Nketi I. Forbang

Ankle-brachial index, toe-brachial index, and cardiovascular mortality in persons with and without diabetes mellitus

BACKGROUND The prognostic utility of the ankle-brachial index (ABI) may be hampered in persons with diabetes due to peripheral arterial stiffening in the ankles. Stiffening of toe arteries occurs infrequently in diabetes. We aimed to determine the nature of the relationship of the toe-brachial index (TBI) and ABI with cardiovascular disease (CVD) mortality and to determine whether the associations are modified in individuals with diabetes. METHODS Individuals with clinically suspected atherosclerotic peripheral arterial disease who underwent ABI and TBI measurements in a vascular laboratory were monitored longitudinally for CVD mortality. RESULTS Among 469 participants (89% men), the mean age was 68 ± 9 years, and 36% had diabetes. The mean ABI was 0.83 ± 0.28 and the mean TBI was 0.60 ± 0.24. During median 7.0 years of follow-up, there were 158 CVD deaths. The association of the ABI categories with CVD deaths differed in diabetic vs nondiabetic participants (P = .002 for interaction). In contrast, the association of the TBI categories with CVD deaths was similar, irrespective of diabetes status (P = .17 for interaction). Among diabetic patients, a U-shaped relationship was observed between ABI categories and CVD death: those with low (<0.90) and high (>1.30) ABIs were both at higher risk than those with normal ABIs (range, 0.90-1.30). In nondiabetic patients, association of ABI categories with CVD death was linear, such that those with an ABI >1.30 were at the lowest risk, whereas those with an ABI <0.90 were at higher risk. In contrast, the association of TBI categories with CVD death was linear irrespective of diabetes status. High TBI categories consistently predicted low risk, whereas risk was higher with progressively lower TBI categories. CONCLUSIONS Among diabetic individuals with clinically suspected peripheral arterial disease, those with low and high ABIs are both at higher risk of CVD death. In contrast, a linear relationship was observed between TBI categories and CVD death irrespective of diabetes status. These findings suggest that stiffened ankle arteries may limit the predictive value of the ABI in individuals with diabetes, a limitation that may be overcome by measurement of the TBI.

Sex and ethnic differences in the associations between lipoprotein(a) and peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis

OBJECTIVE Higher lipoprotein(a) [Lp(a)] has been linked with peripheral arterial disease (PAD). Also, elevated Lp(a) serum levels have been observed in women and African Americans (AAs). It remains uncertain if sex and ethnicity modify the association between Lp(a) and PAD. METHODS Lp(a) mass concentration was measured with a latex-enhanced turbidimetric immunoassay, from blood collected at baseline clinic visits after a 12-hour fast, in a multiethnic cohort. Also at baseline, the ankle-brachial index was measured. PAD was defined as an ankle-brachial index <1.0. Multivariable logistic regression was used to determine sex and ethnic differences in associations of log-transformed Lp(a) and the presence of PAD. RESULTS In 4618 participants, the mean age was 62 ± 10 years; Lp(a) mean was 30 ± 32 mg/dL and median (interquartile range) was 18 (8-40 mg/dL); 48% were male; 36% were European American, 29% were AA, 23% were Hispanic American (HA), and 12% were Chinese American; and 11% had PAD. Across all ethnic groups, serum Lp(a) was higher among women compared with men and highest among AAs compared with other ethnicities. After adjustments for traditional cardiovascular disease risk factors (age, sex, ethnicity, hypertension, diabetes, smoking, total cholesterol, and high-density lipoprotein cholesterol) as well as interleukin-6, fibrinogen, D-dimer, and homocysteine levels, one log unit increase in Lp(a) was associated with greater odds for PAD (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.01-1.25). In fully adjusted models, significant gender(∗)ln[Lp(a)] and ethnicity(∗)ln[Lp(a)] interactions were observed (P = .08 for both). The association between higher Lp(a) and PAD was strongest in HA men (OR, 1.73; 95% CI, 1.07-2.80) and HA women (OR, 1.49; 95% CI, 1.07-2.08). Nonsignificant associations were observed for European American, AA, and Chinese American men and women. CONCLUSIONS We observed a significant and independent association between elevated Lp(a) and PAD only among HA women and men, despite higher serum Lp(a) levels among AAs. Future studies are needed to determine the role that lowering of Lp(a) may have on the burden of PAD in HAs.

In vivo breath-hold 1H MRS simultaneous estimation of liver proton density fat fraction, and T1 and T2 of water and fat, with a multi-TR, multi-TE sequence

To examine the intra‐examination repeatability of proton density fat fraction (PDFF) and T1 and T2 of liver water and fat as estimated by a novel multi‐repetition time (TR)‐echo time (TE) 1H magnetic resonance spectroscopy (MRS)‐stimulated echo acquisition mode (STEAM) sequence that acquires 32 spectra for a range of TRs and TEs in single breath‐hold.

Relationship Between 24-Hour Ambulatory Blood Pressure and Cognitive Function in Community-Living Older Adults: The UCSD Ambulatory Blood Pressure Study

BACKGROUND Twenty-four-hour ambulatory blood pressure (BP) patterns have been associated with diminished cognitive function in hypertensive and very elderly populations. The relationship between ambulatory BP patterns and cognitive function in community-living older adults is unknown. METHODS We conducted a cross-sectional study in which 24-hour ambulatory BP, in-clinic BP, and cognitive function measures were obtained from 319 community-living older adults. RESULTS The mean age was 72 years, 66% were female, and 13% were African-American. We performed linear regression with performance on the Montreal Cognitive Assessment (MoCA) as the primary outcome and 24-hour BP patterns as the independent variable, adjusting for age, sex, race/ethnicity, education, and comorbidities. Greater nighttime systolic dipping (P = 0.046) and higher 24-hour diastolic BP (DBP; P = 0.015) were both significantly associated with better cognitive function, whereas 24-hour systolic BP (SBP), average real variability, and ambulatory arterial stiffness were not. CONCLUSIONS Higher 24-hour DBP and greater nighttime systolic dipping were significantly associated with improved cognitive function. Future studies should examine whether low 24-hour DBP and lack of nighttime systolic dipping predict future cognitive impairment.

Associations of diabetes mellitus and other cardiovascular disease risk factors with decline in the ankle–brachial index:

We compared the associations of diabetes mellitus (DM) and other cardiovascular disease (CVD) risk factors with decline in the ankle–brachial index (ABI) over 4 years in participants with and without peripheral artery disease (PAD). A total of 566 participants, 300 with PAD, were followed prospectively for 4 years. Mean (SD) baseline ABI values were 0.70 (0.13) for participants with both PAD and DM, 0.67 (0.14) for participants with only PAD, 1.10 (0.13) for participants with only DM, and 1.10 (0.10) for participants with neither PAD nor DM. After adjusting for age, sex, and baseline ABI, the corresponding ABI change from baseline to 4-year follow-up were −0.02, –0.04, +0.05, and +0.05, respectively. Compared to participants with neither PAD nor DM, participants with only PAD showed significantly more ABI decline (p <0.01), while the decline in participants with both PAD and DM was borderline non-significant (p = 0.06). After adjustments for baseline ABI, age, sex, African American ethnicity, and other CVD risk factors, independent factors associated with ABI decline in participants with PAD in the lower ABI leg were older age and elevated D-dimer. DM was not related to ABI decline. Despite being an important risk factor for PAD, DM was not independently associated with ABI decline. This could reflect the effect of DM promoting both PAD and lower-extremity arterial stiffness, resulting in a small decline in the ABI over time. In conclusion, ABI change over time in persons with diabetes may not accurately reflect underlying atherosclerosis.

Associations of cardiovascular disease risk factors and calcified atherosclerosis with aortoiliac bifurcation position: the MultiEthnic Study of Atherosclerosis.

We investigated associations of cardiovascular disease (CVD) risk factors and calcified atherosclerosis with aortoiliac bifurcation position. The bifurcation position was determined by measuring the distance from the aortoiliac bifurcation to the L5-S1 disk space (or aortoiliac bifurcation distance [AIBD]), using computed tomography scans. The 1711 study participants (51% male) had a mean age of 62 ± 10 years and a mean AIBD of 26 ± 15 mm. In multivariable linear regression, older age, male gender, smoking, hypertension, larger aortic diameter, and smaller lumbar height were each independently associated with a smaller AIBD (more caudal bifurcation position). In contrast, diabetes, elevated triglycerides, and increased pulse pressure were independently associated with a larger AIBD (more cephalad bifurcation position). These findings suggest that age-related bifurcation descent is associated with CVD markers for aortic disease. Future studies should assess whether the bifurcation position is an independent prognosticator for CVD.

The evolving view of coronary artery calcium and cardiovascular disease risk

Calcification of the coronary artery is a complex pathophysiologic process that is intimately associated with atherosclerosis. Extensive investigation has demonstrated the value of identifying and quantifying coronary artery calcium (CAC) in atherosclerotic cardiovascular disease (CVD) prognostication. However, over the last several years, an increasing body of evidence has suggested that CAC has underappreciated aspects that modulate, and at times attenuate, future CVD risk. The most commonly used measure of CAC, the Agatston unit, effectively models both higher density and higher area of CAC as risk factors for future CVD events. Recent findings from the Multi‐Ethnic Study of Atherosclerosis (MESA) have challenged this assumption, demonstrating that higher density of CAC is protective for coronary heart disease and CVD events. Statins may be associated with an increase in CAC, an unexpected finding given their clear benefits in the prevention and treatment of CVD. Studies utilizing intracoronary ultrasound and coronary computed tomography angiography have demonstrated that calcified atherosclerotic plaque—as compared with noncalcified or sparsely calcified plaque—is associated with fewer CVD events. These studies lend support to the often‐asserted (but as yet unvalidated) view that calcification may play a role in plaque stabilization. Furthermore, vascular calcification, though a surrogate for atherosclerotic plaque burden, may also possess identifiable aspects that can refine CVD risk assessment.

Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk: MESA (Multi-Ethnic Study of Atherosclerosis).

Background—Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard. Methods and Results—Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08–1.33; P<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04–1.59; P=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05–1.36; P<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events. Conclusions—The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries.

Association of cardiovascular disease risk factors with coronary artery calcium volume versus density

Objectives Recently, the density score of coronary artery calcium (CAC) has been shown to be associated with a lower risk of cardiovascular disease (CVD) events at any level of CAC volume. Whether risk factors for CAC volume and CAC density are similar or distinct is unknown. We sought to evaluate the associations of CVD risk factors with CAC volume and CAC density scores. Methods Baseline measurements from 6814 participants free of clinical CVD were collected for the Multi-Ethnic Study of Atherosclerosis. Participants with detectable CAC (n=3398) were evaluated for this study. Multivariable linear regression models were used to evaluate independent associations of CVD risk factors with CAC volume and CAC density scores. Results Whereas most CVD risk factors were associated with higher CAC volume scores, many risk factors were associated with lower CAC density scores. For example, diabetes was associated with a higher natural logarithm (ln) transformed CAC volume score (standardised β=0.44 (95% CI 0.31 to 0.58) ln-units) but a lower CAC density score (β=−0.07 (−0.12 to −0.02) density units). Chinese, African-American and Hispanic race/ethnicity were each associated with lower ln CAC volume scores (β=−0.62 (−0.83to −0.41), −0.52 (−0.64 to −0.39) and −0.40 (−0.55 to −0.26) ln-units, respectively) and higher CAC density scores (β= 0.41 (0.34 to 0.47), 0.18 (0.12 to 0.23) and 0.21 (0.15 to 0.26) density units, respectively) relative to non-Hispanic White. Conclusions In a cohort free of clinical CVD, CVD risk factors are differentially associated with CAC volume and density scores, with many CVD risk factors inversely associated with the CAC density score after controlling for the CAC volume score. These findings suggest complex associations between CVD risk factors and these components of CAC.

Density of calcium in the ascending thoracic aorta and risk of incident cardiovascular disease events

BACKGROUND AND AIMS The volume and density of coronary artery calcium (CAC) both independently predict cardiovascular disease (CVD) beyond standard risk factors, with CAC density inversely associated with incident CVD after accounting for CAC volume. We tested the hypothesis that ascending thoracic aorta calcium (ATAC) volume and density predict incident CVD events independently of CAC. METHODS The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of participants without clinical CVD at baseline. ATAC and CAC were measured from baseline cardiac computed tomography (CT). Cox regression models were used to estimate the associations of ATAC volume and density with incident coronary heart disease (CHD) events and CVD events, after adjustment for standard CVD risk factors and CAC volume and density. RESULTS Among 6811 participants, 234 (3.4%) had prevalent ATAC and 3395 (49.8%) had prevalent CAC. Over 10.3 years, 355 CHD and 562 CVD events occurred. One-standard deviation higher ATAC density was associated with a lower risk of CHD (HR 0.48 [95% CI 0.29-0.79], p<0.01) and CVD (HR 0.56 [0.37-0.84], p<0.01) after full adjustment. ATAC volume was not associated with outcomes after full adjustment. CONCLUSIONS ATAC was uncommon in a cohort free of clinical CVD at baseline. However, ATAC density was inversely associated with incident CHD and CVD after adjustment for CVD risk factors and CAC volume and density.