Nutritional Avocado Intervention Improves Physical Activity Measures in Hispanic/Latino Families: A Cluster RCT.

Introduction: Nutrition and physical activity are key components for the prevention of cardiovascular disease. There remains a paucity of trial data on the effect of specific nutritional interventions on physical activity and sedentary time. One question is how a common nutrient-dense food such as avocado may impact physical activity and sedentary time in Hispanic/Latino families, a group that reports the lowest levels of physical activity. Design: This is a 6-month clustered RCT. Setting/participants: Seventy-two families (235 individuals) who identified as Hispanic/Latino were enrolled through the San Ysidro Health Center (San Diego, CA) between April 2017 and June 2018. Intervention: After a 2-week run-in period, 35 families were randomized to the intervention arm (14 avocados/family/week), and 37 families were assigned to the control arm (3 avocados/family/week). Main outcome measures: Linear mixed-effects models were used to assess changes in physical activity (MET minutes per week) between the groups during the 6-month trial. Secondary outcomes included sedentary time (minutes/week), BMI, and systolic and diastolic blood pressures. Results: An adherence goal of >80% was achieved for both arms. Total mean physical activity increased by 2,197 MET minutes per week more in the intervention group (p<0.01) than in the control group, driven by between-group differences in moderate (p<0.01) versus vigorous (p=0.06) physical activity. After accounting for longitudinal repeated measures per participant and nested family effects, total adult physical activity remained significantly higher in the intervention than in the control group (+1,163 MET minutes per week on average per participant), with a significant intervention interaction term (p<0.01). There were no significant changes in sedentary time, BMI, or blood pressure. Conclusions: Higher allocation of avocados was associated with significantly higher physical activity and no adverse changes in BMI or blood pressure, suggesting that this nutritional intervention may have beneficial pleiotropic effects.Trial registration: This study is registered at www.clinicaltrials.gov as NCT02903433.

Inter-arm systolic blood pressure difference: non-persistence and association with incident cardiovascular disease in the Multi-ethnic Study of Atherosclerosis.

We investigated inter-arm systolic blood pressure (sIAD) difference, reproducibility, and incident cardiovascular disease (CVD). We hypothesized that higher sIAD values have low prevalence and nonpersistence over years, but that CVD risk is higher starting from the time of first high absolute sIAD. In Multi-Ethnic Study of Atherosclerosis participants (n = 6725, 53% female, 45-84 years old), Doppler systolic blood pressure (SBP) measurements were made in both arms (10-minute interval) thrice over 9.5 years. Proportional hazards for CVD (coronary heart disease, heart failure, stroke, peripheral arterial disease (PAD)) over 16.4 years were tested according to time-varying absolute inter-arm difference with covariates: (1) age, gender, race, and clinic; (2) model 1 plus height, heart rate, BP, antihypertensives, BMI, smoking status, lipids, lipid lowering medication, and diabetes. High sIAD was not persistent across exams. Maximum absolute sIAD ≥ 15 mmHg was found at least once in 815 persons. Maximum absolute sIAD had a graded relationship with incident stroke or PAD: 6.2% events; model 2 hazard ratio per 10 mmHg 1.34 (95% CI, 1.15-1.56) and this risk was approximately doubled for maximum absolute sIAD ≥ 15 mmHg vs 0-4 mmHg. Total CVD risk (18.4% events) was increased only for maximum absolute sIAD ≥25 mmHg. Associations with incident CVD did not differ for higher SBP in left vs right arm. A higher maximum absolute sIAD at any exam was associated with greater risk for stroke and PAD especially for values ≥ 15 mmHg, and ≥25 mmHg for other CVD. Measuring SBP between arms may help identify individuals at risk for CVD.

Associations of Perirenal Fat Thickness with Renal and Systemic Calcified Atherosclerosis.

BACKGROUND: We investigated associations between perirenal fat thickness and atherosclerotic calcification in six different vascular beds. METHODS: Using a community-based cohort (n=3,919), perirenal fat thickness was estimated from computed tomography scans. It was classified as Q1 (the lowest quartile) to Q4 (the highest quartile) in each sex. Calcification in the carotid arteries, coronary arteries, thoracic aorta, abdominal aorta, iliac arteries, and renal arteries was evaluated. RESULTS: Perirenal fat thickness was associated with older age (P<0.01) and a higher prevalence of obesity, hypertension, and dyslipidemia (P<0.01 for all). Perirenal fat thickness was independently associated with renal arterial calcification even after adjustment for age, sex, body mass index, hypertension, dyslipidemia, smoking history, and family history of heart diseases in first-degree relatives (odds ratio [OR] per quartile of perirenal fat thickness, 1.25; 95% confidence interval [CI], 1.09 to 1.44). Compared to Q1, the odds of renal arterial calcification in Q4 was about two times higher (OR, 2.05; 95% CI, 1.29 to 3.25). After adjustment for renal arterial calcification and atherosclerotic risk factors, the only other vascular bed where perirenal fat thickness showed a significant association with calcification was the abdominal aorta (OR, 1.11; 95% CI, 1.00 to 1.23; P=0.045). CONCLUSION: Perirenal fat thickness was independently associated with vascular calcification in the renal artery and abdominal aorta.

The association between liver fat and systemic calcified atherosclerosis.

BACKGROUND: The association of nonalcoholic fatty liver disease (NAFLD) with systemic calcified atherosclerosis, other than the coronary arteries, has not been clearly elucidated. We investigated the association between NAFLD and calcification in eight different vascular beds. METHODS: In a community-based cohort with computed tomography scans for carotid artery, coronary artery, thoracic aorta, abdominal aorta, iliac artery, renal artery, celiac trunk, and superior mesenteric artery, the association between NAFLD and arterial calcification was evaluated with adjustment for age, sex, hypertension, dyslipidemia, diabetes, obesity, current smoking status, and family history of heart disease in the first-degree relatives. RESULTS: In age- and sex-adjusted models, NAFLD was significantly associated with calcification in the coronary artery, carotid artery, thoracic aorta, celiac trunk, and superior mesenteric artery vascular beds (P < .05). However, adjustment for the traditional chronic venous disease risk factors attenuated the associations, except in the case of the thoracic aorta (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.09-1.78) and celiac trunk (OR, 2.05; 95% CI, 1.16-3.65). In addition, NAFLD was independently associated with multiarterial calcification (four or more [OR, 1.33; 95% CI, 1.01-1.74], five or more [OR, 1.46; 95% CI, 1.09-1.97], and six or more [OR, 1.58; 95% CI, 1.09-2.30] of eight evaluated arterial segments). CONCLUSIONS: The association between NAFLD and arterial calcification is mainly mediated by conventional risk factors. The independent association between NAFLD and calcification in the thoracic aorta and celiac trunk as well as in a larger number of vascular beds needs confirmation in future prospective studies in diverse populations.

Predictors of Change in the Ankle Brachial Index with Exercise.

OBJECTIVE: A 20% or greater decrease in the ankle brachial index (ABI) with exercise is suggestive of peripheral artery disease (PAD), and could identify patients with an increased mortality risk. The predictors of a change in the ABI with exercise have received little attention. METHODS: This was a cross-sectional analysis. Two hundred and sixty five participants of the San Diego Population Study with a resting ABI between 0.90 and 1.10 performed 50 heel raises and immediately had their ABIs measured again. The relationship between the change in the ABI with exercise and multiple potential risk prediction variables were examined using linear regression. In addition, the categorical percent change in the ABI with exercise was analysed by multinomial logistic regression. RESULTS: The mean age of participants was 71.8 years, and 80.4% were female. At rest, the average ABI was 1.04 (SD 0.04) before and 0.94 (SD 0.13) after exercise; a mean decrease of 9.5%. In analyses of ABI change as a continuous variable, higher age, any smoking history, and a diagnosis of chronic obstructive pulmonary disease (COPD) were associated with a significant decrease in the ABI with exercise (p = .01, .04, and .03, respectively). Categorical analyses of the risk factors associated with a 20% or greater ABI decrease with exercise confirmed these results. Congestive heart failure was associated with an increased ABI with exercise (p = .04) in continuous ABI change analyses only. CONCLUSIONS: Older age, a positive history of smoking, and a history of COPD were independently and significantly associated with a greater ABI decrease with exercise. These risk variables may help identify persons with subclinical PAD.

Ankle-brachial index predicts change over time in functional status in the San Diego Population Study.

BACKGROUND: Peripheral artery disease (PAD) affects millions of people, both in the U.S. and worldwide. Even when asymptomatic, PAD and the ankle-brachial index (ABI), the major clinical diagnostic criterion for PAD, are associated with decreased functional status and quality of life, as well as mobility impairment. Whether the ABI or change in the ABI predicts decline in functional status over time has not been previously assessed in a population-based setting. METHODS: Participants were 812 non-Hispanic white, African American, Hispanic, and Asian men and women from the San Diego Population Study (SDPS) who attended a baseline examination (1994-1998), and follow-up clinic examination approximately 11 years later. The Medical Outcomes Study 36-Item Short Form (SF-36) was obtained at both the baseline and follow-up examinations, and the summary performance score (SPS) at the follow-up examination. Associations of the baseline ABI and clinically relevant change in the ABI (<-0.15 vs ≥-0.15) with change in SF-36 scores over time were assessed using growth curve models, a type of mixed model that accounts for within participant correlation of measurements over time, and using linear regression for SPS. Models were adjusted for baseline age, sex, race/ethnicity, body mass index, ever smoking, physical activity, hypertension, diabetes, and dyslipidemia. RESULTS: Mean ± standard deviation (SD) for the baseline ABI was 1.11 ± 0.10, and 50.8 ± 9.0 for the baseline Physical Component Score (PCS), 50.1 ± 9.5 for the baseline Mental Component Score (MCS), and 11.2 ± 1.9 for the SPS at the follow-up examination. In fully adjusted models, each SD lower of the baseline ABI was significantly associated with an average decrease over time of 0.6 (95% confidence interval [CI], -1.1 to -0.1; P = .02) units on SF-36 PCS. Each SD lower of the baseline ABI was also significantly associated with an average decrease over time of 1.2 units (95% CI, -2.3 to -0.2; P = .02) on the SF-36 physical functioning subscale, and a decrease of 1.3 units (95% CI, -2.3 to -0.3; P = .01) on the SF-36 energy/vitality subscale in fully adjusted models. Baseline ABI was not significantly associated with change in the SF-36 MCS over time, or the SPS at the follow-up examination. Change in the ABI was not associated with SF-36 PCS, MCS, or the SPS. CONCLUSIONS: In this multiethnic population of healthy middle-aged community-living men and women, we showed that participants with a lower baseline ABI had declines in functional status over 11 years. Findings suggest that small differences in the ABI, even within the normal range, may identify subclinical lower extremity PAD, which in turn may help to identify individuals at risk for declining functional status with age.

Risk marker associations with venous thrombotic events: a cross-sectional analysis.

OBJECTIVE: To examine the interrelations among, and risk marker associations for, superficial and deep venous events-superficial venous thrombosis (SVT), deep venous thrombosis (DVT) and pulmonary embolism (PE). DESIGN: Cross-sectional analysis. SETTING: San Diego, California, USA. PARTICIPANTS: 2404 men and women aged 40-79 years from four ethnic groups: non-Hispanic White, Hispanic, African-American and Asian. The study sample was drawn from current and former staff and employees of the University of California, San Diego and their spouses/significant others. OUTCOME MEASURES: Superficial and deep venous events, specifically SVT, DVT, PE and combined deep venous events (DVE) comprising DVT and PE. RESULTS: Significant correlates on multivariable analysis were, for SVT: female sex, ethnicity (African-American=protective), lower educational attainment, immobility and family history of varicose veins. For DVT and DVE, significant correlates included: heavy smoking, immobility and family history of DVEs (borderline for DVE). For PE, significant predictors included immobility and, in contrast to DVT, blood pressure (BP, systolic or diastolic). In women, oestrogen use duration for hormone replacement therapy, in all and among oestrogen users, predicted PE and DVE, respectively. CONCLUSIONS: These findings fortify evidence for known risk correlates/predictors for venous disease, such as family history, hormone use and immobility. New risk associations are shown. Striking among these is an association of PE, but not DVT, to elevated BP: we conjecture PE may serve as cause rather than consequence. Future studies should evaluate the temporal direction of this association. Oxidative stress and cell energy compromise are proposed to explain and predict many risk factors, operating through cell-death mediated triggering of coagulation activation.

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.

Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis.

BACKGROUND: Lower extremity peripheral artery disease is the third leading cause of atherosclerotic cardiovascular morbidity, following coronary artery disease and stroke. This study provides the first comparison of the prevalence of peripheral artery disease between high-income countries (HIC) and low-income or middle-income countries (LMIC), establishes the primary risk factors for peripheral artery disease in these settings, and estimates the number of people living with peripheral artery disease regionally and globally. METHODS: We did a systematic review of the literature on the prevalence of peripheral artery disease in which we searched for community-based studies since 1997 that defined peripheral artery disease as an ankle brachial index (ABI) lower than or equal to 0·90. We used epidemiological modelling to define age-specific and sex-specific prevalence rates in HIC and in LMIC and combined them with UN population numbers for 2000 and 2010 to estimate the global prevalence of peripheral artery disease. Within a subset of studies, we did meta-analyses of odds ratios (ORs) associated with 15 putative risk factors for peripheral artery disease to estimate their effect size in HIC and LMIC. We then used the risk factors to predict peripheral artery disease numbers in eight WHO regions (three HIC and five LMIC). FINDINGS: 34 studies satisfied the inclusion criteria, 22 from HIC and 12 from LMIC, including 112,027 participants, of which 9347 had peripheral artery disease. Sex-specific prevalence rates increased with age and were broadly similar in HIC and LMIC and in men and women. The prevalence in HIC at age 45-49 years was 5·28% (95% CI 3·38-8·17%) in women and 5·41% (3·41-8·49%) in men, and at age 85-89 years, it was 18·38% (11·16-28·76%) in women and 18·83% (12·03-28·25%) in men. Prevalence in men was lower in LMIC than in HIC (2·89% [2·04-4·07%] at 45-49 years and 14·94% [9·58-22·56%] at 85-89 years). In LMIC, rates were higher in women than in men, especially at younger ages (6·31% [4·86-8·15%] of women aged 45-49 years). Smoking was an important risk factor in both HIC and LMIC, with meta-OR for current smoking of 2·72 (95% CI 2·39-3·09) in HIC and 1·42 (1·25-1·62) in LMIC, followed by diabetes (1·88 [1·66-2·14] vs 1·47 [1·29-1·68]), hypertension (1·55 [1·42-1·71] vs 1·36 [1·24-1·50]), and hypercholesterolaemia (1·19 [1·07-1·33] vs 1·14 [1·03-1·25]). Globally, 202 million people were living with peripheral artery disease in 2010, 69·7% of them in LMIC, including 54·8 million in southeast Asia and 45·9 million in the western Pacific Region. During the preceding decade the number of individuals with peripheral artery disease increased by 28·7% in LMIC and 13·1% in HIC. INTERPRETATION: In the 21st century, peripheral artery disease has become a global problem. Governments, non-governmental organisations, and the private sector in LMIC need to address the social and economic consequences, and assess the best strategies for optimum treatment and prevention of this disease. FUNDING: Peripheral Arterial Disease Research Coalition (Europe).

Biomarkers in peripheral arterial disease patients and near- and longer-term mortality.

BACKGROUND: Whether novel biomarkers improve risk prediction of mortality beyond standard cardiovascular disease (CVD) risk markers in peripheral arterial disease (PAD) patients, and whether any such prediction differs with length of follow-up, remains controversial. Our objective was to determine in patients with PAD whether novel biomarkers improve prediction of CVD mortality and total mortality. METHODS: A cohort of 397 patients who were referred to a vascular lab had PAD diagnosed by noninvasive testing. Fifty-eight percent also had coronary or cerebrovascular disease at baseline. Predictors of total, CVD, and non-CVD mortality were assessed with Cox proportional hazards models, and the incremental value of predictors was evaluated with both the C-statistic and the integrated discrimination improvement (IDI) index. RESULTS: Total mortality was 11% at 2-year follow-up and 65% at an average of 6.6-year of follow-up (maximum, 11.4 years). At 2 years, hs-CRP was a strong and significant predictor of mortality, with a hazard ratio (HR) of 1.56 per standard deviation (P = .006). However, at full follow up, standard CVD risk markers were significant (age, gender, ankle-brachial index, other CVD, and hypertension), but hs-CRP no longer showed a significant relationship (HR 1.12; P = .11). None of the other biomarkers studied showed a significant independent association with mortality. Hs-CRP improved the C-statistic and the IDI beyond standard risk markers at 2 years, but not at full follow-up. CONCLUSIONS: hs-CRP was a strong predictor of short-term mortality in this cohort of PAD patients, while standard risk markers were better at predicting longer-term mortality.

The association between elevated ankle systolic pressures and peripheral occlusive arterial disease in diabetic and nondiabetic subjects.

OBJECTIVE: The presence of a high ankle-brachial index (ABI) is related to stiff ankle arteries due to medial calcification. Recently, this condition has attracted new interest after reports of a worse cardiovascular prognosis, similar to a low ABI. We sought to compare risk factors contributing to a low (< or =0.90) and high (> or =1.40) ABI. Additionally, we hypothesized that in instances of high ABI, occlusive PAD may coexist. METHOD: This cross-sectional study was conducted at vascular laboratories in a university medical center. The subjects were 510 ambulatory patients (37% had diabetes) previously examined at our vascular laboratories and who responded positively to our invitation. We collected data on smoking, diabetes, hypertension, dyslipidemia, and cardiovascular disease history. The noninvasive assessment of lower limb arteries consisted of the measurement of ABI, toe-brachial index (TBI), and posterior tibial artery peak flow velocity (Pk-PT). A TBI >0.7 and a Pk-PT >10 cm/s were considered normal. RESULTS: High- and low-ABI were detected, respectively, in 2.1% and 57.8% of limbs. For a low ABI, age (odds ratio [OR], 1.29/10 y), pack-years (OR, 1.08/10 units), and hypertension (OR, 1.90) were independent significant (P < .001) factors. A strong association was found between diabetes and high ABI (OR, 16.0; P < .001). When ABI ranges were compared with TBI and Pk-PT results, those with ABI < or =0.90 and ABI > or =1.40 presented similar patterns of abnormalities. Pk-PT or TBI, or both, was abnormal in more than 80% of cases in both ABI < or =0.90 and > or =1.40 groups. The ABI vs TBI relationship appeared linear in nondiabetic patients, but had an inverted J-shape in diabetic patients, suggesting high ABI masked leg ischemia. CONCLUSIONS: Diabetes is the dominant risk factor for a high (> or =1.40) ABI. Occlusive PAD is highly prevalent in subjects with high ABI, and these subjects should be considered as PAD-equivalent.

Novel cardiovascular risk factors do not completely explain the higher prevalence of peripheral arterial disease among African Americans. The San Diego Population Study.

OBJECTIVES: This study was designed to determine whether novel cardiovascular disease (CVD) risk factors explain the high prevalence of peripheral arterial disease (PAD) among African Americans. BACKGROUND: Compared with Caucasians, African Americans have higher prevalence of PAD, an association that is not explained by traditional CVD risk factors. The degree to which novel CVD risk markers may explain the higher prevalence is uncertain. METHODS: A nested case-control study within the San Diego Population Study was performed. The study evaluated 104 persons with PAD and 164 age- and gender-matched control subjects who were employees of a large public university and participated in a peripheral artery and venous disease study. Nine novel CVD risk factors (homocysteine, lipoprotein (a), C-reactive protein, fibrinogen, tumor necrosis factor-alpha, von Willebrand factor, prothrombin fragment 1-2, D-dimer, and plasmin antiplasmin) were measured. Multivariable logistic regression evaluated whether these novel factors attenuated the association of African-American race and PAD and whether there was differential ethnic susceptibility to the novel factors. RESULTS: African Americans had 3-fold higher odds of PAD in age- and gender-matched models (odds ratio [OR] 3.1; 95% confidence interval [CI] 1.5 to 6.4; p < 0.01), an association that was modestly attenuated by adjustment for traditional (OR 2.4; 95% CI 0.9 to 6.1; p = 0.06) and novel CVD risk markers (OR 1.9; 95% CI 0.7 to 4.7; p = 0.18). Among the novel factors, the attenuation was primarily due to fibrinogen and lipoprotein (a). No interactions by novel CVD risk markers (both p values for interaction > or =0.24) were observed. CONCLUSIONS: Traditional and novel CVD risk factors only partially explain the higher prevalence of PAD among African Americans.

The association between lipoprotein-associated phospholipase A2 and cardiovascular disease and total mortality in vascular medicine patients.

INTRODUCTION: In some community-based studies, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been shown to be independently predictive of future fatal and nonfatal cardiovascular disease (CVD) events. We tested the hypothesis that Lp-PLA(2) is independently predictive of mortality in high-risk patients from a vascular laboratory. METHODS: Between 1990 and 1994, patients seen in the previous 10 years for noninvasive lower extremity arterial testing were invited to return for a vascular examination of the lower extremities. By medical record review, we identified 2265 eligible patients; of these, 508 returned for interviews, blood collection, and arterial examination and represent those who had survived, could be located, and were willing to participate. The 508 subjects were followed up for an average of 6.7 years until the end of the study period on December 31, 2001. Vital status was ascertained by multiple searches of the Social Security Death Index. The primary outcomes for this study were time to any, CVD, and coronary heart disease (CHD) mortality. RESULTS: The mean age was 68.2 years, 88% were men, 87% were non-Hispanic white, 39.1% were diagnosed with peripheral arterial disease only, 9.2% with other CVD only, and 28.5% with both peripheral arterial disease and other CVD. During the entire follow-up period, 299 (59.7%) patients died, 167 from CVD, of which 88 deaths were due to coronary heart disease. With adjustment for CVD risk factors and baseline peripheral arterial disease and other CVD, an increment of one standard deviation in Lp-PLA(2) activity was associated with a 40% higher risk for CHD mortality at 5 years of follow-up (P = .04). Additional adjustment for triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol reduced this association to nonsignificance (hazard risk, 1.12). CONCLUSION: In a vascular laboratory patient population, higher levels of LpPLA(2) mass and activity were not significantly associated with total, CVD, or CHD mortality at 5 years of follow-up and after adjustment for traditional CVD risk factors and the presence of PAD and other CVD at baseline. An apparent elevated risk of CHD death associated with elevated Lp-PLA2 was largely explained by associated elevations in lipids and lipoproteins.

Risk factors for chronic venous disease: the San Diego Population Study.

BACKGROUND: The etiology of chronic venous disease in the lower limbs is unclear, and very limited data are available on potential risk factors from representative population studies. METHODS: Participants in the San Diego Population Study, a free-living adult population randomly selected from age, sex, and ethnic strata, were systematically assessed for risk factors for venous disease. Categorization of normal, moderate, and severe disease was determined hierarchically through clinical examination and ultrasonography imaging by trained vascular technologists, who also performed anthropometric measures. An interviewer administered a questionnaire and an examination assessed potential risk factors for venous disease suggested by previous reports. RESULTS: In multivariable models, moderate venous disease was independently related to age, a family history of venous disease, previous hernia surgery, and normotension in both sexes. In men, current walking, the absence of cardiovascular disease, and not moving after sitting were also predictive. Additional predictors in women were weight, number of births, oophorectomy, flat feet, and not sitting. For severe disease, age, family history of venous disease, waist circumference, and flat feet were predictive in both sexes. In men, occupation as a laborer, cigarette smoking, and normotension were also independently associated with severe venous disease. Additional significant and independent predictors in women were hours standing, history of leg injury, number of births, and cardiovascular disease, but African American ethnicity was protective. Multiple other postulated risk factors for venous disease were not significant in multivariable analysis in this population. CONCLUSIONS: Although some risk factors for venous disease such as age, family history of venous disease, and findings suggestive of ligamentous laxity (hernia surgery, flat feet) are immutable, others can be modified, such as weight, physical activity, and cigarette smoking. Overall, these data provide modest support for the potential of behavioral risk-factor modification to prevent chronic venous disease.

The vital prognosis of subclavian stenosis.

OBJECTIVES: This study sought to assess the prognosis of subclavian stenosis (SS) as a potential marker of total and cardiovascular disease (CVD) mortality. BACKGROUND: Subclavian stenosis, diagnosed by a brachial systolic pressure difference (BSPD) > or =15 mm Hg, is associated with an increased prevalence of CVD risk factors. However, the association between SS and mortality is unknown. We hypothesized that a BSPD > or =15 mm Hg would predict an increased risk of CVD events. METHODS: We analyzed baseline and longitudinal data from 3 cohorts. Two were recruited from noninvasive vascular laboratories, and the third was a community-dwelling cohort. Multivariate survival models were used to test for an independent association of SS with total and CVD mortality. RESULTS: Baseline and follow-up data (mean 9.8 years) were complete in 1,778 participants. Subclavian stenosis was found in 157 (8.8%) subjects. Adjusted for age, gender, ethnicity, and cohort of origin, the presence of SS was significantly associated with increased total and CVD mortality (respectively, hazard ratio [HR] 1.42, p < 0.005; and HR 1.50, p = 0.05). This association persisted after adjustments for CVD risk factors (smoking pack-years, hypertension, diabetes, total/high-density lipoprotein cholesterol ratio, and body mass index) as well as lipid-lowering and antiplatelet therapies (HR 1.40, p < 0.01; and HR 1.57, p < 0.05 for total and CVD mortality, respectively). When any history of CVD or an ankle-brachial index <0.90 were added to the model, SS remained an independent predictor for total mortality (HR 1.34, p = 0.02), with a similar trend for CVD mortality (HR 1.43, p = 0.09). CONCLUSIONS: The presence of SS, easily diagnosed by comparing systolic pressures in the left and right arm, predicts total and CVD mortality independent of both CVD risk factors and existent CVD at baseline.

Risk factors for progression of peripheral arterial disease in large and small vessels.

BACKGROUND: Data on the natural history of peripheral arterial disease (PAD) are scarce and are focused primarily on clinical symptoms. Using noninvasive tests, we assessed the role of traditional and novel risk factors on PAD progression. We hypothesized that the risk factors for large-vessel PAD (LV-PAD) progression might differ from small-vessel PAD (SV-PAD). METHODS AND RESULTS: Between 1990 and 1994, patients seen during the prior 10 years in our vascular laboratories were invited for a new vascular examination. The first assessment provided baseline data, with follow-up data obtained at this study. The highest decile of decline was considered major progression, which was a -0.30 ankle brachial index decrease for LV-PAD and a -0.27 toe brachial index decrease for SV-PAD progression. In addition to traditional risk factors, the roles of high-sensitivity C-reactive protein, serum amyloid-A, lipoprotein(a), and homocysteine were assessed. Over the average follow-up interval of 4.6+/-2.5 years, the 403 patients showed a significant ankle brachial index and toe brachial index deterioration. In multivariable analysis, current smoking, ratio of total to HDL cholesterol, lipoprotein(a), and high-sensitivity C-reactive protein were related to LV-PAD progression, whereas only diabetes was associated with SV-PAD progression. CONCLUSIONS: Risk factors contribute differentially to the progression of LV-PAD and SV-PAD. Cigarette smoking, lipids, and inflammation contribute to LV-PAD progression, whereas diabetes was the only significant predictor of SV-PAD progression.

Exertional leg pain in patients with and without peripheral arterial disease.

BACKGROUND: Although exertional leg pain is a hallmark of peripheral arterial disease (PAD) and can occur in persons without PAD, symptom variation has received inadequate attention. METHODS AND RESULTS: Three cohort studies were combined for cross-sectional analysis. The San Diego Claudication Questionnaire assessed exertional leg pain. PAD was defined as ankle brachial index (ABI) < or =0.90 or history of lower-extremity revascularization. Of 3658 subjects, 3629 were analyzed after exclusions. Of these, 24.1% had PAD in 1 or both legs. There was a stepwise decrease in average ABI, from no pain to pain on exertion and rest, noncalf pain, atypical calf pain, and classic claudication (P=0.002). When stratified by PAD, this trend was no longer significant. Legs with ABIs >0.90 and revascularization had pain distributions intermediate between that of normal legs (ABI, 1.00 to 1.39) and legs with ABIs < or =0.90. Compared with normal legs, legs with low-normal (0.91 to 0.99) and high-normal (> or =1.40) ABIs had higher pain rates, suggesting borderline disease and vascular stiffness, respectively. Multivariable logistic regression models showed that ABI was a strong correlate of pain category throughout the ABI range. Independently of ABI, age, male sex, diabetes, smoking history, high body mass index, myocardial infarction, and previous revascularization were all significant correlates of exertional leg pain. CONCLUSIONS: No category of exertional leg pain was sufficiently sensitive or specific for routine PAD diagnosis. Legs with low-normal and high-normal ABIs appeared to have ischemic leg pain; thus, a "normal ABI" is likely to range from 1.00 to 1.39. In addition to ABI, several risk variables were independent correlates of exertional leg pain.

Subclavian artery stenosis: prevalence, risk factors, and association with cardiovascular diseases.

OBJECTIVES: The objective was to assess the prevalence of subclavian artery stenosis (SS) in four cohorts (two free-living and two clinical populations) and determine both risk factors for this condition and the association with other cardiovascular conditions. BACKGROUND: The prevalence of SS in the general population is unknown, and its association with risk factors and other cardiovascular diseases is not well-established. METHODS: A total of 4,223 subjects (2,975 from two free-living cohorts and 1,248 from two clinical cohorts) were included in this cross-sectional analysis. Subclavian artery stenosis was defined as > or =15 mm Hg interarm pressure difference. RESULTS: The prevalence of SS was 1.9% in the free-living cohorts and 7.1% in the clinical cohorts; SS was significantly (p < 0.05) associated with past smoking (odds ratio [OR] = 1.80), current smoking (OR = 2.61), and higher levels of systolic blood pressure (OR = 1.90 per 20 mm Hg). Higher levels of high-density lipoprotein (HDL) cholesterol were inversely and significantly associated with SS (OR = 0.87 per 10 mg/dl). In regression analyses relating SS to other cardiovascular diseases, the only significant finding was with peripheral arterial disease (PAD) (OR = 5.11, p < 0.001). CONCLUSIONS: Significant SS is present in approximately 2% of the free-living population and 7% of the clinical population. Additionally, SS is correlated with current and past smoking histories, systolic blood pressure, HDL levels (inversely), and the presence of PAD. These findings suggest that bilateral brachial blood pressure measurements should routinely be performed in patients with an elevated risk profile, both to screen for SS, and to avoid missing a hypertension or PAD diagnosis because of unilateral pressure measurement in an obstructed arm.

Quality of life in patients with chronic venous disease: San Diego population study.

BACKGROUND: Chronic venous disease in the lower extremities may have a substantial effect on functioning and quality of life. We report quality of life data for an ethnically diverse population that had been systematically evaluated for venous disease. SUBJECTS: Current and retired employees from a large public university were randomly selected within strata of age, sex, and ethnicity. The sample included 2404 men and women ages 40 to 79 years. MEASURES: Quality of life was measured with the Medical Outcomes Study 36-Item Short Form (SF-36). Venous disease of the lower extremities was evaluated with two methods. Visual inspection was used to place participants into four categories: normal, telangiectasias and spider veins, varicose veins, and trophic changes. Duplex ultrasound scanning was used to place participants into three categories: normal, superficial venous disease, and deep vein disease. RESULTS: There were significant associations between quality of life and venous disease severity as assessed with both visual and ultrasound methods. These differences were observed for both men and women for functional scales of the SF-36. The relationships were significant, and were graded with degree of disease severity. Differences categories were not statistically significant for the mental health scales of the SF-36. CONCLUSION: Chronic venous disease in the lower extremities has a substantial effect on physical health aspects of quality of life but not on mental health components.