (HR, 6.19; 95% CI, 2.1-18.3) and CVD (HR, 6.50; 95% CI, 2.7-15.6) events compared with those with a CAC score of 0. The addition of the EVGGFP rating to CAC improved the area under the curve (C statistic) for CHD events (0.725 vs 0.734; P = .007), CVD events (0.693 vs 0.706; P < .001), and all-cause mortality (0.685 vs 0.707; P < .001). However, the addition of the EVGGFP rating to the combination of CAC and atherosclerotic CVD risk score did not significantly improve C statistics for CHD events (0.751 vs 0.753; P = .39), CVD events (0.739 vs 0.741; P = .18), or all-cause mortality (0.779 vs 0.781; P = .13).Conclusions and relevanceAlthough SRH and CAC integrate many risk variables, this study suggests that they are poorly correlated and have complementary predictive utility. A perception of excellent health does not obviate the need for definitive assessment of CVD risk, whereas fair/poor perceived health may serve as a risk enhancer, arguing for advanced risk assessment in selected clinical scenarios.
| S-EPMC6484585 | biostudies-literature
Project description:Studies suggest a link between vascular injuries and dementia. Only a few studies, however, examined a longitudinal relation of subclinical vascular disease with dementia. We tested whether baseline coronary artery calcium (CAC), a biomarker of subclinical vascular disease, is associated with incident dementia independent of vascular risk factors and APOE-ε4 genotype in a community-based sample. We analyzed 6293 participants of MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years at baseline (2000-2002), initially free of cardiovascular disease and noticeable cognitive deficit. Dementia cases were identified using hospital and death certificate International Statistical Classification of Diseases and Related Health Problems codes. Cox models were used to obtain hazard ratios according to CAC category, or per 1 SD log2[CAC+1], adjusted for vascular risk factor, APOE-ε4, with or without exclusion of interim stroke or cardiovascular disease. We observed 271 dementia cases in a median follow-up of 12.2 years. Baseline CAC had a graded positive association with dementia risk. Compared with no CAC, CAC score of 1 to 400, 401 to 1000, and ≥1001 had increased risk of dementia by 23%, 35%, and 71%, respectively, (Ptrend=0.026) after adjustment. 1 SD higher log2[CAC+1] was associated with 24% (95% confidence interval, 8%-41%; P=0.002) increase in dementia risk. Although the association was partially explained by interim stroke/cardiovascular disease, it remained significant even after excluding the interim events, or regardless of baseline age. Higher baseline CAC was significantly associated with increased risk of dementia independent of vascular risk factor, APOE-ε4, and incident stroke. This is consistent with a hypothesis that vascular injuries play a role in the development of dementia.
| S-EPMC5436307 | biostudies-literature
Project description:ObjectivesIn this study, we aimed to establish whether age-sex-specific percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes better than the actual (absolute) CAC score.BackgroundThe presence and extent of CAC correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events.MethodsMESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 asymptomatic participants followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled with Cox regression, and we compared models with percentiles based on age, sex, and/or race/ethnicity to categories commonly used (0, 1 to 100, 101 to 400, 400+ Agatston units).ResultsThere were 163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age- and sex-specific percentiles had significantly lower area under the receiver-operating characteristic curve (AUC) than when using absolute scores (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001). Akaike's information criterion indicated better model fit with the overall score. Both methods robustly predicted events (>90th percentile associated with a hazard ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score >400 associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-, sex-, and race/ethnicity-specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age-, sex-, and race/ethnicity-specific categories. Patients with low absolute scores are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank.ConclusionsUsing absolute CAC in standard groups performed better than age-, sex-, and race/ethnicity-specific percentiles in terms of model fit and discrimination. We recommend using cut points based on the absolute CAC amount, and the common CAC cut points of 100 and 400 seem to perform well.
| S-EPMC2652569 | biostudies-literature
Project description:BackgroundThe Multi-Ethnic Study of Atherosclerosis (MESA) showed that the addition of coronary artery calcium (CAC) to traditional risk factors improves risk classification, particularly in intermediate risk asymptomatic patients with LDL cholesterol levels <160 mg/dL. However, the cost-effectiveness of incorporating CAC into treatment decision rules has yet to be clearly delineated.ObjectiveTo model the cost-effectiveness of CAC for cardiovascular risk stratification in asymptomatic, intermediate risk patients not taking a statin. Treatment based on CAC was compared to (1) treatment of all intermediate-risk patients, and (2) treatment on the basis of United States guidelines.MethodsWe developed a Markov model of first coronary heart disease (CHD) and cardiovascular disease (CVD) events. We modeled statin treatment in intermediate risk patients with CAC?1 and CAC?100, with different intensities of statins based on the CAC score. We compared these CAC-based treatment strategies to a "treat all" strategy and to treatment according to the Adult Treatment Panel III (ATP III) guidelines. Clinical and economic outcomes were modeled over both five- and ten-year time horizons. Outcomes consisted of CHD and CVD events and Quality-Adjusted Life Years (QALYs). Sensitivity analyses considered the effect of higher event rates, different CAC and statin costs, indirect costs, and re-scanning patients with incidentalomas.ResultsWe project that it is both cost-saving and more effective to scan intermediate-risk patients for CAC and to treat those with CAC?1, compared to treatment based on established risk-assessment guidelines. Treating patients with CAC?100 is also preferred to existing guidelines when we account for statin side effects and the disutility of statin use.ConclusionCompared to the alternatives we assessed, CAC testing is both effective and cost saving as a risk-stratification tool, particularly if there are adverse effects of long-term statin use. CAC may enable providers to better tailor preventive therapy to patients' risks of CVD.
| S-EPMC4364761 | biostudies-literature