Atherosclerosis

Risk Factors and Atherogenesis

Atherosclerosis

Atherosclerotic lesions and overall cardiovascular risks

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Go to top of page. Objectives The goal of this study was to investigate whether complex aortic atherosclerosis is associated with increased risk of vascular events in a non-selected population. Background In selected high-risk patients, aortic atherosclerosis is associated with increased risk of vascular events. Results At five-year median follow-up range, 0. Age, male gender, prior coronary artery disease, higher pulse pressure, and diabetes were significant cardiovascular predictors.

Age, prior myocardial infarction, and a history of atrial fibrillation were significant cerebrovascular predictors. Simple aortic plaques persons were not independently associated with either cardiac or cerebrovascular events. Complex plaques 44 persons were marginally associated with cardiac events, adjusting for age and gender hazard ratio [HR], 2.

Complex plaques were associated with cerebrovascular events only univariately. Conclusions Aortic atherosclerotic plaques are not associated with future cardiac or cerebrovascular events. Aortic atherosclerosis may not be an independent risk factor for vascular events in the general population. High-resolution imaging afforded by transesophageal echocardiography TEE has facilitated the diagnosis and severity grading of aortic atherosclerosis.

With the paradigm shift from secondary to primary prevention of stroke, this tool is increasingly applied in the evaluation of risk of stroke and cardiovascular disease, atherosclerotic lesions and overall cardiovascular risks. Aortic atherosclerosis is well known to increase with advancing age. Despite the many studies reporting an association between aortic atherosclerosis and increased cardiovascular and stroke morbidity and mortality 13this relationship remains undefined because of the highly selected nature of TEE patients, atherosclerotic lesions and overall cardiovascular risks, most with prior strokes, and the variable adjustment for the effects of age and other comorbid conditions.

Assessment of Risk in a Community SPARC cohort was established in to identify risk factors for cerebral ischemia and cardiovascular disease in the population. The cohort is unique in that it provides comprehensive TEE data on the prevalence of aortic atherosclerosis in a cohesive random sample of the population with comprehensive follow-up 4,5.

This report assesses the impact of aortic atherosclerosis as an independent risk factor for subsequent cardiovascular and atherosclerotic lesions and overall cardiovascular risks events in a population-based sample. The resources of the Rochester Epidemiology Project in Rochester, Minnesota, were used to enumerate the Olmsted Dimetapp allergy and cold population 45 years old or older.

Of the 1, residents initially sampled, atherosclerotic lesions and overall cardiovascular risks, were ineligible by predetermined exclusion criteria terminal illness, dementia precluding informed consent, severe disability, or esophageal disease precluding TEEand declined to participate. The final SPARC sample consisted of randomly sampled subjects about one-half of those eligiblewho consented to multimodality testing, including medical record review, home medical interview, TEE, carotid ultrasonography, and repeated blood pressure measurements.

End point catapres and drug tests were prespecified before initiation of the study, and updated information was obtained from the medical records of these subjects five years after the original SPARC assessment. Three of the patients declined authorization for medical research under Minnesota statute A comparison of comorbid conditions, age, and gender among participants and a random sample of eligible non-participants decliners demonstrated no significant differences, thus confirming that participants were a representative sample of atherosclerotic lesions and overall cardiovascular risks population 5.

Baseline transthoracic animals and cancer patients and atherosclerotic lesions and overall cardiovascular risks TEE 6 were conducted according to standard practice guidelines using commercially available ultrasonographic instruments. The ascending aorta, aortic arch, and descending aorta were imaged in short- and long-axis views. Atherosclerosis was defined as irregular intimal thickening with increased echogenicity.

Atherosclerotic plaques were defined as complex in the presence of protruding atheroma atherosclerotic lesions and overall cardiovascular risks than 4-mm thick 4,79mobile debris, or plaque ulceration, and as simple for plaques lacking these morphologic features in any aortic segment.

Cardiac events included death, non-fatal myocardial infarction, heart failure associated with coronary atherosclerotic lesions and overall cardiovascular risks disease CADand coronary revascularization bypass surgery, angioplasty.

Cerebrovascular events referred to deaths related to cerebrovascular disease CVDischemic strokes, and transient ischemic attacks TIA. Survival free of cardiac events or cerebrovascular events was estimated by the Kaplan-Meier product-limit method, starting at the initial SPARC visit. Patients were censored at the last medical visit if they were lost to follow-up two patientsat the date of the medical record abstraction, or at the date of death if death was not due to CAD or CVD.

Cumulative incidence 10 was calculated to account for the competing risks of cardiac event, cerebrovascular event, or death. Expected survival was calculated using the cohort method and the Minnesota State Life Tables The Cox atherosclerotic lesions and overall cardiovascular risks hazards regression was used to model the role of clinical risk factors for cardiovascular and cerebrovascular events. Univariate models, age- and gender-adjusted models, and, finally, stepwise and backward multivariate models, adjusting for age and male gender, were used to determine the final subset of risk factors for each end point.

A p value of 0. All the variables presented in Table 1 ,except the aortic plaque variables assessed at a later stage of the analysis and total cholesterol data available in a subset of subjectswere considered for both the univariate and stepwise modeling.

Pulse pressure was highly correlated with systolic and diastolic blood pressure, resulting in problems of multicolinearity. Thus, two versions of the stepwise process were run, one version with pulse pressure as the blood pressure variable and one version with the systolic and diastolic blood pressure variables.

Only the pulse pressure results are reported the same variables were in the models using systolic and diastolic blood pressure. The functional forms of all the continuous variables were examined, and no transformations were deemed necessary. Two-way interactions in the final stepwise models were explored.

The relationships among aortic atherosclerosis and the CAD and CVD end points were examined univariately unadjustedadjusting for age and gender, and adjusting for all variables in the respective risk factor models. Atherosclerosis was defined using all three segments ascending, arch, or descending and again separately using only two segments ascending or arch. All atherosclerotic lesions and overall cardiovascular risks among the atherosclerosis and risk factor variables were assessed to determine if they jointly entered the model.

The proportional hazards assumption was examined for the atherosclerosis variable and for the final multivariate models for each end point. Table 1 summarizes the atherosclerosis risk factors, comorbid conditions, and atherosclerotic plaques present at baseline and used in the stepwise age- and gender-adjusted multivariate analysis.

Mean age was Simple and complex aortic plaques were detected in at least one of the three aortic segments in Cardiac events occurred in 95 persons 31 myocardial infarctions, 40 cardiac failures, 16 coronary revascularizations, 8 cardiac deathsand cerebrovascular events occurred in 41 persons 20 strokes, 21 TIA.

Eighteen persons had both a cardiac event and a cerebrovascular event. Nineteen persons died before having either; their data were censored. Of persons, had no qualifying event and were alive at the date of censor. Two cases were lost to follow-up and were censored.

Mean follow-up was five years 0. The cumulative incidence of cardiac end points was 3. Results of the univariate analyses are presented in Table 2. Each year increase in age increased the hazard two-fold. The Kaplan-Meier product-limit estimates by age quartiles Fig. Table 3 presents the same variables adjusted for age and gender. As reported in Table 4 ,increasing age, male gender, prior CAD, and higher pulse pressure were jointly associated with cardiac events. Univariately, atherosclerosis grade using all three segments or two of the three segments was associated with cardiac events.

The hazard ratios HR using all three segments were 3. The Kaplan-Meier product-limit estimates of atherosclerosis grade Fig. After adjustment for age and gender, atherosclerotic lesions and overall cardiovascular risks, the HR for simple atherosclerosis versus no atherosclerosis did not differ significantly from 1. After adjustment for additional clinical risk atherosclerotic lesions and overall cardiovascular risks in the multivariate analysis, atherosclerotic lesions and overall cardiovascular risks, complex atherosclerosis using either definition was not associated significantly with an increased risk of cardiac events Table 5.

The cumulative incidence of cerebrovascular end points was 1. Kaplan-Meier product-limit curves illustrate this univariate association of age with cerebrovascular events Fig. Older compare razadyne and aricept, prior myocardial infarction, and a history of atrial fibrillation were predictors of cerebrovascular events in a multivariate model Table 4.

Univariately, atherosclerosis grade using either definition was associated with cerebrovascular events as illustrated by the Kaplan-Meier product-limit curves Fig. After adjustment for age and gender, neither simple nor complex atherosclerosis remained significantly associated with outcome Table 5. After additional adjustment for other clinical risk factors, atherosclerosis was not significantly associated with outcome Table 5. The proportional hazards assumption was met in the univariate models of simple and complex atherosclerosis versus no atherosclerosis for each end point, which indicates that subjects who had atherosclerosis were not more likely to experience earlier events than were subjects without atherosclerosis data not shown.

In this population-based study, a detailed analysis of multiple variables led to the following conclusions:. Although highly significant in the univariate analysis, aortic atherosclerosis of clomid and egg quaility severity, after adjustment for age and other risk factors, was not an independent predictor of cardiac events or stroke. Several atherosclerotic risk factors age, male gender, higher pulse pressure, atherosclerotic lesions and overall cardiovascular risks, and diabetes are significant independent predictors of cardiac events.

Age, prior myocardial infarction, and atrial fibrillation are predictive of cerebrovascular events. In that atherosclerosis is a diffuse process, it is not surprising that multiple studies have found an association between aortic atherosclerosis and CAD. Extrapolation of these studies to the general population is misleading.

Most studies described patients with prior embolic events, predominantly strokes. In contrast, the current study enabled us to assess aortic anatomy and multiple risk factors in a large non-referred population representative of the general population in a well-defined geographic area.

Several authors have shown a strong association between aortic atherosclerosis and other risk factors for stroke. Age, hypertension, atrial fibrillation, carotid artery disease, and diabetes mellitus are well-known risk factors for cardiac events and stroke 21 A recent study from our group confirmed the strong association of aortic atherosclerosis with hypertension and CAD in the general population 9, These findings challenge previously drawn conclusions about the cause-and-effect relationship of aortic atherosclerosis and clinical outcome.

Age has been shown to be a strong independent predictor of aortic atherosclerosis 8which suggests that atherosclerosis may be a marker of aging rather than a true risk factor for stroke. One autopsy study concluded that the presence of moderate or severe aortic atherosclerosis did not predict ischemic stroke subtype Complex atherosclerosis is a high-risk marker in high-risk patients, but it is also a marker of many other risk factors for stroke, so a cause-and-effect relationship cannot be established.

The current prospective analysis had the advantage that the CAD event was known to have occurred after the TEE assessment, atherosclerotic lesions and overall cardiovascular risks. The prospective analysis examined atherosclerosis in all patients who had CAD, including those who died because of it a small percentage of total CAD events. Of necessity, the retrospective analysis examined atherosclerosis in patients with CAD before assessment who survived long enough to enter our study.

Death rates in the overall SPARC I cohort, including those with or without atherosclerosis, were about one-half of what was expected for the Minnesota white atherosclerotic lesions and overall cardiovascular risks. A comparison of respondents and non-respondents in an Olmsted County study of osteoporosis found similar death rates Because expected rates are based on the entire population, including those too ill to be eligible, this finding is not surprising their survival is poor and is a concern common observational studies and clinical trials.

Considered jointly, atherosclerotic lesions and overall cardiovascular risks, the retrospective and prospective studies suggest that although atherosclerosis increases with age as does the risk of CADit does not in itself result in an increased risk for CAD.

However, size limitations imposed by the use of an invasive study in a relatively healthy population sample may have limited the ability of the SPARC study to detect a statistically significant hazard for the less prevalent risk factors. With a larger sample size, the wide CIs around the adjusted HR for simple and complex atherosclerosis three segments would narrow, but would still likely be atherosclerotic lesions and overall cardiovascular risks around 1.

Nevertheless, we cannot exclude the possibility that the hazard due to complex atherosclerosis compared with no atherosclerosis may be as high as 2.

 

Atherosclerotic lesions and overall cardiovascular risks

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