Prevalence and Correlates of Intracranial Atherosclerotic Disease Among Community-Dwelling Older Adults of Amerindian Ancestry. The Three Villages Study.

BACKGROUND: Knowledge on the prevalence and correlates of intracranial atherosclerotic disease (ICAD) is limited. We aimed to assess prevalence, clinical and neuroimaging correlates of ICAD in a cohort of older adults of Amerindian ancestry. METHODS: The study included 581 community-dwellers aged ≥60 years (mean age 71 ± 8.4 years; 57% women) living in rural Ecuadorian villages. ICAD was identified by means of CT determinations of carotid siphon calcifications (CSC) or MRA findings of significant stenosis of intracranial arteries. Fully-adjusted logistic regression models were fitted with biomarkers of ICAD as the dependent variables. RESULTS: A total of 205 (35%) of 581 participants had ICAD, including 185 with high calcium content in the carotid siphons and 40 with significant stenosis of at least one intracranial artery (20 subjects had both biomarkers). Increasing age, high fasting blood glucose, >10 enlarged basal ganglia-perivascular spaces and non-lacunar strokes were associated with high calcium content in the carotid siphons. In contrast, male gender, moderate-to-severe white matter hyperintensities, lacunar and non-lacunar strokes were associated with significant stenosis of intracranial arteries. Stroke was more common among subjects with any biomarker of ICAD than in those with no biomarkers (29% versus 9%, p < 0.001). Significant stenosis of intracranial arteries was more often associated with stroke than high calcium content in the carotid siphons, suggesting that CSC are more likely an ICAD biomarker than causally related to stroke. CONCLUSIONS: ICAD prevalence in Amerindians is high, and is significantly associated with stroke. CSC and significant stenosis of intracranial arteries may represent different phenotypes of ICAD.

Distribution of Cervicocephalic Atherosclerotic Lesions and Their Correlation with Cardiovascular Risk Factors in a Population of Amerindians. The Atahualpa Project.

BACKGROUND: No information is available on the distribution of cervicocephalic atherosclerosis in Amerindians. We aimed to assess the distribution of these lesions and their correlation with cardiovascular risk factors in Amerindians living in rural Ecuador. METHODS: Atahualpa residents aged ≥40years underwent head CT for assessment of carotid siphon calcifications (CSC) and sonographic examination for measurement of the carotid intima media thickness (cIMT). CSC were used as a surrogate of intracranial atherosclerosis and the cIMT as a surrogate of extracranial atherosclerosis. Linear regression and multinomial logistic regression models were fitted to assess the association between cIMT and CSC, and to evaluate differences in risk factors across individuals with atherosclerosis involving both arterial beds when compared with those with extra- or intracranial atherosclerosis alone, or no atherosclerosis. RESULTS: Of 590 participants, 145 had high calcium content in the carotid siphons and 87 had a cIMT >1mm (25% versus 15%, P < .001). Thirty-eight (7%) individuals had atherosclerosis at both vascular beds, 107 (18%) had intracranial atherosclerosis, and 49 (8%) had extracranial atherosclerosis alone. The cIMT and CSC were independently associated (P = .008). When compared with participants without atherosclerosis, those with atherosclerosis at both vascular beds were older, more often male, hypertensive and diabetic. Subjects with intracranial atherosclerosis alone were older, and those with extracranial atherosclerosis alone reported less physical activity than those without atherosclerosis. CONCLUSION: Intracranial atherosclerosis is more common than extracranial atherosclerosis in Amerindians. Traditional risk factors only explain a minority of cases of cervicocephalic atherosclerosis in this population.

Implications of coronary artery calcium testing on risk stratification for lipid-lowering therapy according to the 2016 European Society of Cardiology recommendations: The MESA study.

AIMS: The European Society of Cardiology (ESC) guideline on cardiovascular risk assessment considers coronary artery calcium a class B indication for risk assessment. We evaluated the degree to which coronary artery calcium can change the recommendation for individuals based on a change in estimated risk. METHODS AND RESULTS: We stratified 5602 MESA participants according to the ESC recommendation as: no lipid-lowering treatment recommended ( N = 2228), consider lipid-lowering treatment if uncontrolled ( N = 1686), or lipid-lowering treatment recommended ( N = 1688). We evaluated the ability of coronary artery calcium to reclassify cardiovascular risk. Among the selected sample, 54% had coronary artery calcium of zero, 25% had coronary artery calcium of 1-100 and 21% had coronary artery calcium greater than 100. In the lipid-lowering treatment recommended group 31% had coronary artery calcium of zero, while in the lipid-lowering treatment if uncontrolled group about 50% had coronary artery calcium of zero. The cardiovascular mortality rate was 1.7%/10 years in the lipid-lowering treatment if uncontrolled, and 7.0%/10 years in the lipid-lowering treatment recommended group. The absence of coronary artery calcium was associated with 1.4%/10 years in the lipid-lowering treatment if uncontrolled group and 3.0%/10 years in the lipid-lowering treatment recommended group. Compared with coronary artery calcium of zero, any coronary artery calcium was associated with significantly higher cardiovascular mortality in the lipid-lowering treatment recommended group (9.0%/10 years), whereas only coronary artery calcium greater than 100 was significantly associated with a higher cardiovascular mortality in the lipid-lowering treatment if uncontrolled group (3.2%/10 years). CONCLUSION: The absence of coronary artery calcium is associated with a low incidence of cardiovascular mortality or coronary heart disease events even in individuals in whom lipid-lowering therapy is recommended. A significant proportion of individuals deemed to be candidates for lipid-lowering therapy might be reclassified to a lower risk group with the use of coronary artery calcium.

The prevalence and correlates of subclinical atherosclerosis among adults with low-density lipoprotein cholesterol <70 mg/dL: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND AND AIMS: The prevalence and correlates of subclinical atherosclerosis when low-density lipoprotein cholesterol (LDL-C) levels are low remain unclear. Therefore, we examined the association of cardiovascular risk factors and subclinical atherosclerosis among individuals with untreated LDL-C <70 mg/dL. METHODS: We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohorts. To optimize accuracy, LDL-C was calculated by the validated Martin/Hopkins equation that uses an adjustable factor for the ratio of triglycerides to very low-density lipoprotein cholesterol. We defined subclinical atherosclerosis as a coronary artery calcium (CAC) score >0 in the combined cohort or common carotid intima media thickness (cIMT) in the 4th quartile, using cohort-specific cIMT distributions at baseline. Logistic regression models examined the cross-sectional associations of cardiovascular risk factors and subclinical atherosclerosis. RESULTS: Among 9411 participants not on lipid lowering therapy, 263 (3%) had LDL-C <70 mg/dL (MESA: 206, ELSA: 57). Mean age in this population was 58 (SD 12) years, with 43% men, and 41% Black. The prevalence of CAC >0 in those with untreated LDL-C<70 mg/dL was 30%, and 18% were in 4th quartile of cIMT. In demographically adjusted models, only ever smoking was significantly associated with both CAC and cIMT. Similar results were obtained in risk factor-adjusted models (smoking: OR, 2.29; 95% CI, 1.10-4.80 and OR, 3.44; 95% CI, 1.41-8.37 for CAC and cIMT, respectively). CONCLUSIONS: Among middle-aged to older individuals with untreated LDL-C <70 mg/dL, subclinical atherosclerosis remains moderately common and is associated with cigarette smoking.

Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in african ancestry men.

BACKGROUND AND AIMS: There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men. METHODS: Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height. RESULTS: All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC. CONCLUSIONS: Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body.

Age, Gender, and Race-Based Coronary Artery Calcium Score Percentiles in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Coronary artery calcium (CAC) has been demonstrated to independently predict the risk of cardiovascular events and all-cause mortality, especially among White populations. Although the population distribution of CAC has been determined for several White populations, the distribution in ethnically admixed groups has not been well established. HYPOTHESIS: The CAC distribution, stratified for age, gender and race, is similar to the previously described distribution in the MESA study. METHODS: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a prospective cohort study designed to investigate subclinical cardiovascular disease in 6 different centers of Brazil. Similar to previous studies, individuals with self-reported coronary or cerebrovascular disease and those treated for diabetes mellitus were excluded from analysis. RESULTS: Percentiles of CAC distribution were estimated with nonparametric techniques. The analysis included 3616 individuals (54% female; mean age, 50 years). As expected, CAC prevalence and burden were steadily higher with increasing age, as well as increased in men and in White individuals. Our results revealed that for a given CAC score, the ELSA-derived CAC percentile would be lower in men compared with the Multi-Ethnic Study of Atherosclerosis (MESA) and would be higher in women compared with MESA. CONCLUSIONS: In our sample of the Brazilian population, we observed significant differences in CAC by sex, age, and race. Adjusted for age and sex, low-risk individuals from the Brazilian population present with significantly lower CAC prevalence and burden compared with other low-risk individuals from other worldwide populations. Using US-derived percentiles in Brazilian individuals may lead to overestimating relative CAC burden in men and underestimating relative CAC burden in women.

Inflammatory/hemostatic biomarkers and coronary artery calcification in midlife women of African-American and White race/ethnicity: the Study of Women's Health Across the Nation (SWAN) heart study.

OBJECTIVE: Inflammatory/hemostatic biomarkers are associated with coronary heart disease events, but relationships in asymptomatic midlife women are uncertain. We evaluated separately whether high-sensitivity C-reactive protein (hsCRP), fibrinogen, plasminogen-activator inhibitor 1, tissue plasminogen activator antigen, and circulating factor VII (factor VIIc) were associated with coronary artery calcification (CAC) in healthy midlife women. METHODS: A cross-sectional study was performed of participants from the Study of Women's Health Across the Nation. Logistic and Tobit regression was used to assess associations between log-transformed biomarkers, and CAC presence (CAC > 0) and extent. Effect modification by race/ethnicity was evaluated. RESULTS: The study included 372 women (mean age 51.3 y; 35.2% African-American). All biomarkers were positively associated with CAC presence and extent (P < 0.001 for all), adjusting for Framingham risk score, site, race/ethnicity, menopause status, income, and education. Additional adjustment for body mass index explained all associations except for factor VIIc, which remained associated with CAC extent only (P = 0.02). Final adjustment for insulin resistance, family history of cardiovascular disease, and cardiovascular medication use produced similar results. Associations between hsCRP, and CAC presence and extent were modified by race/ethnicity (P < 0.05). Log(hsCRP) was positively associated with CAC presence (odds ratio 3.25; 95% CI, 1.53-6.90; P = 0.002; per 1 log unit increase) and CAC extent (ß = 19.66; SE = 7.67; P = 0.01; per 1 log unit increase) in African-Americans only. CONCLUSIONS: Inflammatory/hemostatic biomarkers were associated with CAC through obesity, except for factor VIIc. Among African-American women only, hsCRP was independently associated with CAC, suggesting that hsCRP may have a role in coronary heart disease prevention in African-American midlife women.

Association of circulating sclerostin with vascular calcification in Afro-Caribbean men.

OBJECTIVE: Sclerostin, a Wingless (Wnt) pathway antagonist, is an established regulator of bone mineralization in humans but its potential importance in the regulation of vascular calcification is less clear. Therefore, our objective was to assess the relationship of serum sclerostin levels with coronary and aortic artery calcification (CAC and AAC, respectively) in Afro-Caribbean men on the island of Tobago. METHODS: Serum sclerostin levels and computed tomography of CAC and AAC were measured in 191 men (age mean(SD): 62.9(8.0)years) recruited without regard to health status. Multivariable logistic regression models were used to assess the cross-sectional association of sclerostin with prevalent arterial calcification. RESULTS: Mean(SD) sclerostin was 45.2 pmol/L (15.6 pmol/L). After adjusting for risk factors including age, physical and lifestyle characteristics, comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level was associated with a 1.61-times (95%CI 1.02-2.53) greater odds of having CAC. Sclerostin was not associated with AAC in any model. CONCLUSIONS: This is the first study to show that, among Afro-Caribbean men, greater serum sclerostin concentrations were associated with prevalence and extent of CAC. Further studies are needed to better define the role of the Wnt signaling pathway in arterial calcification in humans.

Association of volumetric bone mineral density with abdominal aortic calcification in African ancestry men.

SUMMARY: We tested for association between cortical and trabecular volumetric bone mineral density (vBMD) with abdominal aortic calcification (AAC) prevalence in 278 Afro-Caribbean men. AAC was present in 68.3 % of the men. Greater cortical, but not trabecular, vBMD was associated with significantly decreased odds of AAC independent of traditional risk factors. INTRODUCTION: The aim of this study is to assess the prevalence and correlates of AAC in a sample of 278 Afro-Caribbean men (mean age 56) and to test for a largely unexplored association between cortical and trabecular vBMD with AAC prevalence. METHODS: Men were recruited consecutively as part of an ongoing prospective cohort study of body composition in men aged 40+. For this analysis, AAC was assessed by computed tomography of the abdomen from L3 to S1. Aortic calcium was scored using the Agatston method, and prevalence was defined as a score ≥10 to rule out false positives. Men also had BMD assessed using peripheral quantitative computed tomography at 4 % (trabecular vBMD) and 33 % (cortical vBMD) of the radius and tibia. RESULTS: Abdominal aortic calcification was present in 68.3 % of the men. Significant independent predictors of AAC prevalence were increased age, increased BMI, hypertension, and current smoking. Age was the strongest predictor, with each SD (7.8 year) increase in age conferring 2.7 times increased odds of having AAC (P < 0.0001). A one SD greater cortical, but not trabecular, vBMD was associated with a significant decreased odds of AAC prevalence independent of other traditional risk factors (OR 0.65; 95 % CI 0.45-0.92). CONCLUSIONS: Cortical vBMD is inversely associated with AAC presence. This finding suggests that there may be shared physiology between cortical bone compartment remodeling and vascular calcification.

Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

BACKGROUND: Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. METHODS: We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. FINDINGS: Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; p<0·0001) and with the number of arterial beds involved (mean age was 32 [SD 15] years for mummies with no atherosclerosis, 42 [10] years for those with atherosclerosis in one or two beds, and 44 [8] years for those with atherosclerosis in three to five beds; p<0·0001). INTERPRETATION: Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in premodern human beings raises the possibility of a more basic predisposition to the disease. FUNDING: National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Luke's Hospital Foundation of Kansas City.