Intimal and medial calcification in relation to cardiovascular risk factors.

PURPOSE: To assess specific risk factors and biomarkers associated with intimal arterial calcification (IAC) and medial arterial calcification (MAC). METHODS: We conducted a cross-sectional study in patients with or at risk of vascular disease from the SMART study(n = 520) and the DCS cohort(n = 198). Non-contrast computed tomography scanning of the lower extremities was performed and calcification in the femoral and crural arteries was scored as absent, predominant IAC, predominant MAC or indistinguishable. Multinomial regression models were used to assess the associations between cardiovascular risk factors and calcification patterns. Biomarkers for inflammation, calcification and vitamin K status were measured in a subset of patients with IAC(n = 151) and MAC(n = 151). RESULTS: Femoral calcification was found in 77% of the participants, of whom 38% had IAC, 28% had MAC and 11% were scored as indistinguishable. The absolute agreement between the femoral and crural arteries was high(69%). Higher age, male sex, statin use and history of coronary artery disease were associated with higher prevalences of femoral IAC and MAC compared to absence of calcification. Smoking and low ankle-brachial-index (ABI) were associated with higher prevalence of IAC and high ABI was associated with less IAC. Compared to patients with IAC, patients with MAC more often had diabetes, have a high ABI and were less often smokers. Inactive Matrix-Gla Protein was associated with increased MAC prevalence, while osteonectin was associated with decreased risk of MAC, compared to IAC. CONCLUSIONS: When femoral calcification is present, the majority of the patients have IAC or MAC throughout the lower extremity, which have different associated risk factor profiles.

Calcification of the splenic, iliac, and breast arteries and risk of all-cause and cardiovascular mortality.

BACKGROUND AND AIMS: CVD risks associated with coronary artery calcification (CAC) and aortic calcification (AC) are well known, but less is known about other calcified arteries. We aimed to assess the associations of arterial calcification in the breast, splenic, and internal and external iliac arteries with CVD risk factors and mortality. METHODS: We conducted a case-cohort study nested in a cohort of 5196 individuals who self-referred or were referred by a health care provider for whole body computed tomography (CT), including a random subcohort (n = 395) and total and CVD mortality cases (n = 298 and n = 90), who died during a median follow-up of 9.4 years. Arterial calcification in the breast, splenic, and internal and external iliac arteries on CT was scored using a simple visual score. AC and CAC were previously measured using the Agatston technique. Logistic regression models were made to study associations of CVD risk factors with calcification in the different vascular beds. Prentice-weighted Cox proportional hazards models adjusted for CVD risk factors, and calcification in other vascular beds, were used to study associations with mortality. RESULTS: In the subcohort, the mean age was 56.6 years (SD 11.1) and 41.3% were female. The prevalence of calcification on CT, was 11.6% in the splenic, 47.9% in the internal iliac and 9.5% in the external iliac arteries, while 3.7% of women had breast artery calcification (BAC). Calcification in the splenic and iliac arteries was associated with calcification in the abdominal aorta but differentially associated with other CVD risk factors in logistic regression models. The prevalence of BAC was too low to fit these multivariable models. Calcification of the external iliac arteries was significantly associated with both all-cause and CVD mortality, but no longer significant when adjusted for CVD risk factors. Breast artery calcification was associated with both all-cause and CVD mortality independent of CVD risk factors and AAC and CAC (all-cause HR 5.67 [95% CI 1.50-21.41]). CONCLUSIONS: Risk factors associated with calcification, and the association of calcification with risk of mortality differ across vascular beds, possibly reflecting different pathophysiology.

Association of High Ankle Brachial Index With Incident Cardiovascular Disease and Mortality in a High-Risk Population.

OBJECTIVE: The objective of this present study is to determine whether high ankle brachial index (ABI) as compared with ABIs within reference limits is associated with an increased incidence of cardiovascular disease (CVD) events and all-cause mortality in a high-risk population and whether this association is the same for patients with and without diabetes mellitus or prevalent CVD. APPROACH AND RESULTS: Seven thousand five hundred and thirty-eight patients with ABI>0.9 and either prevalent CVD or a high risk for CVD were selected from the Second Manifestations of Arterial Disease (SMART) study. Three hundred and thirty-six participants (4.5%) had high ABI (≥1.4 or incompressible). Higher age, male sex, higher body mass index, and diabetes mellitus were associated with higher prevalences of high ABI; smoking and higher non-high-density lipoprotein levels were associated with lower prevalences of high ABI. Cox proportional hazards models were fitted assessing the association of high ABI (as compared with ABI 0.9-1.4) with the risk of myocardial infarction, stroke, cardiovascular death, the combined outcome of these 3, and total mortality (median follow-up 6.9 years). After multivariable adjustment, high ABI was associated with an increased risk of myocardial infarction (hazard ratio 1.83 [95% confidence interval 1.22-2.76]), but not with stroke (hazard ratio 0.86 [95% confidence interval 0.44-1.69]), cardiovascular (hazard ratio 1.14 [95% confidence interval 0.70-1.84]), or all-cause mortality (hazard ratio 0.95 [95% confidence interval 0.67-1.34]). Associations of high ABI with CVD outcomes tended to be stronger in patients with diabetes mellitus but without statistically significant interactions. CONCLUSIONS: In a high-risk population, the presence of an ABI≥1.4 was associated with an increased risk for myocardial infarction, but not with stroke, all-cause, or vascular mortality.

Breast arterial calcifications: a systematic review and meta-analysis of their determinants and their association with cardiovascular events.

OBJECTIVE: Breast arterial calcifications (BAC), regularly observed at mammography, are medial calcifications and as such an expression of arteriosclerosis. Our objective was to evaluate and summarize the available evidence on the associations of BAC with cardiovascular risk factors and cardiovascular risk. METHODS: A systematic literature review and meta-analysis were conducted. Embase and PubMed databases were searched. After critical appraisal, odds ratios were extracted from studies of moderate or good quality that examined risk factors for BAC or associations of BAC with cardiovascular disease. Random effects model meta-analyses were used to calculate pooled odds ratios and 95% confidence intervals (95%CIs). RESULTS: BAC prevalence is around 12.7% among women in breast cancer screening programs. Increasing age (pooled OR 2.98 [95%CI 2.31-3.85] for every 10 years), diabetes (pooled OR: 1.88 [95%CI 1.36-2.59]) and parity as opposed to nulliparity (pooled OR 3.43 [95%CI 2.23-5.27]) are associated with higher BAC prevalence. Smoking is associated with lower BAC prevalence (pooled OR 0.48 [95%CI 0.39-0.60]). No associations were found with hypertension, obesity or dyslipidemia. Although longitudinal studies (n = 3) were scarce, BAC appear to be associated with an increased risk of cardiovascular disease events (adjusted hazard ratios for coronary heart disease ranging from 1.32 [95%CI 1.08-1.60] to 1.44 [95%CI1.02-2.05]). CONCLUSION: BAC appear to be associated with an increased risk of cardiovascular disease events, while only being associated with some of the known cardiovascular risk factors, illustrating that medial arterial calcification might contribute to cardiovascular disease through a pathway distinct from the intimal atherosclerotic process.

The influence of informant characteristics on the reliability of family history interviews.

Family history interviews are widely used in psychiatric research, as well as in genetic and twin studies, and provide a way to collect family history information quickly and economically. To obtain a valid assessment of family history, it is important to investigate which family member will be able to provide accurate information. Previous research shows that the validity of family history reporting can be influenced by characteristics of the informant, such as age, gender and personal history of psychiatric disorder. The aim of this study was to investigate the role of a subject's position in a pedigree on the validity of data collection. Family history data on diabetes and psychiatric disorders were collected in three generations of 33 families by interviewing both an index subject (3rd generation) and his or her mother (2nd generation). Mothers were shown to report higher rates of diabetes and psychiatric disorder in the family compared to the index subjects. There was no significant difference in the disease rate reported by male and female index subject. Mothers who experienced a depressive episode indicated significantly more family members as having a psychiatric disorder than mothers who never experienced such an episode. This could be explained by the presence of informant bias, but may also result from the fact that depression is a heritable disorder and is therefore actually more prevalent in these families. Our findings suggest that family interview data should be collected by interviewing subjects who have a central position in the pedigree and can therefore provide information on his/her own generation, the previous and the next. In addition, psychiatric status of the informant should be carefully addressed.