Cheeling Chan

Prevalence and Progression of Subclinical Atherosclerosis in Younger Adults With Low Short-Term but High Lifetime Estimated Risk For Cardiovascular Disease The Coronary Artery Risk Development in Young Adults Study and Multi-Ethnic Study of Atherosclerosis

Background— We hypothesized that individuals with low 10-year but high lifetime cardiovascular disease risk would have a greater burden of subclinical atherosclerosis than those with low 10-year but low lifetime risk. Methods and Results— We included 2988 individuals ≤50 years of age at examination year 15 from the Coronary Artery Risk Development in Young Adults (CARDIA) study and 1076 individuals ≤50 of age at study entry from the Multi-Ethnic Study of Atherosclerosis (MESA). The 10-year risk and lifetime risk for cardiovascular disease were estimated for each participant, permitting stratification into 3 groups: low 10-year (<10%)/low lifetime (<39%) risk, low 10-year (<10%)/high lifetime risk (≥39%), and high 10-year risk (≥10%) or diagnosed diabetes mellitus. Baseline levels and change in levels of subclinical atherosclerosis (coronary artery calcium or carotid intima-media thickness) were compared across risk strata. Among participants with low 10-year risk (91% of all participants) in CARDIA, those with a high lifetime risk compared with low lifetime risk had significantly greater common (0.83 versus 0.80 mm in men; 0.79 versus 0.75 mm in women) and internal (0.85 versus 0.80 mm in men; 0.80 versus 0.76 mm in women) carotid intima-media thickness, higher coronary artery calcium prevalence (16.6% versus 9.8% in men; 7.1% versus 2.3% in women), and significantly greater incidence of coronary artery calcium progression (22.3% versus 15.4% in men; 8.7% versus 5.3% in women). Similar results were observed in MESA. Conclusions— Individuals with low 10-year but high lifetime risk have a greater subclinical disease burden and greater incidence of atherosclerotic progression compared with individuals with low 10-year and low lifetime risk, even at younger ages.

Statin Use and Leg Functioning in Patients With and Without Lower-Extremity Peripheral Arterial Disease

Background—We determined whether statin use (versus nonuse) is associated with superior lower-extremity functioning independently of cholesterol levels and other confounders in patients with and without peripheral arterial disease. Methods and Results—Participants included 392 men and women with an ankle brachial index (ABI) <0.90 and 249 with ABI 0.90 to 1.50. Functional outcomes included 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ABI, comorbidities, education level, medical insurance status, cholesterol, and other confounders, participants taking statins had better 6-minute walk performance (1276 versus 1218 feet, P =0.045), faster walking velocity (0.93 versus 0.89 m/s, P =0.006), and a higher summary performance score (10.2 versus 9.4, P <0.001) than participants not taking statins. Positive associations were attenuated slightly after additional adjustment for C-reactive protein level but remained statistically significant for walking velocity and the summary performance score. We did not find significant associations between lower-extremity functioning and aspirin, ACE inhibitors, vasodilators, or &bgr;-blockers. Conclusions—Statin use is associated with superior leg functioning compared with no statin use, independent of cholesterol levels and other potential confounders. These data suggest that non–cholesterol-lowering properties of statins may favorably influence functioning in persons with and without peripheral arterial disease.

Association of Acculturation Levels and Prevalence of Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)

OBJECTIVE—The prevalence of type 2 diabetes among Hispanic and Asian Americans is increasing. These groups are largely comprised of immigrants who may be undergoing behavioral and lifestyle changes associated with development of diabetes. We studied the association between acculturation and diabetes in a population sample of 708 Mexican-origin Hispanics, 547 non–Mexican-origin Hispanics, and 737 Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA). RESEARCH DESIGN AND METHODS—Diabetes was defined as fasting glucose ≥126 mg/dl and/or use of antidiabetic medications. An acculturation score was calculated for all participants using nativity, years living in the U.S., and language spoken at home. The score ranged from 0 to 5 (0 = least acculturated and 5 = most acculturated). Relative risk regression was used to estimate the association between acculturation and diabetes. RESULTS—For non–Mexican-origin Hispanics, the prevalence of diabetes was positively associated with acculturation score, after adjustment for sociodemographics. The prevalence of diabetes was significantly higher among the most acculturated versus the least acculturated non–Mexican-origin Hispanics (prevalence ratio 2.49 [95% CI 1.14−5.44]); the higher the acculturation score is, the higher the prevalence of diabetes (P for trend 0.059). This relationship between acculturation and diabetes was partly attenuated after adjustment for BMI or diet. Diabetes prevalence was not related to acculturation among Chinese or Mexican-origin Hispanics. CONCLUSIONS—Among non–Mexican-origin Hispanics in MESA, greater acculturation is associated with higher diabetes prevalence. The relation is at least partly mediated by BMI and diet. Acculturation is a factor that should be considered when predictors of diabetes in racial/ethnic groups are examined.

Relation of Levels of Hemostatic Factors and Inflammatory Markers to the Ankle Brachial Index

Associations between hemostatic and inflammatory markers relative to the ankle brachial index (ABI), an indicator of the presence and severity of peripheral arterial disease (PAD), are not fully understood. We studied relations among selected hemostatic factors, inflammatory markers, and the ankle brachial index (ABI) in patients with and without peripheral arterial disease (PAD). Participants were 370 men and women with ABI <0.90 and 231 patients with ABI 0.90 to 1.50 identified from noninvasive vascular laboratories and general medicine practice. Blood factors were D-dimer, prothrombin 1.2, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1), and inflammatory markers (high-sensitivity C-reactive protein [CRP], fibrinogen, and serum amyloid A [SAA]). Among patients without a history of cardiac or cerebrovascular disease, the ABI was significantly inversely associated with log D-dimer (p <0.001), log prothrombin 1.2 (p = 0.001), log CRP (p <0.001), and log fibrinogen (p = 0.005) in unadjusted analyses. In multivariable regression analyses adjusting for all blood factors as well as potential confounders, D-dimer was associated independently with ABI in participants with a history of cardiac or cerebrovascular disease (p = 0.003) and in participants without a history of cardiac or cerebrovascular disease (p = 0.017). In these analyses, CRP was associated independently with ABI among participants with a history of cardiac or cerebrovascular disease (p = 0.026). CRP was not associated independently with ABI in participants without a history of cardiac or cerebrovascular disease. We conclude that D-dimer levels may be more sensitive than other blood markers for measuring the extent of atherosclerosis in lower extremity arteries.

Sex differences in peripheral arterial disease: Leg symptoms and physical functioning

OBJECTIVES:LTo compare lower extremity functioning and leg symptoms between women and men with peripheral arterial disease (PAD).

D-Dimer, Inflammatory Markers, and Lower Extremity Functioning in Patients With and Without Peripheral Arterial Disease

Background—We determined whether higher levels of D-dimer, C-reactive protein (CRP), fibrinogen, and serum amyloid A are associated independently with functional impairment in patients with and without peripheral arterial disease (PAD). Methods and Results—Participants were 370 men and women with PAD (ankle brachial index <0.90) and 231 without PAD. Functional outcomes were 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ankle brachial index, comorbidities, and other potential mediators and confounders, D-dimer levels were associated independently and inversely with performance on all 3 functional measures in the entire cohort and among patients with and without PAD, respectively. Adjusting for known and potential confounders, CRP levels were associated independently with 6-minute walk distance and the summary performance score among participants with PAD. No significant associations were observed between CRP and the functional measures among participants without PAD. Fibrinogen and SAA levels were not associated independently with the functional measures. Conclusions—Higher D-dimer levels are associated with poorer functioning among individuals with and without PAD. Higher CRP levels were associated with poorer 6-minute walk performance and a lower summary performance score among participants with PAD but not among those without PAD. Additional study is needed to determine whether D-dimer and CRP are involved in the pathophysiology of functional impairment or whether they are simply sensitive markers of the extent of systemic atherosclerosis.

Depressive symptoms and lower extremity functioning in men and women with peripheral arterial disease.

AbstractOBJECTIVE: Factors associated with impaired functioning in patients with lower extremity peripheral arterial disease (PAD) are not fully understood. The purpose of this study was to determine the relationship between depressive symptoms and objective measures of lower extremity functioning in persons with PAD. DESIGN: Cross-sectional. PATIENTS/PARTICIPANTS: Four hundred twenty-three men and women with PAD identified from 3 Chicago area medical centers. MEASUREMENTS AND MAIN RESULTS: PAD was defined as ankle brachial index (ABI) <0.90. The Geriatric Depression Scale short form (GDS-S) (0–15 scale, 15 = worst) was completed by all participants. A clinically significant number of depressive symptoms was defined as a GDS-S score ≥6. Six-minute walk distance and usual-and fast-pace walking velocity were determined for all participants. A GDS-S score ≥6 was present in 21.7% of participants with PAD. Adjusting for age, increasing numbers of depressive symptoms were associated with an increasing prevalence of leg pain on exertion and rest (P=.004). Adjusting for age, sex, race, ABI, number of comorbidities, current smoking, and antidepressant medications, increasing numbers of depressive symptoms were associated with shorter 6-minute walk distance (P<.001), slower usual-pace walking velocity (P=.005), and slower fast-pace walking velocity (P=.005). These relationships were attenuated slightly after additional adjustment for presence versus absence of leg pain on exertion and rest and severity of exertional leg symptoms. CONCLUSIONS: Among men and women with PAD, the prevalence of a clinically significant number of depressive symptoms is high. Greater numbers of depressive symptoms are associated with greater impairment in lower extremity functioning. Further study is needed to determine whether identifying and treating depressive symptoms in PAD is associated with improved lower extremity functioning.

Elevated Fibrinogen Levels and Subsequent Subclinical Atherosclerosis: The CARDIA Study

OBJECTIVE To determine whether elevated levels of hemostatic factors are associated with the subsequent development of subclinical cardiovascular disease. METHODS Fibrinogen, factors VII (FVII) and VIII (FVIII), and von Willebrand factor (vWF) were measured in 1396 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Coronary artery calcification (CAC) and carotid intimal/medial thickness (CIMT) were determined 13 years later. The adjusted prevalence of CAC and mean CIMT across the quartiles of each hemostatic factor was computed for the total sample and for each race and gender group. RESULTS The age-, race-, and gender-adjusted prevalences of CAC with increasing quartiles of fibrinogen were 14.4%, 15.2%, 20.0%, and 29.1% (p<0.001 for trend). This trend persisted after further adjustment for body mass index (BMI), smoking, educational level, center, systolic blood pressure (BP), diabetes, antihypertensive medication use, total and high-density lipoprotein (HDL) cholesterol, and CRP. A similar trend was observed for CIMT (age-, race- and gender-adjusted, p<0.001; multivariable-adjusted, p=0.014). Further analyses of race and gender subgroups showed that increasing quartiles of fibrinogen were associated with CAC and CIMT in all subgroups except black men. The prevalence of CAC was not associated with increasing quartiles of FVII, FVIII, or vWF, suggesting they may be less involved in plaque progression. CONCLUSION An elevated fibrinogen concentration in persons aged 25-37 is independently associated with subclinical cardiovascular disease in the subsequent decade.

Lower Extremity Performance Is Associated with Daily Life Physical Activity in Individuals with and without Peripheral Arterial Disease

OBJECTIVES To determine whether persons with poorer lower extremity functioning have reduced physical activity levels. DESIGN Cross-sectional. SETTING Three Chicago-area medical centers. PARTICIPANTS Two hundred twenty-five people with lower extremity peripheral arterial disease (PAD) and 121 individuals without PAD. MEASUREMENTS The summary performance score (SPS) was determined for all participants. The SPS combines data on walking velocity, time for five repeated chair rises, and standing balance. Each test is scored on a 0 to 4 scale (4 = best). Scores are summed to create the SPS (0-12 scale, 12 = best). All participants wore a vertical accelerometer for 7 days to measure physical activity. RESULTS The SPS was associated linearly with 7-day physical activity levels of participants with (P< .0001) and without PAD (P< .0001). This relationship was maintained even after restricting analyses to subsets of participants who reported that they could walk a quarter of a mile and up and down stairs without difficulty (P< .001) and were able to walk for 6-minutes without stopping (P< .001). In multiple linear regression analyses, the SPS was associated with physical activity in participants with (P< .01) and without PAD (P< .001), adjusting for age, sex, race, comorbidities, ankle brachial index, neuropathy, and leg symptoms. CONCLUSION In people with and without PAD who have impaired lower extremity performance, reduced physical activity levels may contribute to subsequent disability. Future study is needed to determine whether interventions to increase physical activity can prevent functional decline in persons with a low SPS.

Relationship of body mass index in young adulthood and health-related quality of life two decades later: the Coronary Artery Risk Development in Young Adults study

Objective:The expanding overweight and obesity epidemic notwithstanding, little is known about their long-term effect on health-related quality of life (HRQoL). The main objective of this study was to investigate whether overweight (body mass index (BMI) 25 to <30 kg m−2) and obese (BMI ⩾30 kg m−2) young adults have poorer HRQoL 20 years later.Methods:We studied 3014 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal, community-dwelling, biracial cohort from four cities. BMI was measured at baseline and 20 years later. HRQoL was assessed by the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores of the Medical Outcomes Study 12-Item Short-Form Health Survey at year 20. Higher PCS or MCS scores indicate better HRQoL.Results:Mean year 20 PCS score was 52.2 for normal weight participants at baseline, 50.3 for overweight and 46.4 for obese (P-trend <0.001). This relation persisted after adjustment for baseline demographics, general health, and physical and behavioral risk factors and after further adjustment for 20-year changes in risk factors. No association was observed for MCS scores (P-trend 0.43).Conclusion:Overweight and obesity in early adulthood are adversely associated with self-reported physical HRQoL, but not mental HRQoL 20 years later.