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More stringent blood pressure (BP) goals have led to greater prevalence of apparent resistant hypertension (ARH), yet the long-term prognostic impact of ARH diagnosed according to these goals in the general population remains unknown. We assessed the prognostic impact of ARH according to contemporary BP goals in 9612 participants of the Atherosclerosis Risk in Communities (ARIC) study without previous cardiovascular disease. ARH, defined as BP above goal (traditional goal = 3 antihypertensive drug classes or any BP with >= 4 antihypertensive drug classes (one of which was required to be a diuretic) was compared with controlled hypertension (BP at goal with 1-3 antihypertensive drug classes). Cox regression models were adjusted for age, sex, race, study center, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, and diabetes. Using the traditional BP goal, 133 participants (3.8% of the treated) had ARH. If the more stringent BP goal was instead applied, 785 participants (22.6% of the treated) were reclassified from controlled hypertension to uncontrolled hypertension (n = 725) or to ARH (n = 60). Over a median follow-up time of 19 years, ARH was associated with increased risk for a composite end point (all-cause mortality, hospitalization for myocardial infarction, stroke, or heart failure) regardless of whether traditional (adjusted HR 1.50, 95% CI: 1.23-1.82) or more stringent (adjusted HR 1.43, 95% CI: 1.20-1.70) blood pressure goals were applied. We conclude that in patients free from cardiovascular disease, ARH predicted long-term risk regardless of whether traditional or more stringent BP criteria were applied. Funding Agencies|National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human ServicesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I]; Swedish Heart Association, Sweden; Swedish Society of Medicine, Sweden; Region Ostergotland, Sweden; NIH/NHLBIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL135008, R01HL143224, R01HL150342, R01HL148218, K24HL152008]

Henry A. Wallace challenged the bipartisan foreign policy of President Truman in 1948. The Progressive Citizens of America opposed Truman’s “get-tough policy” (the Truman Doctrine, loyalty investigations, Universal Military Training, and the Marshall Plan) and founded the Progressive Party. Other “liberals” formed Americans for Democratic Action and supported Truman, who claimed that the Progressive Party was a Soviet construction. Wallace refused to participate in segregated meetings during his campaign in the South and was violently attacked. He advocated the need for federal measures to prohibit segregation, discrimination, the poll tax, and lynching. Wallace was resoundingly defeated but proved right in the long run: military means could not solve social problems. Instead, it spread hatred of the United States in many countries. The 1948 election determined U.S. foreign policy for over 50 years, resulting in missed opportunities to improve housing, education, and social security at home, which still has repercussions today. JEL Classifications: N42, F50

Objective: To study risk in white-coat hypertension (WCH) by measurement of coronary artery calcium score (CACS), carotid--femoral pulse-wave velocity (PWV) and carotid plaques. Methods: Cross-sectional population-based cohort with randomized selection of participants from Linkoping, Sweden. An Omron m10-IT oscillometric device was used for clinic and home blood pressures (HBP) in the morning and evening for 1 week. Results: We recruited 5029 middle-aged and mainly defined WCH as SBP at least 140 mmHg and/or DBP at least 90 mmHg with HBP less than 135/85 mmHg. There were 2680 normotensive participants and 648 had WCH after exclusion of treated participants. More women (59.5%) than men (42.8%, P < 0.001) had WCH. We found higher prevalence of CACS greater than 100 compared with less than 100 (12.4 vs. 7.2%, P < 0.001), PWV (11.5 +/- 1.5 vs. 10.4 +/- 1.3 m/s, P < 0.001) and a higher prevalence of one or more carotid plaques (59.5 vs. 48%, P < 0.001) in participants with WCH than in normotension. Participants with WCH also had more dyslipidemia and higher glucose levels. Normotensive women scored lower on nervousness than women with WCH (P = 0.022). After matching of 639 participants with WCH to normotensive participants according to age, gender and systolic HBP the prevalence of a high CACS (12.1 vs. 8.6%, P = 0.003,) PWV (11.0 +/- 0.068 vs. 11.5 +/- 0.068 m/s, estimated marginal means +/- SE, P < 0.001 by ANOVA) but not more carotid plaques (59.5 vs. 55.6%, P = 0.23), remained in the participants with WCH compared with the matched normotensive participants. Conclusion: WCH is particularly common in middle-aged women, and it displays metabolic dysfunction and increased prevalence of arteriosclerotic manifestations in both genders. As markers of increased cardiovascular risk were present also after matching normotensive and WCH participants according to systolic HBP, age and gender, the presence of WCH signals an increased cardiovascular risk burden that is not fully explained by elevated BP levels at home. Funding Agencies|Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; FORSS, the Medical Research Council of Southeast Sweden

Background: People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation. Method: The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG. Results: There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 ( P = .16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment ( P < .001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG. Conclusion: Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.

OBJECTIVE Continuous glucose monitoring (CGM) reduces HbA1c and time spent in hypoglycemia in people with type 1 diabetes (T1D) treated with multiple daily insulin injections (MDI) when evaluated over shorter time periods. It is unclear to what extent CGM improves and helps to maintain glucose control, treatment satisfaction, diabetes distress, hypoglycemic concerns, and overall well-being over longer periods of time. RESEARCH DESIGN AND METHODS The GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in people with T1D treated with MDI. People completing the trial (n = 141) were invited to participate in the current SILVER extension study in which 107 patients continued CGM treatment over 1 year along with the support of a diabetes nurse every 3 months. RESULTS The primary end point of the change in HbA1c over 1.0–1.5 years of CGM use compared with previous self-monitoring of blood glucose during GOLD showed a decrease in HbA1c of 0.35% (95% CI 0.19–0.50, P < 0.001). Time spent in hypoglycemia CONCLUSIONS The SILVER study supports beneficial long-term effects from CGM on HbA1c, hypoglycemia, treatment satisfaction, well-being, and hypoglycemic confidence in people with T1D managed with MDI.

Background The relationship between blood pressure and mortality in type 2 diabetes (T2DM) is controversial, with concern for increased risk associated with excessively lowered blood pressure. Methods We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline blood pressure and all-cause mortality in 5852 patients with T2DM and a recent acute coronary syndrome (ACS) who participated in the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial. Risk of death was assessed in Cox models adjusted for age, sex, race, heart rate, BMI, smoking, diabetes duration, insulin use, HbA1c, eGFR, brain natriuretic peptide (BNP), urine albumin/creatinine ratio, treatment allocation and prior coronary revascularization. Results Although overall there was no significant association between systolic blood pressure (SBP) and mortality (hazard ratio per 10 mmHg lower SBP 1.05 (95% CI 0.99–1.12) P = 0.10), lower SBP was significantly associated with higher risk of death (hazard ratio per 10 mmHg lower SBP 1.13 (95% CI 1.04–1.22) P = 0.002) in 2325 patients with additional CVD (index ACS+ at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure). In 3527 patients with only the index ACS no significant association was observed (hazard ratio per 10 mmHg lower SBP 0.95 (0.86–1.04) P = 0.26; P for interaction 0.005). Conclusions The association between blood pressure and mortality was modified by additional CVD history in patients with type 2 diabetes and a recent coronary event. When blood pressures measured after an acute coronary event are used to assess the risk of death in patients with type 2 diabetes, the cardiovascular history needs to be taken into consideration. Trial registration ClinicalTrials.gov number NCT01147250, first posted June 22, 2010

We recruited 78 men and 94 women to investigate if the proportion of subjects with well-controlled home blood pressure levels could be increased when treatment was guided by smartphone-based telemonitoring. All patients were prescribed one to three antihypertensive drugs. The Accumbo smartphone telemonitoring application was downloaded to the Iphones of the participants and home blood pressure information was gathered from semi-automatic oscillometric blood pressure-recorders by Bluetooth. The study physician adjusted the medications based on home blood pressure for 3 months. home blood pressure was controlled (

Aims Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on ‘apparent resistant hypertension’ in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril–valsartan with valsartan. Methods and results In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n = 4795). ‘Apparent resistant hypertension’ was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. ‘Apparent mineralocorticoid receptor antagonist (MRA)-resistant’ hypertension was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril–valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6–19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7–14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05–1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril–valsartan vs. valsartan in patients with apparent resistant hypertension [−4.8 (−7.0 to −2.5) and 3.9 (−6.6 to −1.3) mmHg] and apparent MRA-resistant hypertension [−8.8 (−14.0 to −3.5) and −6.3 (−12.5 to −0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril–valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30–2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18–5.89). Conclusion Sacubitril–valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA. Clinical trial registration PARAGON-HF: ClinicalTrials.gov Identifier NCT01920711., Graphical Abstract Almost one in six patients with heart failure and preserved ejection fraction had apparent resistant hypertension in PARAGON-HF and this was associated with worse clinical outcomes; neprilysin inhibition reduced systolic blood pressure significantly in these patients.

In his third term, Roosevelt appointed Vice President Henry A. Wallace to Chair the Board of Economic Warfare. Conflicts soon arose with Secretaries Jessie Jones and Cordell Hull. An ailing Roosevelt replaced Wallace by Leo Crowley and adopted a bipartisan policy to win the war. He abandoned the New Deal, and left to Wallace to support trade unions, to protect the rights of Blacks in the South and of those working in defense industries in the North and to champion the interests of the common man. Roosevelt dropped Wallace from the ticket in 1944 to get southern support to run for a fourth term. As Secretary of Commerce in President Truman’s cabinet, Wallace advocated normalizing relations with the U.S.S.R. But like his father before him, he now represented a minority view in a government dominated by industrial, military, and financial interests. At the urging of Secretary of State Byrnes, President Truman dismissed Wallace in 1946. JEL Classification: F5.

In three successive generations, a Henry Wallace advocated interests of the agricultural Midwest: trust busting, natural resource conservation, application of science in agricultural, freer trade, and international comity. While characterized as a Midwest institution, the family’s success as Secretaries of Agriculture ultimately depended on presidential support. Henry C. Wallace failed to restore prosperity to farmers in the depression after World War I due to the opposition of President Harding. His son Henry A. Wallace succeeded in the Great Depression thanks to strong support of President Roosevelt. JEL Classifications: N13, Q15

Liraglutide is associated with blood pressure reduction in patients with type 2 diabetes. However, it is not known whether this blood pressure reduction can be predicted prior to treatment initiation, and to what extent it correlates with weight loss and with improved glycemic control during follow‐up. We analyzed data from a double‐blind, placebo‐controlled trial, in which 124 insulin‐treated patients with type 2 diabetes were randomized to liraglutide or placebo. We evaluated various baseline variables as potential predictors of systolic blood pressure (SBP) reduction, and evaluated whether changes in SBP correlated with weight loss and with improved glycemic control. A greater reduction in SBP among liraglutide‐treated patients was predicted by higher baseline values of SBP (P

Hemodynamic responses to exercise in the acute phase after moderate to severe stroke have remained poorly investigated. The aim of this randomized controlled study, in which 52 (32 women) patients with moderate to severe stroke were randomized to three weeks of 20 minutes in-bed cycle exercise 5 days per week or to usual care, was to explore the systolic blood pressure (SBP) response to exercise and to evaluate the impact of the intervention on the resting and post-test systolic and diastolic blood pressures and heart rate, and on the systolic blood pressure response to exercise. We found that resting SBP decreased from baseline to post-intervention in both the intervention group (147.7 +/- 18.1 mmHg to 125.3 +/- 17.1 mmHg, P < .001) and in the control group (147.8 +/- 23.7 mmHg to 131.4 +/- 14.8 mmHg, P < .001) without a significant difference between the groups (interaction P = .308). However, there was a significant difference (interaction P = .010) regarding how. SBP (change in SBP from pre-test to post-test) changed from baseline to post-intervention. In the intervention group, Delta SBP increased from -1.0 +/- 15.0 mmHg to 8.5 +/- 9.4 mmHg, P = .009, whereas in the control group, Delta SBP decreased from 7.1 + 10.9 mmHg to 4.5 + 11.8 mmHg, P = .395. We conclude that patients randomized to in-bed cycle exercise seemed to normalize their blood pressure response to exercise to a larger extent than patients in the control group. Funding Agencies|Henry and Ella Margareta Stahl Foundation, Norrkoping, Sweden; Medical Research Council of Southeast Sweden, Sweden; Research and Development Council, Local Health Care, Norrkoping, Sweden

Aim To identify responders to continuous glucose monitoring (CGM) in relation to reductions in HbA1c and percentage of time spent in hypoglycaemia after initiation of CGM for individuals with type 1 diabetes treated with multiple daily insulin injections. Materials and Methods We analysed data from 142 participants in the GOLD randomized clinical trial. We evaluated how many lowered their HbA1c by more than 0.4% (>4.7 mmol/mol) or decreased the time spent in hypoglycaemia over 24 hours by more than 20 or 30 minutes, and which baseline variables were associated with those improvements. Results Lower reduction of HbA1c was associated with greater reduction of hypoglycaemia (r = -0.52; P < .0001). During CGM, 47% of participants lowered their HbA1c values by more than 0.4% (>4.7 mmol/mol) than with self-measurement of blood glucose, and 47% decreased the time spent in hypoglycaemia by more than 20 minutes over 24 hours. Overall, 78% either reduced their HbA1c by more than 0.4% (>4.7 mmol/mol) or the time spent in hypoglycaemia by more than 20 minutes over 24 hours, but only 14% improved both. Higher HbA1c, a lower percentage of time at less than 3.0 or 3.9 mmol/L, a lower coefficient of variation (CV) and a higher percentage of time above 13.9 mmol/L (P = .016) were associated with greater HbA1c reduction during CGM. The variables associated with a greater reduction of time in hypoglycaemia were female sex, greater time with glucose levels at less than 3.0 mmol/L, higher CV, and higher hypoglycaemia confidence as evaluated by a hypoglycaemic confidence questionnaire. Conclusion The majority of people with type 1 diabetes managed by multiple daily insulin injections benefit from CGM; some experienced reduced HbA1c while others reduced the time spent in hypoglycaemia. These factors need to be considered by healthcare professionals and decision-makers for reimbursement and diabetes guidelines. Funding Agencies|NU Hospital Group, Trollhattan, Sweden; Dexcom, Inc.; Swedish government (Avtalet om Lakareutbildning och Medicinsk Forskning [Agreement for Medical Education and Research]); NU Hospital Group, Uddevalla, Sweden

Objective: Continuous Glucose Monitoring (CGM) reduces HbA1c and time spent in hypoglycemia in persons with type 1 diabetes treated with multiple daily insulin injections (MDI) when evaluated over shorter time periods. It is unclear to what extent CGM improves and helps to maintain glucose control, treatment satisfaction, diabetes distress, hypoglycemic concerns and overall well-being over longer periods of time Research design and methods: The GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in persons with type 1 diabetes treated with MDI. Persons completing the trial (n=141) were invited to participate in the current SILVER extension study in which 107 patients continued CGM treatment over 1 year along with the support of a diabetes nurse every 3 months. Results: The primary endpoint, change in HbA1c over 1.0-1.5 years CGM use compared with previous self-monitoring of blood glucose (SMBG) during GOLD, showed a decrease in HbA1c of 0.35% (95% CI 0.19-0.50), p Conclusions: The SILVER study supports beneficial long-term effects from CGM on HbA1c, hypoglycemia, treatment satisfaction, well-being and hypoglycemic confidence in persons with T1D managed with MDI.

Background/Introduction Abnormal thyroid hormone concentrations have been associated with adverse cardiovascular outcomes, but the relationship between thyroid dysfunction and specific heart failure phenotypes is less clear. Purpose To examine the association of thyroid dysfunction with the risk of incident HF in older adults without pre-existing HF. Methods We analyzed participants enrolled in the Atherosclerosis Risk in Communities (ARIC) study who attended the visit 5 examination (2011–2013). Participants with previous HF history, and participants treated with amiodarone, levothyroxine, and antithyroid medication were excluded. We used Cox regression models to assess the associations between serum thyroid indices (free thyroxine [FT4], total triiodothyronine [TT3], or thyroid stimulating hormone [TSH]) and incident adjudicated HF with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction. Continuous associations between TT3 and outcome were further assessed via Cox model using restricted cubic spline. Results Among 3349 participants (mean age 75±5 years, 56% women, 20% black), subclinical hypothyroidism was prevalent in 12% of participants and low T3 syndrome in 3%. Those with overt hypothyroidism ( Conclusions In a contemporary biracial cohort of older adults, serum T3 level was inversely associated with incident HFpEF hospitalization. T3 administration could be considered as a potential target in future clinical trials preventing HFpEF hospitalization. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Atherosclerosis Risk in Communities Study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute contracts

OBJECTIVE According to recent guidelines, individuals with type 1 diabetes should spend RESEARCH DESIGN AND METHODS In the GOLD randomized crossover trial, 161 individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) were randomized to continuous glucose monitoring (CGM) or conventional therapy with self-monitoring of blood glucose (SMBG) and evaluated over 16 months. We estimated the association between time spent in hypoglycemia and various mean glucose and HbA1c levels. RESULTS Time spent in hypoglycemia ( CONCLUSIONS Reaching current targets for time in hypoglycemia while at the same time reaching HbA1c targets is challenging for patients with type 1 diabetes treated with MDI both with CGM and SMBG monitoring. However, CGM is associated with considerably less time in hypoglycemia than SMBG at a broad range of HbA1c levels and is crucial for patients with MDI treatment if they are to have a chance to approach hypoglycemia targets.

Objective: According to recent guidelines, individuals with type 1 diabetes should spend less than 4.0% per day with glucose levels Research methods: In the GOLD randomised cross-over trial, 161 individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) were randomised to Continuous Glucose Monitoring (CGM) or conventional therapy with self-monitoring of blood glucose (SMBG) and evaluated over 16 months. We estimated the association between time spent in hypoglycaemia and various mean glucose and HbA1c levels. Results: Time spent in hypoglycaemia ( Conclusions: Reaching current targets for time in hypoglycaemia and at the same time HbA1c targets is challenging for type 1 diabetes patients treated with MDI both with CGM and SMBG monitoring. However, CGM is associated with considerably less time in hypoglycaemia than SMBG at a broad range of HbA1c levels and is crucial for patients with MDI treatment to have a chance to approach hypoglycaemia targets.

Continuous glucose monitoring (CGM) reduces HbAThe GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in people with T1D treated with MDI. People completing the trial (The primary end point of the change in HbAThe SILVER study supports beneficial long-term effects from CGM on HbA

The relationship between blood pressure and mortality in T2DM is controversial, with concern for increased risk associated with lower blood pressure. We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline systolic blood pressure (SBP) and mortality in 5852 patients with T2DM who, as required for entry to the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial, had a recent acute coronary syndrome (ACS). Risk of death was assessed in a Cox model that adjusted for age, sex, race, heart rate, BMI, smoking, diabetes duration, insulin use, HbA1c, eGFR, natriuretic peptide (BNP) and urine albumin/creatinine at baseline. Overall there was no significant association between SBP and risk of death (P=0.20), but in 2325 patients with additional CVD (index ACS + at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure) there was a significant association between lower SBP and higher risk of death (hazard ratio per 10 mmHg lower SBP 1.13; 95% CI 1.05 to 1.23) whereas in 3527 patients with only the index ACS no association was observed (hazard ratio per 10 mmHg lower SBP 0.95; 95% CI 0.86 to 1.04, P for interaction Disclosure M.O. Wijkman: None. B. Claggett: None. R. Diaz: None. H.C. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Kowa Pharmaceuticals America, Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Sanofi. L. Kober: Speaker’s Bureau; Self; AstraZeneca, Novartis AG. Other Relationship; Self; AstraZeneca. E. Lewis: Consultant; Self; Novartis Pharmaceuticals Corporation. Research Support; Self; Amgen, Novartis Pharmaceuticals Corporation, Theracos, Inc. A.P. Maggioni: None. E. Wolsk: None. D. Aguilar: None. R. Bentley-Lewis: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. J.L. Probstfield: None. M.C. Riddle: Consultant; Self; ADOCIA, Dance Biopharm Holdings, Inc., GlaxoSmithKline plc., Sanofi US, Theracos, Inc. Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. J. Tardif: Research Support; Self; Esperion Therapeutics, Inc., Ionis Pharmaceuticals, Inc., REGENXBIO Inc., Sanofi, Servier. Other Relationship; Self; Amarin Corporation, AstraZeneca, DalCor Pharmaceuticals. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. M.A. Pfeffer: Consultant; Self; AstraZeneca, CinCor, Correvio, Corvidia, DalCor Pharmaceuticals, GlaxoSmithKline plc., Innovative Science, Jazz Pharmaceuticals, MyoKardia, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., PharmaScience, Sanofi US, Servier, Takeda Development Center Americas, Inc. Research Support; Self; Novartis Pharmaceuticals Corporation. Funding Sanofi (NCT01147250)

We assessed the relative contributions of N-terminal pro-B-type natriuretic peptide (NTBNP) and high sensitivity cardiac troponin (hsTnT) to the prediction of death and cardiovascular (CV) events in 5597 (with complete data) of 8561 patients with type 2 diabetes (T2DM) and CV disease (CVD) and/or chronic kidney disease (CKD) enrolled in the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE). We analysed Harrell’s C-statistics (Cs) to estimate Cox model performance to predict death (n= 473) and a CV composite outcome (CVCO: CV death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke or heart failure hospitalization, n= 1129) after a median follow-up of 2.6 years, using a base model (BM) of 19 clinical baseline variables. The Cs for predicting death in the BM (0.724) was augmented by adding hsTnT (0.744, p= 0.002) which was further improved by NTBNP (0.779, p Disclosure M.V.B. Malachias: Speaker’s Bureau; Self; Biolab Sanus Farmaceutica, Libbs Farmaceutica. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. B. Claggett: None. M.O. Wijkman: None. R. Bentley-Lewis: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. P.C. Brunel: Consultant; Self; Novartis AG. N. Chaturvedi: Consultant; Self; AstraZeneca. A.S. Desai: Consultant; Self; Abbott, Alnylam Pharmaceuticals, AstraZeneca, Biofourmis, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Scientific, DalCor Pharmaceuticals, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Relypsa, Inc. Research Support; Self; Alnylam Pharmaceuticals, AstraZeneca, Novartis Pharmaceuticals Corporation. S.M. Haffner: None. H.D. Parving: None. M.F. Prescott: Employee; Self; Novartis Pharmaceuticals Corporation. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. D. de Zeeuw: Advisory Panel; Self; AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. M.A. Pfeffer: Consultant; Self; AstraZeneca, CinCor, Correvio, Corvidia, DalCor Pharmaceuticals, GlaxoSmithKline plc., Innovative Science, Jazz Pharmaceuticals, MyoKardia, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., PharmaScience, Sanofi US, Servier, Takeda Development Center Americas, Inc. Research Support; Self; Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals (NCT00549757)

CGM reduces A1c and time in hypoglycemia in persons with T1D treated with MDI evaluated over short time periods. It’s unclear to what extent CGM improves glucose control, treatment satisfaction, hypoglycemia fear and diabetes-related QoL long term. The GOLD trial was a 16 month randomized crossover trial of CGM use in persons with T1D treated with MDI. The SILVER study is an extension in which patients continued CGM use (DexcomG4/G5) for 1 year with clinical visits every 3 months. The primary endpoint, A1c change during long-term CGM use compared with SMBG during GOLD (from end of SMBG in GOLD until end of SILVER study/1.0-1.5 years), showed decreased A1c of 0.35% (95% CI 0.19-0.50), p The SILVER study supports beneficial long-term effects by CGM use on A1c, TIR, hypoglycemia, treatment satisfaction, wellbeing, hypoglycemia confidence and diabetes distress in persons with T1D treated with MDI. Disclosure M. Lind: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Research Support; Self; Dexcom, Inc., Novo Nordisk Inc. A.F. Olafsdottir: None. I.B. Hirsch: Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care. Research Support; Self; Medtronic, Omnipod. J. Bolinder: Advisory Panel; Self; Abbott. Consultant; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca. S. Dahlqvist: None. A. Pivodic: None. J. Hellman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. M.O. Wijkman: None. E. Schwarcz: Advisory Panel; Self; Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc. H. Albrektsson: None. T. Heise: Advisory Panel; Self; Mylan, Novo Nordisk A/S. Research Support; Self; ADOCIA, Aerami, Becton, Dickinson and Company, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Merck KGaA, Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. W. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Roche Diabetes Care. Consultant; Self; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Onduo, Sanofi US, Xeris Pharmaceuticals, Inc. Funding Dexcom, Inc.

Objective To investigate the effects of in-bed cycle exercise in addition to usual care in patients with acute stroke, National Institutes of Health Stroke Scale (NIHSS) 7-42, regarding walking ability, functional outcomes, and inpatient care days. Design Randomized controlled trial. Setting Hospital care. Participants Patients (N=56) with stroke NIHSS 7-42 were recruited 24-48 hours after stroke onset from 2 stroke units in Sweden. Interventions Both groups received usual care. The intervention group also received 20 minutes bed cycling 5 days per week with a maximum of 15 sessions. Main Outcome Measures The primary outcome was median change in walking ability measured with the 6-minute walk test (6MWT). Secondary outcome measures included the median change in modified Rankin Scale (mRS), Barthel Index (BI) for activities of daily living, and inpatient care days. Measurements were performed at baseline, post intervention (3 weeks), and at 3-month follow-up. Results There was no significant difference in change of walking ability (6MWT) from baseline to follow-up between the intervention and control groups (median, 105m [interquartile range [IQR, 220m] vs 30m [IQR, 118m], respectively, P=.147, d=0.401). There were no significant differences between groups regarding mRS, BI, or inpatient care days. Patients with less serious stroke (NIHSS 7-12) seemed to benefit from the intervention. Conclusion Although this study may have been underpowered, patients with stroke NIHSS 7-42 did not benefit from in-bed cycle exercise in addition to usual care after acute stroke. A larger study is needed to confirm our results.

OBJECTIVE According to recent guidelines, individuals with type 1 diabetes should spend

Aims: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. Methods: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight amp;lt; 25 kg/m(2), overweight 25-29 kg/m(2), and obesity amp;gt;= 30 kg/m(2) ). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. Results: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/e (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p amp;lt; 0.05 vs. p amp;lt;0.05). Corresponding results in the control group were 58% (6%) vs. -22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p amp;lt;0.05 vs. p amp;lt;0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n =187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n =179) (p amp;lt;0.05). Conclusion: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons. Funding Agencies|FORSS; Research Council of Southeastern Sweden; Swedish Heart-Lung foundation; King Gustaf V and Queen Victoria Freemason Foundation, Sweden

Our aim was to analyze the predictive value of toe brachial index (TBI) as a risk marker for future major adverse cardiovascular events (MACE) and all-cause mortality in patients with type 2 diabetes (T2D).TBI was measured in 741 patients with T2D in 2005-2008. Conventional risk factors for vascular disease as well as non-invasive measurements such as pulse-wave velocity (PWV) and intima-media thickness (IMT) of the carotid arteries were estimated. MACE was defined as cardiovascular death or hospitalization for non fatal myocardial infarction or non fatal stroke. Patients were followed for incidence of MACE using the national Swedish Cause of Death Registry and the Inpatient Register.During the follow-up for a period of 9 years MACE occurred in 97 patients and 85 patients died. TBI tertile, 1 versus 3, was significantly related to MACE (HR 2.67, 95%CI 1.60-4.50; p 0.001) and to all-cause mortality (HR 1.98, 95%CI 1.16-3.83; p = 0.01). TBI tertile 1 as compared to TBI tertile 3 predicted MACE, but not all-cause mortality, independently of age, sex, diabetes duration and treatment, antihypertensive treatment, previous cardiovascular diseases, office systolic blood pressure, HbA1c, LDL cholesterol, estimated glomerular filtration rate, body mass index, current smoking PWV, IMT and carotid plaque presence (HR 3.39, 95%CI 1.53-7.51; p = 0.003 and HR 1.81, 95%CI 0.87-3.76; p = 0.1, respectively).Low TBI predicts an increased risk for MACE independently of arterial stiffness in patients with type 2 diabetes.Clinical Trials.gov number NCT01049737. Registered January 14, 2010.

The aim was to evaluate the predictive value of aortic pulse wave velocity (aPWV) on incident cardiovascular events in patients with type 2 diabetes without previous cardiovascular disease who were treated in primary care, after adjustment for traditional risk factors.We measured aPWV in 627 patients who participated in the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes-a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) and who did not have previously known myocardial infarction or stroke. The outcome variable was a composite endpoint consisting of cardiovascular mortality, hospitalization for myocardial infarction and hospitalization for stroke.During a median follow-up time of almost eight years, the unadjusted HR per each increment of aPWV by 1m/s was 1.239 (95% CI 1.114-1.379, P0.001) for the primary endpoint. Following adjustments for age, sex, diabetes duration, office systolic blood pressure, resting heart rate, total cholesterol, HbA1c, estimated glomerular filtration rate and smoking status, the adjusted hazard ratio was 1.142 (95% CI 1.003-1.301, P=0.044).In primary preventive patients with type 2 diabetes treated in primary care, aPWV predicted a composite outcome of incident cardiovascular events independently of diabetes-specific and traditional risk factors.

Background: To evaluate the effects of continuous glucose monitoring (CGM) on nocturnal and daytime hypoglycemia in persons with type 1 diabetes treated with multiple daily insulin injections (MDI); we also evaluated factors related to differences in hypoglycemia confidence in this population. Methods: Evaluations were performed from the GOLD randomized trial, an open-label multicenter crossover randomized clinical trial (n = 161) over 69 weeks comparing CGM to self-measurement of blood glucose (SMBG) in persons with type 1 diabetes treated with MDI. Masked CGM and the hypoglycemia confidence questionnaire were used for evaluations. Results: Time with nocturnal hypoglycemia, glucose levels

Following popular protests at home and the fall of the government, Ukraine reversed course and joined Georgia and Moldova in signing Association Agreements in June 2014. This article has two main aims. First, using a gravity model of trade, it estimates the effects of deep and shallow free trade agreements for the EaP (Eastern Partnership) states with Russia and the EU respectively. Second, by relating the outcomes of the first estimation to the quality of institutions, proxied with the level of democracy and the level of corruption in the selected countries, the paper estimates the effect on exports of changes in the quality of institutions. The main results show that the EaP countries gain significantly from free trade agreements with the EU but little if anything from free trade agreements with Russia, and that improvements in the quality of institutions in EaP countries have played an important role in fostering exports.

The prevalence of an exaggerated exercise blood pressure (BP) response is unknown in patients with subacute stroke, and it is not known whether an aerobic exercise program modulates this response. The authors randomized 53 patients (27 women) with subacute stroke to 12 weeks of twice-weekly aerobic exercise (n = 29) or to usual care without scheduled physical exercise (n = 24). At baseline, 66% of the patients exhibited an exaggerated exercise BP response (peak systolic BP ≥210 mm Hg in men and ≥190 mm Hg in women) during a symptom-limited ergometer exercise test. At follow-up, patients who had been randomized to the exercise program achieved higher peak work rate, but peak systolic BP remained unaltered. Among patients with a recent stroke, it was common to have an exaggerated systolic BP response during exercise. This response was not altered by participation in a 12-week program of aerobic exercise.

Under what conditions can the European Neighbourhood Policy (ENP) achieve one of the objectives of the European Union (EU): to resolve conflicts in its neighbourhood? In the spirit of Montesquieu and Monnet, the basic hypothesis of the EU is that closer economic integration helps resolve political conflicts and vice versa, creating a virtuous circle of prosperity and detente. The EU has a strong self-interest in resolving conflicts in its neighbourhood since their consequences spill over into the EU itself through refugee flows and trans-border criminal activities. The paper identifies factors important for the neighbourhood countries to succeed: access to active facilitators of compromise, a well-functioning market economy, strong common institutions to realise potential intra-regional free trade, the prospect of accession to the EU and the absence of third parties to the conflicts. However, characteristic of the key conflicts in the European Neighbourhood is that few of the parties are prospective members of the EU and that a third party outside the Partnership is involved in major conflicts. To succeed in conflict resolution, the EU must, therefore, provide these parties significantly stronger arbitration, more technical and financial resources and stronger institutions anchoring the partner country to the EU. This applies to conflicts involving partners in the Eastern Partnership as well as in the Mediterranean Partnership.

The impact of beta‐blockers (BB) treatment on stroke outcome is unclear. We used data from a prospective national stroke registry to assess the associations between use of BB and poor outcome 3 months after stroke. Using the National Acute Stroke Israeli (NASIS) registry, we identified 1126 patients with ischemic stroke and intracerebral hemorrhage with pre‐stroke hypertension treatment, who were followed for 3‐months. Functional outcome and mortality at 3‐month were compared by use of BB, adjusting for demographics and clinical factors. Pre‐stroke use of BB was reported by 615 (54.6%) patients. Users of BB showed higher rates of atrial fibrillation, heart disease, statin use, cancer, and severe stroke. Adjusted odds‐ratios (ORs, 95% CI) for BB users compared with non‐users 3 months after stroke were 0.86 (0.49‐1.52) for mortality and 1.07 (0.76‐1.50) for Barthel Index ≤60. In conclusion, treatment with BB is not associated with 3‐month poor outcome in hypertensive patients.

Background: In patients with diabetes, high blood pressure is an established risk factor for cardiovascular disease. The aim of this thesis was to explore the associations between blood pressure levels measured with different techniques and during different circumstances, and the degree of cardiovascular organ damage and subsequent prognosis in patients with diabetes. Methods: We analysed baseline data from patients with type 2 diabetes who participated in the observational cohort study CARDIPP (Cardiovascular Risk factors in Patients with Diabetes – a Prospective study in Primary care), and longitudinal data from patients registered in the Swedish national quality registry RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive care Admissions). Patients in CARDIPP underwent nurse-recorded, 24-hour ambulatory and non-invasive central blood pressure measurements. Patients in RIKS-HIA had their systolic blood pressure measured upon hospitalisation for acute chest pain. Results: In CARDIPP, nearly one in three patients with office normotension (

This study was designed to evaluate the prevalence of masked nocturnal hypertension (MNHT) and its impact on arterial stiffness and central blood pressure in patients with type 2 diabetes.Middle-aged patients (n = 414) with type 2 diabetes underwent clinic and ambulatory BP measurements and applanation tonometry.MNHT (clinic BP130/80 mmHg and night-time BPor = 120/70 mmHg) was found in 7.2% of patients (n = 30). Compared with patients with both clinical and nocturnal normotension (n = 70), patients with MNHT had higher aortic pulse wave velocity (PWV) (10.2 +/- 1.8 m/s vs 9.4 +/- 1.7 m/s; p = 0.03) and higher central BP (117.6 +/- 13.9/74.0 +/- 9.1 mmHg vs 110.4 +/- 16.4/69.7 +/- 9.6 mmHg, p = 0.04). In patients with clinical normotension, night-time systolic BP correlated significantly with PWV.Thirty per cent of patients with clinical normotension had nocturnal hypertension. This was accompanied by increased arterial stiffness and higher central BP. We conclude that in clinically normotensive patients with type 2 diabetes, ambulatory BP measurement may help clinicians to identify patients with increased cardiovascular risk.

Background: Low levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D-3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes. Methods: The main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the "Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care" study. Patients were 55-66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry. Results: Levels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p greater than 0.9). Conclusions: Serum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV. Funding Agencies|Medical Research Council of Southeast Sweden; Futurum; King Gustaf V and Queen Victoria Freemason Foundation; GE Healthcare; Swedish Heart-Lung Foundation; Swedish Research Council [12661]; County Council of Ostergotland; Linkoping University, Department of Medical and Health Sciences

Using a panel gravity model of trade for the period 1995–2010, this paper estimates the potential for increased intra-regional trade among 10 countries of the southern and eastern Mediterranean coast. It examines how closer integration through the EU’s revised neighborhood policy can encourage democratisation and conflict resolution. The main results indicate that while the gains realized to date from regional integration have been small, significant potential gains from deep integration exist. The paper proposes that the EU starts by negotiating deep and comprehensive free trade agreements with Egypt, Israel and Jordan provided these countries also negotiate them with each other. Inmaculada Martínez-Zarzoso gratefully acknowledges the financial support received from the research project (ECO2010-15863) granted by the Spanish Ministry of Science and Innovation.

Excessive concentration increases national risk in an uncertain world. This paper views economic and political diversification as an essential aspect of national risk management aimed at promoting efficiency, growth, and welfare. The paper first presents economic and political diversification side by side in a cross-country framework and discusses how they interact and encourage more stable long-run economic growth. Thereafter, the paper considers Iceland as a case study of the intertwined effects of insufficient economic and insufficient political diversification. Dominated for decades by the fishing industry, the Icelandic economy is more diversified than before following the financial crisis of 2008 with tourism now generating more foreign exchange than fisheries. The paper ends with some general policy conclusions.

In a major setback for the EU, only two of four Eastern Partnership countries actually initialed Association Agreements at the Vilnius Summit in November 2013. This paper asks what went wrong and what can be done about it. Using a gravity model to estimate the effects of deep and shallow free trade agreements for the Eastern Partnership states with Russia and the EU, the paper shows that the Eastern Partnership countries, including Ukraine, by far the largest in the group, gain significantly from free trade agreements with the EU, but gain little if anything from free trade agreements with Russia.

Aim To explore risk factors for peripheral arterial disease (PAD) as well as the association between toe blood pressure and subclinical and clinical central vascular disease in patients with type 2 diabetes. Method Toe brachial index (TBI) was cross-sectionally analyzed in 742 middle-aged (54–66 years) patients with type 2 diabetes as well as non-diabetic controls and related to other vascular measures (e.g. carotid intima media thickness (IMT), presence of carotid plaque, central arterial stiffness and left ventricular mass index) and previous cardiovascular events. Results A TBI ≤ 0.7 was seen in 22% of the patients but only one patient had severe TBI reduction (TBI ≤ 0.3). The corresponding figures in the controls were 13% and 0%, respectively. Mean TBI was significantly lower in patients with type 2 diabetes than in controls (0.81 ± 0.14 vs. 0.87 ± 0.15, p Funding Agencies|Medical Research Council of Southeast Sweden||King Gustav V and Queen Victorias foundation||Center for Medical Image Science and Visualization (CMIV)||Linkoping University||County Council of Ostergotland||GE Healthcare||Swedish Heart-Lung Foundation||Swedish Research Council|12661|Diabetes Research Center