David Pittrow

High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study

We aimed to obtain reliable data on the epidemiology, co-morbidities and risk factor profile of peripheral arterial disease (PAD) in general medical practise. In the cross-sectional part of the observational German Epidemiological Trial on Ankle Brachial Index (getABI study), 344 general practitioners throughout Germany determined the ABI of consecutive, unselected patients aged 65 years or older with bilateral Doppler ultrasound measurements. Additional assessments comprised patient history with the focus on atherothrombotic diseases, physical examination, and the WHO questionnaire on intermittent claudication. A total of 6880 patients were included (42.0% male, mean age 72.5 years, mean body mass index 27.3 kg/m(2), mean systolic/diastolic blood pressure 143.7/81.3 mmHg). The prevalence of PAD for men/women as indicated by an ankle brachial index (AB1)<0.9 was 19.8/16.8%. Patients with PAD were slightly older than patients without PAD, suffered more frequently from diabetes (36.6 vs. 22.6%; adjusted OR: 1.8), hypertension (78.8 vs. 61.6%; OR: 2.2), lipid disorders (57.2 vs. 50.7%; OR: 1.3) and other coexisting atherothrombotic diseases (any cerebrovascular event: 15.0 vs. 7.6%; OR: 1.8; any cardiovascular event: 28.9 vs. 17.0%; OR: 1.5). The data highlight the high prevalence of PAD in primary care. PAD patients are characterised by a high co-morbidity, particularly with regard to other manifestations of atherothrombosis. Doppler ultrasound measurement for ABI determinations is a non-invasive, inexpensive, reliable tool in primary care and enables GPs to identify patients at risk of PAD.

Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic Peripheral Artery Disease

Background— Our aim was to assess the mortality and vascular morbidity risk of elderly individuals with asymptomatic versus symptomatic peripheral artery disease (PAD) in the primary care setting. Methods and Results— This prospective cohort study included 6880 representative unselected patients ≥65 years of age with monitored follow-up over 5 years. According to physician diagnosis, 5392 patients had no PAD, 836 had asymptomatic PAD (ankle brachial index <0.9 without symptoms), and 593 had symptomatic PAD (lower-extremity peripheral revascularization, amputation as a result of PAD, or intermittent claudication symptoms regardless of ankle brachial index). The risk of symptomatic compared with asymptomatic PAD patients was significantly increased for the composite of all-cause death or severe vascular event (myocardial infarction, coronary revascularization, stroke, carotid revascularization, or lower-extremity peripheral vascular events; hazard ratio, 1.48; 95% confidence interval, 1.21 to 1.80) but not for all-cause death alone (hazard ratio, 1.13; 95% confidence interval, 0.89 to 1.43), all-cause death/myocardial infarction/stroke (excluding lower-extremity peripheral vascular events and any revascularizations; hazard ratio, 1.18; 95% confidence interval, 0.92 to 1.52), cardiovascular events alone (hazard ratio, 1.20; 95% confidence interval, 0.89 to 1.60), or cerebrovascular events alone (hazard ratio, 1.33; 95% confidence interval, 0.80 to 2.20). Lower ankle brachial index categories were associated with increased risk. PAD was a strong factor for the prediction of the composite end point in an adjusted model. Conclusions— Asymptomatic PAD diagnosed through routine screening in the offices of primary care physicians carries a high mortality and/or vascular event risk. Notably, the risk of mortality was similar in symptomatic and asymptomatic patients with PAD and was significantly higher than in those without PAD. In the primary care setting, the diagnosis of PAD has important prognostic value.

The Predictive Value of Different Measures of Obesity for Incident Cardiovascular Events and Mortality

CONTEXT To date, it is unclear which measure of obesity is the most appropriate for risk stratification. OBJECTIVE The aim of the study was to compare the associations of various measures of obesity with incident cardiovascular events and mortality. DESIGN AND SETTING We analyzed two German cohort studies, the DETECT study and SHIP, including primary care and general population. PARTICIPANTS A total of 6355 (mean follow-up, 3.3 yr) and 4297 (mean follow-up, 8.5 yr) individuals participated in DETECT and SHIP, respectively. INTERVENTIONS We measured body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) and assessed cardiovascular and all-cause mortality and the composite endpoint of incident stroke, myocardial infarction, or cardiovascular death. RESULTS In both studies, we found a positive association of the composite endpoint with WHtR but not with BMI. There was no heterogeneity among studies. The relative risks in the highest versus the lowest sex- and age-specific quartile of WHtR, WC, WHR, and BMI after adjustment for multiple confounders were as follows in the pooled data: cardiovascular mortality, 2.75 (95% confidence interval, 1.31-5.77), 1.74 (0.84-3.6), 1.71 (0.91-3.22), and 0.74 (0.35-1.57), respectively; all-cause mortality, 1.86 (1.25-2.76), 1.62 (1.22-2.38), 1.36 (0.93-1.69), and 0.77 (0.53-1.13), respectively; and composite endpoint, 2.16 (1.39-3.35), 1.59 (1.04-2.44), 1.49 (1.07-2.07), and 0.57 (0.37-0.89), respectively. Separate analyses of sex and age groups yielded comparable results. Receiver operating characteristics analysis yielded the highest areas under the curve for WHtR for predicting these endpoints. CONCLUSIONS WHtR represents the best predictor of cardiovascular risk and mortality, followed by WC and WHR. Our results discourage the use of the BMI.

Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry.

BACKGROUND Originally reported to occur predominantly in younger women, idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in elderly patients. We aimed to describe the characteristics of such patients and their survival under clinical practice conditions. METHODS Prospective registry in 28 centers in 6 European countries. Demographics, clinical characteristics, hemodynamics, treatment patterns and outcomes of younger (18-65 years) and elderly (>65 years) patients with newly diagnosed IPAH (incident cases only) were compared. RESULTS A total of 587 patients were eligible for analysis. The median (interquartile, [IQR]) age at diagnosis was 71 (16) years. Younger patients (n=209; median age, 54 [16] years) showed a female-to-male ratio of 2.3:1 whereas the gender ratio in elderly patients (n=378; median age, 75 [8] years) was almost even (1.2:1). Combinations of PAH drugs were widely used in both populations, albeit less frequently in older patients. Elderly patients were less likely to reach current treatment targets (6 min walking distance>400 m, functional class I or II). The survival rates 1, 2, and 3 years after the diagnosis of IPAH were lower in elderly patients, even when adjusted for age- and gender-matched survival tables of the general population (p=0.006 by log-rank analysis). CONCLUSIONS In countries with an aging population, IPAH is now frequently diagnosed in elderly patients. Compared to younger patients, elderly patients present with a balanced gender ratio and different clinical features, respond less well to medical therapy and have a higher age-adjusted mortality. Further characterization of these patients is required. CLINICAL TRIALS REGISTRATION NCT01347216.

High prevalence and poor control of hypertension in primary care: cross-sectional study.

Objective To report: (1) on the background, design and methods of the Hypertension and Diabetes Risk Screening and Awareness (HYDRA) study, (2) on the point prevalence of hypertension in primary care and (3) on the proportion of treated, controlled, and uncontrolled hypertension. Design Cross-sectional point prevalence study. Setting Representative nationwide sample of 1912 primary care practices in Germany. Participants A total of 45 125 unselected primary care attendees. Main outcome measures Prevalence of hypertension based on doctors diagnosis, self-reported diagnosis, and blood pressure (BP) measurements. Results A total of 39% of all patients and 67% of patients aged 60 years or older, respectively, were diagnosed by their doctors as having hypertension. Eighty-four percent of diagnosed patients were on antihypertensive medication, 57% of which were rated by the physician as well controlled. When hypertension was defined as either current BP levels ⩾ 140/90 mmHg and/or current antihypertensive medication, the total point prevalence increased to 50%, while treatment and control rates (BP < 140/90 mmHg) dropped to 64 and 19%, respectively. Conclusions Extrapolation of these findings to the entire primary care patient population seen in the over 20 000 primary care practices in Germany suggests that on an average day, over 700 000 patients with elevated BP are seen by primary care physicians, but that only around 132 000 of these patients are well controlled. Thus, this study not only documents the enormous burden of hypertensive patients in the primary health system, but also highlights the alarming lack of BP control in the vast majority of hypertensive patients.

Anticoagulation and Survival in Pulmonary Arterial Hypertension Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)

Background— For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). Methods and Results— We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival (P=0.006) in patients on anticoagulation compared with patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant (P=0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95% confidence interval, 0.66–0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. Conclusions— The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01347216.BACKGROUND: For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). METHODS AND RESULTS: We analyzed data from COMPERA, an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1,283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year-survival (p=0.006) in patients on anticoagulation compared to patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant (p=0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio 0.79, 95% confidence interval 0.66 to 0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. CONCLUSIONS: The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. CLINICAL TRIALS REGISTRATION INFORMATION: www.clinicaltrials.gov. Identifier: NCT01347216.

Cardiovascular risk factors in primary care: methods and baseline prevalence rates - the DETECT program

ABSTRACT Objectives: DETECT is an epidemiological study in primary care to examine (a) the prevalence rates and comorbidity of diabetes mellitus, hypertension, hyperlipidaemia and coronary heart disease (CHD), and associated conditions; (b) the frequency of behavioural and clinical risk factors for onset and progression; (c) the 12-month course and outcome; and (d) the met and unmet needs for these patients. Methods: Three-stage, cross-sectional clinical-epidemiological study with a prospective-longitudinal component in a nationally representative sample of N = 3795 primary care settings [response rate (RR): 60.2%] and N = 55 518 patients (RR: 95.5%). Patients completed a standardized assessment, including questionnaires for patients and the physician and diagnostic screening measures (i.e. blood pressure, heart rate, body mass index and waist circumference assessments). A subsample of patients (N = 7519) also completed a standardized laboratory screening program and was followed-up after 12 months. Data were weighted to adjust for non-response, regional distribution and attrition. Results: (1) Doctors and patients sample can be regarded as representative for primary care settings in Germany. (2) The clinician-rated point prevalence of hypertension is highest (35.5%), followed by hyperlipidaemia (29.1%), diabetes (14.1%) and CHD (12.1%); prevalence rates of each disorder as well as their co-incidence rates increase markedly with age. (3) The vast majority (78%) of all patients revealed multiple (3+) behavioural and clinical risk factors. Conclusion: The findings of DETECT underline the considerable burden for primary care doctors in managing a highly morbid patient population, with predominantly complex risk factor constellations, in routine care. Our data provide, in unprecedented detail, a basis for calculating age-, gender- and risk-group-adjusted risk-factor profiles in routine care.

Anticoagulation and Survival in Pulmonary Arterial Hypertension

Background— For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). Methods and Results— We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival (P=0.006) in patients on anticoagulation compared with patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant (P=0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95% confidence interval, 0.66–0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. Conclusions— The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01347216.BACKGROUND: For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). METHODS AND RESULTS: We analyzed data from COMPERA, an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1,283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year-survival (p=0.006) in patients on anticoagulation compared to patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant (p=0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio 0.79, 95% confidence interval 0.66 to 0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. CONCLUSIONS: The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. CLINICAL TRIALS REGISTRATION INFORMATION: www.clinicaltrials.gov. Identifier: NCT01347216.

Low-grade albuminuria and cardiovascular risk : what is the evidence?

Microalbuminuria (MA), conventionally defined as a urinary albumin excretion (UAE) of 30–300 mg/day, is recognised as a marker of endothelial dysfunction. Furthermore, it represents an established risk factor for cardiovascular morbidity and mortality and for end-stage renal disease in individuals with an adverse cardiovascular risk profile. It is common in the general population, particularly in patients with diabetes mellitus or arterial hypertension. There is growing evidence from prospective observational trials that UAE levels well below the current MA threshold (“lowgrade MA”) are also associated with an increased risk of incident cardiovascular disease and allcause mortality. Even in apparently healthy individuals (without diabetes or hypertension), such an association has been shown. As albuminuria screening assays that are reliable even in the lower ranges are commercially available, there may be an important clinical role for MA in disease screening, comparable to the role of blood pressure and lipid screening. MA is modifiable, and the inhibition of the renin-angiotensin system by ACE inhibitors and AT1 receptor antagonists has been shown to result in a lower incidence of cardiovascular events.

Peripheral Arterial Disease as an Independent Predictor for Excess Stroke Morbidity and Mortality in Primary-Care Patients: 5-Year Results of the getABI Study

Background:There is controversial evidence with regard to the significance of peripheral arterial disease (PAD) as an indicator for future stroke risk. We aimed to quantify the risk increase for mortality and morbidity associated with PAD. Methods:In an open, prospective, noninterventional cohort study in the primary care setting, a total of 6,880 unselected patients ≧65 years were categorized according to the presence or absence of PAD and followed up for vascular events or deaths over 5 years. PAD was defined as ankle-brachial index (ABI) <0.9 or history of previous peripheral revascularization and/or limb amputation and/or intermittent claudication. Associations between known cardiovascular risk factors including PAD and cerebrovascular mortality/events were analyzed in a multivariate Cox regression model. Results:During the 5-year follow-up [29,915 patient-years (PY)], 183 patients had a stroke (incidence per 1,000 PY: 6.1 cases). In patients with PAD (n = 1,429) compared to those without PAD (n = 5,392), the incidence of all stroke types standardized per 1,000 PY, with the exception of hemorrhagic stroke, was about doubled (for fatal stroke tripled). The corresponding adjusted hazard ratios were 1.6 (95% confidence interval, CI, 1.1–2.2) for total stroke, 1.7 (95% CI 1.2–2.5) for ischemic stroke, 0.7 (95% CI 0.2–2.2) for hemorrhagic stroke, 2.5 (95% CI 1.2–5.2) for fatal stroke and 1.4 (95% CI 0.9–2.1) for nonfatal stroke. Lower ABI categories were associated with higher stroke rates. Besides high age, previous stroke and diabetes mellitus, PAD was a significant independent predictor for ischemic stroke. Conclusions:The risk of stroke is substantially increased in PAD patients, and PAD is a strong independent predictor for stroke.