The ClaudicatioNet concept: design of a national integrated care network providing active and healthy aging for patients with intermittent claudication.

INTRODUCTION: Intermittent claudication (IC) is a manifestation of peripheral arterial occlusive disease (PAOD). Besides cardiovascular risk management, supervised exercise therapy (SET) should be offered to all patients with IC. Outdated guidelines, an insufficient number of specialized physiotherapists (PTs), lack of awareness of the importance of SET by referring physicians, and misguided financial incentives all seriously impede the availability of a structured SET program in The Netherlands. DESCRIPTION OF CARE PRACTICE: By initiating regional care networks, ClaudicatioNet aims to improve the quality of care for patients with IC. Based on the chronic care model as a conceptual framework, these networks should enhance the access, continuity, and (cost) efficiency of the health care system. With the aid of a national database, health care professionals will be able to benchmark patient results while ClaudicatioNet will be able to monitor quality of care by way of functional and patient reported outcome measures. DISCUSSION: The success of ClaudicatioNet is dependent on several factors. Vascular surgeons, general practitioners and coordinating central caregivers will need to team up and work in close collaboration with specialized PTs. A substantial task in the upcoming years will be to monitor the quality, volume, and distribution of ClaudicatioNet PTs. Finally, misguided financial incentives within the Dutch health care system need to be tackled. CONCLUSION: With ClaudicatioNet, integrated care pathways are likely to improve in the upcoming years. This should result in the achievement of optimal quality of care for all patients with IC.

Applicability of the ankle-brachial-index measurement as screening device for high cardiovascular risk: an observational study.

BACKGROUND: Screening with ankle-brachial index (ABI) measurement could be clinically relevant to avoid cardiovascular events in subjects with asymptomatic atherosclerosis. To assess the practical impact of guidelines regarding the use of ABI as a screening tool in general practice, the corresponding number needed to screen, including the required time investment, and the feasibility of ABI performance, was assessed. METHODS: An observational study was performed in the setting of 955 general practices in the Netherlands. Overall, 13,038 subjects of ≥55 years presenting with symptoms of intermittent claudication and/or presenting with ≥ one vascular risk factor were included. Several guidelines recommend the ABI as an additional measurement in selected populations for risk assessment for cardiovascular morbidity. RESULTS: Screening of the overall population of ≥50 years results in ≈ 862 subjects per general practice who should be screened, resulting in a time-requirement of approximately 6 weeks of full time work. Using an existing clinical prediction model, 247 patients per general practice should be screened for PAD by ABI measurement. CONCLUSION: Screening the entire population of ≥50 years will in our opinion not be feasible in general practice. A more rationale and efficient approach might be screening of subsets of the population of ≥55 years based on a clinical prediction model.

Lifetime endogenous estrogen exposure and electrocardiographic frontal T axis changes in postmenopausal women.

OBJECTIVE: The protective effect of endogenous estrogens in cardiovascular disease may in part originate from effects of circulating estrogens on the electrophysiological properties of the myocardium. The aim of this study was to investigate the relation between reproductive factors and the electrocardiographic frontal T axis in postmenopausal women. DESIGN: Cohort study. SETTING: The study was conducted at the University Medical Center Utrecht. PATIENTS: In total, 998 postmenopausal women were included. MAIN OUTCOMES: Information of women's reproductive life was obtained by a questionnaire. Electrocardiographic frontal T axes were categorized as normal (25-65 degrees) or abnormal (-180 degrees to 24 degrees and 66-180 degrees). Logistic regression analysis was used to assess the relationship between reproductive factors and the frontal T axis. Moreover, the effect of the lifetime cumulative number of menstrual cycles, a composite measure of all reproductive factors, on the frontal T axis was investigated. RESULTS: The mean age was 66.0 (+/-5.6) years and 15.3% had T-axes abnormalities. Later menopausal age decreased the risk on frontal T-axis abnormalities; the multivariable adjusted odds ratio was 0.97 (95% CI: 0.94-0.99) per year increasing menopause. For the lifetime cumulative number of menstrual cycles the age-adjusted odds ratio was 0.84 (95% CI: 0.75-0.99) per 100 menstrual cycles increase. CONCLUSIONS: Later age at menopause and increasing lifetime cumulative number of menstrual cycles decreased the risk on frontal T-axis changes. This supports the view that estrogens may protect against ventricular repolarization disturbances.

High dietary menaquinone intake is associated with reduced coronary calcification.

BACKGROUND: Dietary vitamin K is thought to decrease risk of cardiovascular disease by reducing coronary calcification, but inconsistent results are reported. This may be due to different effects of vitamin K(1) (phylloquinone) and vitamin K(2) (menaquinone, MK), but few studies included both. METHODS: We investigated the association of intake of phylloquinone and menaquinone, including its subtypes (MK4-MK10), with coronary calcification in a cross-sectional study among 564 post-menopausal women. Phylloquinone and menaquinone intake was estimated using a food-frequency questionnaire. RESULTS: Sixty-two percent (n=360) of the women had coronary calcification based on 1.5-mm thick slices. Phylloquinone intake was not associated with coronary calcification with a relative risk (RR) of 1.17 (95%-confidence interval: 0.96-1.42; p(trend)=0.11) of the highest versus lowest quartile. Menaquinone intake was associated with decreased coronary calcification with an RR of 0.80 (95%-CI: 0.65-0.98; p(trend)=0.03). CONCLUSION: This study shows that high dietary menaquinone intake, but probably not phylloquinone, is associated with reduced coronary calcification. Adequate menaquinone intakes could therefore be important to prevent cardiovascular disease.

Reproductive factors, metabolic factors, and coronary artery calcification in older women.

OBJECTIVE: Metabolic disturbances may explain the increased cardiovascular risk associated with reproductive factors. This cohort study investigated the relationship between reproductive factors and coronary artery calcification in elderly women and whether this relationship could be explained by metabolic disturbances. DESIGN: In total, 568 postmenopausal women were included in this cross-sectional study. Information about the women's reproductive life was obtained by a questionnaire. Metabolic factors were measured during a single visit. Coronary artery calcification was assessed with a multislice computed tomography scanner and dichotomized as absent or present. Logistic regression analysis was used to assess the relationship between reproductive factors and coronary artery calcification. Crude and multivariate adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. In addition, ORs were adjusted for several metabolic and cardiovascular risk factors. RESULTS: The mean age was 66.9 (+/- 5.5) years. Women with a history of irregular menstrual cycle lengths, as opposed to women with a history of regular menstrual cycles (26-30 d), had an increased risk of coronary artery calcification; multivariate-adjusted OR = 2.73 (95%CI: 1.24-5.98). Four or more pregnancies, compared with never pregnant, yielded an multivariate-adjusted OR of 1.89 (95% CI: 1.00-3.58). Having four children or more, compared with having no children, yielded a multivariate-adjusted OR of 1.97 (95% CI: 1.00-3.89). Adjustment for metabolic factors and other cardiovascular risk factors did not fully explain theses relationships. CONCLUSION: Multigravidity (more than four pregnancies), multiparity (more than four births), and irregular menstrual cycle lengths were related to an increased risk of coronary artery disease. These associations could not be explained by metabolic abnormalities.

Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women.

AIMS: To determine whether peri-coronary epicardial adipose tissue (EAT) is associated with vascular risk factors and coronary atherosclerosis. METHODS AND RESULTS: In this study, 573 healthy post-menopausal women underwent a cardiac CT scan to assess coronary calcification. Peri-coronary EAT thickness was measured in the areas of right coronary artery (RCA), left anterior descending (LAD) artery, and left circumflex (LCX) coronary artery. Average EAT thickness was 16.5 +/- 4.3 mm (range 5.9-34.6) in the RCA area, 6.4 +/- 2.2 mm (range 2.0-14.0) in the LAD area, and 10.8 +/- 3.0 mm (range 2.8-29.1) in the LCX area. Overall average thickness was 11.2 +/- 2.2 mm (range 5.4-19.1). EAT was positively related to age (P = 0.002). In age-adjusted linear regression models, EAT was positively related to weight (P< 0.001), waist circumference (P< 0.001), waist-to-hip ratio (P< 0.001), body mass index (P< 0.001), glucose (P< 0.001), triglycerides (P = 0.001), use of anti-hypertensive drugs (P = 0.007), and systolic blood pressure (P = 0.034), and inversely to HDL cholesterol (P = 0.005). In multivariable models, age, weight, waist circumference, smoking, and glucose were the main determinants of EAT. EAT showed a graded relation with coronary calcification (P = 0.026). CONCLUSION: EAT is strongly related to vascular risk factors and coronary calcification. Our findings support the hypothesis that EAT affects coronary atherosclerosis and possibly coronary risk.

No added value of age at menopause and the lifetime cumulative number of menstrual cycles for cardiovascular risk prediction in postmenopausal women.

BACKGROUND: The aim of the present study was to investigate the added value of age at menopause and the lifetime cumulative number of menstrual cycles in cardiovascular risk prediction in postmenopausal women. METHODS: This study included 971 women. The ankle-arm index was used as a proxy for cardiovascular morbidity and mortality. The ankle-arm index was calculated for each leg by dividing the highest ankle systolic blood pressure by the highest brachial systolic blood pressure. A cut-off value of 0.95 was used to differentiate between low and high risk women. Three cardiovascular risk models were constructed. In the initial model all classical predictors for cardiovascular disease were investigated. This model was then extended by age at menopause or the lifetime cumulative number of menstrual cycles to test their added value for cardiovascular risk prediction. Differences in discriminative power between the models were investigated by comparing the area under the receiver operating characteristic (ROC) curves. RESULTS: The mean age was 66.0 (+/-5.6) years. The 6 independent predictors for cardiovascular disease were age, systolic blood pressure, total to HDL cholesterol ratio, current smoking, glucose level, and body mass index > or =30 kg/m(2). The ROC area was 0.69 (0.64-0.73) and did not change when age at menopause or the lifetime cumulative number of menstrual cycles was added. CONCLUSIONS: The findings in this study among postmenopausal women did not support the view that age at menopause or a refined estimation of lifetime endogenous estrogen exposure would improve cardiovascular risk prediction as approximated by the ankle-arm index.

A clinical prediction model for the presence of peripheral arterial disease--the benefit of screening individuals before initiation of measurement of the ankle-brachial index: an observational study.

Measurement of the ankle-brachial index (ABI) can provide important information about the presence of subclinical atherosclerosis. Performing the ABI in the overall population is not feasible, but it can be used in a selected population. A simple prediction rule could be of much use to estimate the risk of an abnormal ABI. This was designed as an observational study in the setting of 955 general practices in The Netherlands. A total of 7454 patients aged > or = 55 years presenting with at least one vascular risk factor (smoking, hypertension, diabetes, and hypercholesterolemia) and no complaints of intermittent claudication were included. Patients were selected by the general practitioner during visiting hours and from medical records. Main outcome measures included the prevalence of PAD, defined as an ABI below 0.9, which was related to vascular risk factors using regression analyses on which the PREVALENT clinical prediction model was developed. The overall prevalence of PAD was 18.4%. Since the treatment of individuals with a history of coronary heart disease and cerebrovascular disease will not be influenced by the finding of asymptomatic PAD, these individuals were not taken into account for the development of the clinical prediction model. Analyses showed a significantly increased risk for PAD with increasing age, smoking, and hypertension. The clinical prediction model giving risk factor points per factor (age: 1 point per 5 years starting at 55 years; ever smoked: 2 points; currently smoking: 7 points; and hypertension: 3 points), showed a proportional increase of the PAD prevalence with each increasing risk profile (range: 7.0-40.6%). In conclusion, based on the PREVALENT clinical prediction model, the general practitioner is able to identify a high-risk population in which measurement of ABI is useful.

High blood pressure in pregnancy and coronary calcification.

A considerable proportion of pregnant women develop high blood pressure in pregnancy. Although it is assumed that this condition subsides after pregnancy, many of these women develop the metabolic syndrome later in life and are at increased risk to develop coronary heart disease. Atherosclerosis development is considered in between risk factors and occurrence of vascular symptoms. We set out to cross-sectionally study the relation of high blood pressure during pregnancy with risk of coronary calcification. The study population was composed 491 healthy postmenopausal women selected from a population-based cohort study. Information on high blood pressure during pregnancy was obtained using a questionnaire. Between 2004 and 2005, the women underwent a multidetector computed tomography (Philips Mx 8000 IDT 16) to assess coronary calcium. The Agatston score, volume, and mass measurements were used to quantify coronary calcium. A total of 30.7% of the women reported to have had high blood pressure in pregnancy. Body mass index (odds ratio [OR]: 1.05; 95% CI: 1.01 to 1.09) and diastolic blood pressure (OR: 1.03; 95% CI: 1.01 to 1.05) were significantly related to a history of high blood pressure in pregnancy. Age was significantly related to increased coronary calcification. Women with a history of high blood pressure during pregnancy had a 57% increased risk of having coronary calcification compared with those women without this condition (OR: 1.57; 95% CI: 1.04 to 2.37). After adjusting for age, the relation did not change (OR: 1.64; 95% CI: 1.07 to 2.53). We concluded that high blood pressure during pregnancy is associated with an increased risk of coronary calcification later in life.

Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule.

BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease.

Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis.

OBJECTIVE: Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause. DESIGN: A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking. RESULTS: The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01). CONCLUSIONS: Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.

Smoking and the patency of lower extremity bypass grafts: a meta-analysis.

OBJECTIVE: Smoking is the major risk factor associated with the development and progression of peripheral arterial disease (PAD). To establish the best estimate of the effect of smoking, smoking cessation, and the dose-response relationship on the patency of lower extremity bypass grafts, we performed a systematic review. METHODS: A search of medical articles and reviews relating to the influence of smoking on the patency of arterial reconstructive grafts in patients with PAD was made. Studies considered for inclusion were those that evaluated the influence of smoking on the primary, secondary, or cumulative patency rates of arterial reconstructive surgery in the lower extremities in patients with PAD. Primary data were used to calculate summary estimates with standard meta-analysis techniques. RESULTS: The 29 eligible studies included 4 randomized clinical trials, 12 prospective studies, and 13 retrospective studies. The effect of smoking on graft patency in the randomized clinical trials and other prospective studies had a 3.09-fold (2.34 to 4.08; P < .00001) increase in graft failure. A comparison of patency rates among all studies that used autogenous or polyester grafts showed no difference. A clear dose-response relationship was present, with a decreased patency in heavy smokers compared with moderate smokers. Smoking cessation restores patency rates toward the never smokers group. CONCLUSION: Continued smoking after lower limb bypass surgery results in a threefold increased risk of graft failure. Smoking cessation, even if instigated after the operation, restored graft patency towards the patency of never smokers. These results indicate that adequate smoking cessation strategies in patients eligible for lower limb bypass surgery are of utmost importance.

Combined training of GPs and practice-assistants on peripheral arterial disease: positive effects after six months.

OBJECTIVES: To improve the use of the ankle-brachial index (ABI) measurement, and management of patients with peripheral arterial disease (PAD) a combined training, targeting GPs and practice assistants (PAs) was developed. To measure the effect of the combined training on the management of patients with PAD, a cross-sectional study was performed. METHODS: Fifty consecutive patients referred by GPs to a vascular surgery out-patient clinic were analysed. Six months after the training an additional fifty patients were included. In all patients the ABI measurement, risk factor management, and treatment as performed by the GP, prior to referral, were analysed. RESULTS: The measurement of the ABI significantly increased from 10% before the training to 53% after the training (GPs with training: 83%, GPs without training: 35%; P: 0.001). The referral of patients with actual PAD significantly increased from 32% before the training to 70% after the training (GPs with training: 83%, GPs without training: 59%; P: 0.05). The presence and treatment of risk factors did not differ between the groups. CONCLUSIONS: Within the limitations of a before and after study the combined training of GPs and PAs appears to be an effective method to increase ABI measurements and significantly improve adequate diagnostics.

Influence of smoking on incidence and prevalence of peripheral arterial disease.

OBJECTIVE: Many studies have been published regarding the influence of smoking on the incidence and prevalence of peripheral arterial disease (PAD). A systematic review was performed to establish the magnitude of the effect of smoking on the development of PAD, and a possible dose-response relationship. METHODS: English-language articles were reviewed by 2 observers using a standardized form, and were summarized in tabular form. Data were extracted by 2 independent observers. Where possible, outcome data, expressed in terms of prevalence or incidence, were recalculated as odds ratio or relative risk, with never-smokers as the reference group, or if this was not available the nonsmoker group. Most studies did not provide primary data. Therefore the weighted means were reported as a summary estimate, provided that a funnel plot between sample size and observed effect size made publication bias unlikely. RESULTS: Sixteen articles describing 17 studies were included in the analysis. Four of the studies were prospective, and 13 were cross-sectional. The prevalence of symptomatic PAD was increased 2.3-fold in current smokers. Even in former smokers the prevalence was substantially increased by a factor of 2.6. A clear dose-response relationship, with a strong increase in risk for PAD in heavy smokers was observed. In countries where approximately 30% of the population are smokers, 50% of PAD can be attributed to smoking. CONCLUSIONS: Smoking is a potent risk factor for symptomatic PAD, with an important and consistent dose-response relationship. With the persistence of high risk for PAD in former smokers, tobacco control programs should continue to advocate smoking cessation, but focus even more on preventing future generations from ever starting to smoke.