Carotid Plaque, Intima-Media Thickness, and Incident Aortic Stenosis

Abstract

Objective-Aortic stenosis (AS) shares risk factors with atherosclerotic vascular disease. Carotid intima-media thickness (IMT) and plaque may reflect the cumulative damage from exposure to different atherosclerotic risk factors. We examined the relationship of carotid IMT and plaque with incident AS in a prospective population-based study. Approach and Results-A random sample of participants (age, 45-68 years) in the population-based Malmö Diet and Cancer Study underwent B-mode ultrasound with measurements of IMT and the presence of plaque in the common carotid artery (n=5079). Potential risk factors for incident AS were studied in age-and sex-adjusted and expanded multivariable-adjusted Cox regression models. A total of 69 (1.4%) participants developed AS during up to 20 years of follow-up. Significant risk factors for AS in age-and sex-adjusted analyses were (P<0.05) body mass index, low-density lipoprotein cholesterol, hypertension, diabetes mellitus, smoking, C-reactive protein, plaque, and IMT. In contrast, highdensity lipoprotein cholesterol, triglycerides, height, and leukocyte count were not significantly associated with AS (P>0.05). After adjustments, IMT, plaque, age, smoking, C-reactive protein, low-density lipoprotein cholesterol, and diabetes mellitus remained significantly associated with incident AS. IMT was no longer significantly associated with AS after adjustments for plaque and systolic blood pressure, but plaque remained significantly associated with incident AS. ultrasound and is often a manifestation of atherosclerosis. 16,17 IMT is a risk marker for stroke and acute myocardial infarction but results are conflicting as to the added value of IMT to other established risk factors. [18][19][20][21][22][23][24][25] It has been postulated that common carotid artery IMT might also be a surrogate marker of coronary artery disease. 26 An association between IMT and aortic valve sclerosis has been established previously, 27 but it remains unclear whether the association applies to incident AS. Conclusions-TraditionalOur aim was to test the association of conventional cardiovascular risk factors, carotid IMT measures, and the presence of carotid plaque with incident AS. To our knowledge, no prospective population-based studies have examined the relationship between vascular ultrasound measurements and AS. Materials and MethodsMaterial and Methods are available in the online-only Supplement. Results Baseline CharacteristicsDuring a follow-up time of up to 20 years (mean, 16.5 years), 69 (1.4%) of the 5079 participants in the IMT samples were diagnosed with incident AS. The baseline characteristics across quartiles of IMT are shown in Table 1 Age-and Sex-Adjusted AnalysesWe observed a significant association between IMT in the common carotid artery and incident AS (hazard ratio [HR], 1.46 per 1-SD increment; P<0.01) as shown in Table 2. BMI, lowdensity lipoprotein cholesterol, CRP, diabetes mellitus, smoking, and hypertension were also associated with incident AS (P<0.05). In contrast, no significa...

Type 1 and type 2 diabetes mellitus and incidence of seven cardiovascular diseases

“…That study did not adjust for BMI, which was a strong confounder of the association between T2DM and aortic valve stenosis in our study, and a risk factor for aortic valve stenosis [17]. In two smaller prospective studies, DM was associated with an approximately 3-fold increased risk of aortic valve stenosis in a cohort of 5079 Swedish adults (including 69 cases in the whole cohort) [18] but was not associated with risk of aortic valve stenosis in a cohort of 3243 Norwegian adults, possibly because of lack of power with only 6 cases among DM patients [19]. None of the above mentioned reports specified the type of DM.…”

Temporal Trends in the Incidence and Prognosis of Aortic Stenosis

“…14 Because AS shares risk factors with AMI and HF, 4,[15][16][17][18] possible benefits from the widespread use of several cardiovascular pharmacotherapies and lifestyle improvements may also extend to AS. However, large studies investigating the temporal trends of incidence and mortality of AS in the population are lacking.…”

“…Further support for this concept comes from observations that age-related valve degeneration is characterized by inflammation and foam cell deposition in the valve tissues and angiotensin II activity, processes that are similar to atherosclerosis and that are associated with atherosclerotic disease in other vascular territories. [15][16][17]31,32 Risk factors for AS are similar to risk factors for coronary artery disease, stroke, and peripheral vascular disease and include high low-density lipoprotein cholesterol, smoking, and diabetes mellitus. [15][16][17] Recent genetic and experimental studies provide additional evidence that the disease might be preventable with lipid-modifying medications, angiotensin receptor blockers, and ACE inhibitors.…”

Genome-wide association studies of late-onset cardiovascular disease

“…[124] (Table 1) This finding has subsequently been confirmed in independent Canadian and Danish cohorts[125, 126] and reinforces the hypothesis that the process of valvular age-related degeneration shares key pathophysiologic features with that observed in atherosclerotic vessels. [127–129] In a second analysis of the same cohorts, it was further shown that a polygenic score comprised of alleles associated with increased LDL cholesterol also conferred increased risk of aortic valve calcium and stenosis, providing further support for a role of blood lipids beyond lipoprotein(a) in the development of calcific aortic valve disease. [130]…”