A Randomized Clinical Trial of Attempted Suicide Short Intervention Program versus Crisis Counseling in Preventing Repeat Suicide Attempts: A Two-Year Follow-Up Study.

INTRODUCTION: The Attempted Suicide Short Intervention Program (ASSIP) is a brief psychotherapeutic intervention, and a pivotal study found it to be remarkably effective in reducing repeat suicide attempts. OBJECTIVE: To compare the effectiveness of ASSIP to crisis counseling (CC) in a randomized clinical trial (ISRCTN13464512). METHODS: Adult patients receiving treatment for a suicide attempt in a Helsinki City general hospital emergency room in 2016-2017 were eligible to participate. We excluded psychotic or likely non-adherent substance-abusing or substance-dependent patients. Eligible patients (n = 239) were randomly allocated to one of two interventions. (a) ASSIP comprised three visits, including a videotaped first visit, a case formulation, and an individualized safety plan, plus letters from the therapist every 3 months for 1 year, and then, every 6 months for the next year. (b) CC typically involved 2-5 (median 3) face-to-face individual sessions. In addition, all participants received their usual treatment. One and 2 years after baseline, information related to participants' suicidal thoughts and attempts, and psychiatric treatment received was collected via telephone and from medical and psychiatric records. RESULTS: Among randomized patients, two-thirds initiated either ASSIP (n = 89) or CC (n = 72), with 73 (82%) completing ASSIP and 58 (81%) CC. The proportion of patients who attempted suicide during the 2-year follow-up did not differ significantly between ASSIP and CC (29.2% [26/89] vs. 35.2% [25/71], OR 0.755 [95% Cl 0.379-1.504]). CONCLUSIONS: We found no difference in the effectiveness of the two brief interventions to prevent repeat suicide attempts.

Association of education and feedback on hypertension management with risk for stroke and cardiovascular disease.

PURPOSE: Education and feedback on hypertension management has been associated with improved hypertension control. This study aimed to assess the effectiveness of such interventions to reduce the risk of stroke and cardiovascular events. MATERIALS AND METHODS: Individuals ≥18 years with a blood pressure (BP) recording in Västerbotten or Södermanland County during the study period 2001 to 2009 were included in 108 serial cohort studies, each with 24 months follow-up. The primary outcome was risk of first-ever stroke in Västerbotten County (intervention) compared with Södermanland County (control). Secondary outcomes were first-ever major adverse cardiovascular event (MACE), myocardial infarction, and heart failure, as well as all-cause and cardiovascular mortality. All outcomes were analysed using time-to-event data included in a Cox proportional hazards model adjusted for age, sex, hypertension, diabetes, coronary artery disease, atrial fibrillation, systolic BP at inclusion, marital status, and disposable income. RESULTS: A total of 121 365 individuals (mean [SD] age at inclusion 61.7 [16.3] years; 59.9% female; mean inclusion BP 142.3/82.6 mmHg) in the intervention county were compared to 131 924 individuals (63.6 [16.2] years; 61.2% female; 144.1/81.1 mmHg) in the control county. A first-ever stroke occurred in 2 823 (2.3%) individuals in the intervention county, and 3 584 (2.7%) individuals in the control county (adjusted hazard ratio 0.96, 95% CI 0.90 to 1.03). No differences were observed for MACE, myocardial infarction or heart failure, whereas all-cause mortality (HR 0.91, 95% CI 0.87 to 0.95) and cardiovascular mortality (HR 0.91, 95% CI 0.85 to 0.98) were lower in the intervention county. CONCLUSIONS: This study does not support an association between education and feedback on hypertension management to primary care physicians and the risk for stroke or cardiovascular outcomes. The observed differences for mortality outcomes should be interpreted with caution.

What is important for the sustained implementation of evidence-based brief psychotherapy interventions in psychiatric care? A quantitative evaluation of a real-world programme.

PURPOSE: Behavioural activation and motivational interviewing, both evidence-based treatments (EBTs), were implemented in secondary psychiatric care. This longitudinal evaluation of a real-world programme focused on the penetration of EBT adoption and its associations with therapist-related and perceived intervention-related variables. The implementation plan was also compared to sub-processes of Normalization Process Theory. MATERIAL AND METHODS: Six participating units employed 72 therapists regularly and they comprise the target group. Due to staff turnover, a total of 84 therapists were trained stepwise. Three survey points (q1, q2, q3) were set for a four-year cycle beginning a year after the initial training and completed 4-5 months after closing patient recruitment. The implementation plan included two workshop days, one for each EBT, and subsequent case consultation groups and other more general strategies. RESULTS: Fifty-seven (68%) of programme-trained therapists responded to one or more of three questionnaires. The self-reported penetration covers about a third of the target group a few months after the completion of the programme. Therapists' favourable perceptions of the EBTs regarding relative advantage, compatibility and complexity were associated with their sustained adoption. Therapists' background factors (e.g. work experience) and positive adoption intention at q1 did not predict the actual adoption of the EBTs at q3. No specific sustainment strategies were included in the implementation plan. CONCLUSION: Brief but multi-faceted training with subsequent case consultations promoted the adoption of EBTs in a real-world setting. Adding specific sustainment strategies to the implementation plan is proposed to ensure the long-term survival of the implementation outcomes.

Behavioral activation versus treatment as usual in naturalistic sample of psychiatric patients with depressive symptoms: a benchmark controlled trial.

BACKGROUND: More systematic use of evidence-based brief therapies is needed in the treatment of depression within psychiatric care. The aim of this study was to explore the impact of behavioral activation therapy (BA) for patients with depressive symptoms in a routine clinical setting of secondary psychiatric care. METHODS: The BA-treated intervention group (n = 242) comprised patients with depressive symptoms (Beck Depression Inventory (BDI) score ≥ 17 at baseline). The control group (n = 205) patients received treatment as usual in the same catchment area. The groups were matched at baseline using BDI and Alcohol Use Disorders Identification Test scores and inpatient/outpatient status. The groups were compared at 6-, 12- and 24-month follow-up points on functional outcome (Global Assessment of Functioning scale), service use, dropout and deaths. The Montgomery-Åsberg Depression Rating Scale was used to assess depressive symptoms in the intervention group. RESULTS: The estimated difference in GAF score between intervention and control group patients was significant at 12- and 24-months follow-up points in favor of intervention group (GAF score difference 4.85 points, p = 0.006 and 5.71 points, p = 0.005, respectively; estimate for patient group 2.26, p = 0.036). The rates of dropout, mortality and service use were similar between the groups. Among the intervention group patients, the estimated improvement in MADRS score compared to baseline was statistically significant throughout the follow-up (p < 0.001 at all follow-up points). CONCLUSIONS: The systematic use of BA among secondary psychiatric care depressive patients provides encouraging results despite the patients had various comorbid non-psychotic disorders. TRIAL REGISTRATION: ClinicalTrials.gov , Identifier NCT02520271, Release Date: 06/27/2015, retrospectively registered.

The relationship of electrocardiographic left ventricular hypertrophy to decreased serum potassium.

BACKGROUND: Low serum potassium (K) is associated with increased blood pressure, impaired cardiac function and renal dysfunction. Although lower serum K is associated with cardiac hypertrophy in animal models, the relationship of low serum K to the presence and severity of electrocardiographic left ventricular hypertrophy (LVH) is unclear. METHODS: Baseline and yearly Cornell product LVH levels were examined in relation to low serum K (serum K ≤ 3.90 mEq/l, the lowest quartile of baseline K levels) in 8586 patients with baseline K levels. Patients were randomized to losartan-vs atenolol-based treatment and additional hydrochlorothiazide (HCTZ) therapy as needed. RESULTS: After adjusting for age, sex, race, prior antihypertensive treatment, losartan vs atenolol therapy, HCTZ use, baseline diastolic and systolic pressure, body mass index, serum creatinine and urine albumin/creatinine ratio, baseline serum K ≤ 3.90 was associated with significantly higher mean baseline Cornell product LVH (2898 vs 2801 mm•ms, p = 0.001) and a 24% higher risk of Cornell product LVH > 2440 mm•ms at baseline (OR 1.24, 95% CI 1.11-1.38, p < 0.001). After also adjusting for baseline Cornell product and changes in diastolic and systolic pressure between baseline and each year of measurement, in-treatment serum K ≤ 3.90 determined yearly was associated with significantly higher mean Cornell product LVH at years 1-3 and with statistically significant 16-32% increased risks of LVH by Cornell product at years 1-4. CONCLUSIONS: A low serum K is independently associated with a greater likelihood and severity of Cornell product LVH during antihypertensive therapy.

Impact of Comorbid Alcohol Use Disorder on Health-Related Quality of Life Among Patients With Depressive Symptoms.

Background and Aim: In psychiatric clinical practice, comorbidity of depression and alcohol use disorder (AUD) is common. Both disorders have a negative impact on health-related quality of life (HRQoL) in general population. However, research on the impact of comorbid AUD on HRQoL among clinically depressed patients is limited. The purpose of this study was to explore the impact of a psychosocial treatment intervention on HRQoL for depressive patients in specialized psychiatric care with a special focus on the impact of AUD on HRQoL. Material and Methods: Subjects were 242 patients of the Ostrobothnia Depression Study (ClinicalTrials.gov Identifier NCT02520271). Patients referred to specialized psychiatric care who scored at least 17 points on the Beck Depression Inventory at baseline and who had no psychotic disorders were included in the ODS. The treatment intervention in ODS comprised behavioral activation for all but began with motivational interviewing for those with AUD. HRQoL was assessed regularly during 24-month follow-up by the 15D instrument. In the present study, HRQoL of ODS patients with or without AUD was compared and the factors explaining 15D score analyzed with a linear mixed model. In order to specify the impact of clinical depression on HRQoL during the early phase of treatment intervention, a general population sample of the Finnish Health 2011 Survey was used as an additional reference group. Results: HRQoL improved among all ODS study sample patients regardless of comorbid AUD during the first year of follow-up. During 12-24 months of follow-up the difference between groups was seen as HRQoL continued to improve only among the non-AUD patients. A combination of male gender, anxiety disorder, and AUD was associated with the poorest HRQoL in this sample. In combined sample analyses with the reference group, clinical depression had an impact on HRQoL in short-term follow-up regardless of the treatment intervention. Conclusions: This study suggests that, in terms of improvement in HRQoL, the heterogenous group of depressive patients in specialized psychiatric care can be successfully treated with behavioral activation in combination with motivational interviewing for those with AUD. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02520271. Ostrobothnia Depression Study (ODS). A Naturalistic Follow-up Study on Depression and Related Substance Use Disorders. (2015). Available online at: https://clinicaltrials.gov/ct2/show/NCT02520271.

A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Hypertension cannot always be adequately controlled with available drugs. We investigated the blood-pressure-lowering effects of the new vasodilatory, selective endothelin type A antagonist, darusentan, in patients with treatment-resistant hypertension. METHODS: This randomised, double-blind study was undertaken in 117 sites in North and South America, Europe, New Zealand, and Australia. 379 patients with systolic blood pressure of 140 mm Hg or more (>/=130 mm Hg if patient had diabetes or chronic kidney disease) who were receiving at least three blood-pressure-lowering drugs, including a diuretic, at full or maximum tolerated doses were randomly assigned to 14 weeks' treatment with placebo (n=132) or darusentan 50 mg (n=81), 100 mg (n=81), or 300 mg (n=85) taken once daily. Randomisation was made centrally via an automated telephone system, and patients and all investigators were masked to treatment assignments. The primary endpoints were changes in sitting systolic and diastolic blood pressures. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00330369. FINDINGS: All randomly assigned participants were analysed. The mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg (SD 14/8) with placebo, 17/10 mm Hg (15/9) with darusentan 50 mg, 18/10 mm Hg (16/9) with darusentan 100 mg, and 18/11 mm Hg (18/10) with darusentan 300 mg (p<0.0001 for all effects). The main adverse effects were related to fluid accumulation. Oedema or fluid retention occurred in 67 (27%) patients given darusentan compared with 19 (14%) given placebo. One patient in the placebo group died (sudden cardiac death), and five patients in the three darusentan dose groups combined had cardiac-related serious adverse events. INTERPRETATION: Darusentan provides additional reduction in blood pressure in patients who have not attained their treatment goals with three or more antihypertensive drugs. As with other vasodilatory drugs, fluid management with effective diuretic therapy might be needed. FUNDING: Gilead Sciences.

Importance of congruence between communicating and executing implementation programmes: a qualitative study of focus group interviews.

BACKGROUND: The Ostrobothnia Depression Programme (ODP) in Finland was intended to implement two evidence-based brief psychotherapy interventions, namely motivational interview and behavioural activation, in several regional psychiatric teams. A simultaneous effectiveness study was conducted. Considerable tension was encountered between these two arms, causing resistance to change. We conducted a qualitative case study to better understand this tension and to discuss how managerial and executive practices may ensure the successful running of a hybrid design programme. METHODS: We conducted focus group interviews to evaluate the phases of preparation and practical execution of the ODP from the perspectives of management and the programme executives. To gather the data, we applied the revised Socratic approach for health technology assessment and focus group interviews. We analysed the data deductively according to the Normalization Process Theory. RESULTS: We identified two main critical issues: (1) The ODP programme plan ignored the team leaders' crucial role in influencing the implementation climate and mobilizing organizational strategies. The ODP had a simplistic top-down design with minimal and delayed collaboration with its target groups in the preparation phase. (2) Incongruence occurred between what the project group had explicitly communicated about being the spearhead of the ODP and what they then actually enacted. These two issues caused tension between the implementation efforts and the effectiveness study as well as resistance to change among the staff. CONCLUSION: Early, open collaboration with all prospective stakeholders towards a shared understanding about the programme is the first action the programme administrators should take. Agreement on goals and the means to achieve them would lower tension between the two arms of a hybrid design programme, thereby reducing resistance to change. Congruence between the goals communicated and the actual managerial and executive actions is of paramount importance in getting the programme recipients on board.

Association of Physician Education and Feedback on Hypertension Management With Patient Blood Pressure and Hypertension Control.

Importance: Elevated systolic blood pressure (SBP) is the most important risk factor for premature death worldwide. However, hypertension detection and control rates continue to be suboptimal. Objective: To assess the association of education and feedback to primary care physicians with population-level SBP and hypertension control rates. Design, Setting, and Participants: This pooled series of 108 population-based cohort studies involving 283 079 patients used data from primary care centers in 2 counties (Västerbotten and Södermanland) in Sweden from 2001 to 2009. Participants were individuals aged 18 years or older who had their blood pressure (BP) measured and recorded in either county during the intervention period. All analyses were performed in February 2019. Exposures: An intervention comprising education and feedback for primary care physicians in Västerbotten County (intervention group) compared with usual care in Södermanland County (control group). Main Outcomes and Measures: Difference in mean SBP levels between counties and likelihood of hypertension control in the intervention county compared with the control county during 24 months of follow-up. Results: A total of 136 541 unique individuals (mean [SD] age at inclusion, 64.6 [16.1] years; 57.0% female; mean inclusion BP, 142/82 mm Hg) in the intervention county were compared with 146 538 individuals (mean [SD] age at inclusion, 65.7 [15.9] years; 58.3% female; mean inclusion BP, 144/80 mm Hg) in the control county. Mean SBP difference between counties during follow-up, adjusted for inclusion BP and other covariates, was 1.1 mm Hg (95% CI, 1.0-1.1 mm Hg). Hypertension control improved by 8.4 percentage points, and control was achieved in 37.8% of participants in the intervention county compared with 29.4% in the control county (adjusted odds ratio, 1.30; 95% CI, 1.29-1.31). Differences between counties increased during the intervention period and were more pronounced in participants with higher SBP at inclusion. Results were consistent across all subgroups. Conclusions and Relevance: This study suggests that SBP levels and hypertension control rates in a county population may be improved by educational approaches directed at physicians and other health care workers. Similar strategies may be adopted to reinforce the implementation of clinical practice guidelines for hypertension management.

Prognostic importance of hemoglobin in hypertensive patients with electrocardiographic left ventricular hypertrophy: the Losartan Intervention For End point reduction in hypertension (LIFE) study.

BACKGROUND: The prognostic importance of hemoglobin is controversial. We investigated the prognostic importance of baseline and in-treatment hemoglobin in the LIFE study. METHODS: Eight thousand one hundred ninety-four LIFE patients with hypertension and left ventricular hypertrophy with available baseline hemoglobin measurements were randomized to losartan- or atenolol-based treatment and followed for 4.8 years for end points of all-cause mortality and composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. RESULTS: U-shaped relations were observed between deciles of baseline hemoglobin and all-cause mortality and the composite end point. In univariate Cox models, baseline hemoglobin in the lowest gender-specific decile (women/men: <12.5/13.4 g/dL) was associated with all-cause mortality (hazard ratio [HR] 2.01, 95% CI 1.64-2.64) and the composite end point (HR 1.53, 95% CI 1.27-1.85, both P < .001), whereas hemoglobin in the highest gender-specific decile (women/men: > or =15.0/16.2 g/dL) was not. The decrease in hemoglobin was higher (P < .001) in patients allocated to losartan- (14.3-13.8 g/dL) versus atenolol-based treatment (14.3-14.0 g/dL). In Cox models with the same gender-specific definitions for high and low hemoglobin as time-varying covariates with adjustment for treatment allocation and established risk factors and diseases, hemoglobin in the lowest decile was associated with higher rates of all-cause mortality (HR 3.03, 95% CI 1.89-4.85, P < .001) and the composite end point (HR 1.36, 95% CI 1.08-1.71, P < .01), whereas hemoglobin in the highest decile was not. CONCLUSIONS: After adjusting for other risk factors, relatively low, but not high, hemoglobin during antihypertensive treatment was associated with higher incidence of all-cause mortality and the composite end point.

Predictors of cardiovascular events in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention for Endpoint reduction in hypertension study.

OBJECTIVE: We assessed readily available patient characteristics, including albuminuria (not included in traditional cardiovascular risk scores), as predictors of cardiovascular events in hypertension with left ventricular hypertrophy (LVH) and developed risk algorithms/scores for outcomes. METHODS: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study compared effects of losartan-based versus atenolol-based therapy on cardiovascular events in 9193 patients with hypertension and LVH. Univariate and multivariate analyses identified baseline variables with significant impact on development of the primary composite endpoint (cardiovascular death, stroke and myocardial infarction) and its components. Multivariate analysis used a Cox regression model with stepwise selection process. Risk scores were developed from coefficients of risk factors from the multivariate analysis, validated internally using naïve and jack-knife procedures, checked for discrimination and calibration, and compared with Framingham coronary heart disease and other risk scores. RESULTS: LIFE risk scores showed increasing endpoint rates with increasing quintile (first to fifth quintile, composite endpoint 2.8-26.7%, cardiovascular death 0.5-14.4%, stroke 1.2-11.3%, myocardial infarction 1.4-8.1%) and were confirmed with a jack-knife approach that adjusts for potentially optimistic bias. The Framingham coronary heart disease and other risk scores overestimated risk in lower risk patients and underestimated risk in higher risk patients, except for myocardial infarction. CONCLUSION: A number of patient characteristics predicted cardiovascular events in patients with hypertension and LVH. Risk scores developed from these patient characteristics, including albuminuria, strongly predicted outcomes and may improve risk assessment of patients with hypertension and LVH and planning of clinical trials.

Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study.

BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction in Hypertension (LIFE) study included 9193 patients 55 to 80 years of age with essential hypertension and ECG LV hypertrophy by gender-adjusted Cornell product (CP) (RaVL+SV(3) [+6 mm in women]). QRS duration>2440 mm x ms) and/or Sokolow-Lyon voltage (SLV) (SV1+RV(5/6)>38 mm). During follow-up (mean, 4.8 years), 190 patients (2%) experienced SCD. In time-dependent Cox analyses, absence of in-treatment LV hypertrophy was associated with a decreased risk of SCD: every 1-SD-lower in-treatment CP (1050 mm x ms) was associated with a 28% lower risk of SCD (hazard ratio [HR], 0.72; 95% CI, 0.66 to 0.79) and 1-SD-lower SLV (10.5 mm) with a 26% lower risk (HR, 0.74; 95% CI, 0.65 to 0.84). After adjustment for time-varying systolic and diastolic blood pressures, treatment allocation, age, gender, baseline Framingham risk score, ECG strain, heart rate, urine albumin/creatinine ratio, smoking, diabetes, congestive heart failure, coronary heart disease, atrial fibrillation, and occurrence of myocardial infarction, atrial fibrillation, heart failure, and noncardiovascular death, both in-treatment CP and SLV remained predictive of SCD: each 1-SD-lower CP was associated with a 19% lower risk of SCD (HR, 0.81; 95% CI, 0.73 to 0.90) and 1-SD-lower SLV with an 18% lower risk (HR, 0.82; 95% CI, 0.70 to 0.98). Absence of in-treatment LV hypertrophy by both SLV and CP was associated with a 30% lower risk of SCD (HR, 0.70; 95% CI, 0.54 to 0.92). CONCLUSIONS: Absence of in-treatment ECG LV hypertrophy is associated with reduced risk of SCD independently of treatment modality, blood pressure reduction, prevalent coronary heart disease, and other cardiovascular risk factors in hypertensive patients with LV hypertrophy.

Combination of the electrocardiographic strain pattern and albuminuria for the prediction of new-onset heart failure in hypertensive patients: the LIFE study.

BACKGROUND: Although albuminuria and the electrocardiographic (ECG) strain pattern each predict development of heart failure (HF), whether combining albuminuria and strain improves prediction of new HF is unclear. METHODS: The relation of ECG strain and albuminuria to new-onset HF was examined in 7,786 hypertensive patients with no history of HF, who were randomly assigned to treatment with losartan or atenolol. Albuminuria was defined by a urine albumin/creatinine ratio >30.94 mg/g. RESULTS: During a mean follow-up of 4.7 +/- 1.1 years, new-onset HF occurred in 231 patients (3.0%). Five-year HF rate was highest when both strain and albuminuria were present (10.4%), intermediate when only ECG strain (8.0%) or albuminuria (4.9%) was present, and lowest when neither strain nor albuminuria was present at baseline (1.8%, P < 0.0001). In Cox multivariable analyses, controlling for HF risk factors, treatment assignment and baseline severity of ECG left ventricular hypertrophy (LVH) by both Sokolow-Lyon voltage and Cornell product, ECG strain and albuminuria remained significant predictors of incident HF, with the presence of both strain and albuminuria associated with the highest risk (HR 2.8, 95% CI 1.8-4.4) and the presence of only strain (HR 2.6, 95% CI 1.7-4.0) or albuminuria (HR 2.1, 95% CI 1.5-2.8) with intermediate risk of new HF compared with the absence of both strain and albuminuria. CONCLUSIONS: The combination of albuminuria and ECG strain identifies hypertensive patients at an increased risk of developing HF in the setting of aggressive blood pressure lowering, independent of treatment modality and of other risk factors for HF.

Impact of diabetes mellitus on regression of electrocardiographic left ventricular hypertrophy and the prediction of outcome during antihypertensive therapy: the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study.

BACKGROUND: Diabetes mellitus is associated with increased cardiovascular (CV) morbidity and mortality and with greater ECG left ventricular hypertrophy (LVH); however, it is unclear whether diabetes attenuates regression of hypertensive LVH and whether regression of ECG LVH has similar prognostic value in diabetic and nondiabetic hypertensive individuals. METHODS AND RESULTS: A total of 9193 hypertensive patients (1195 with diabetes) in the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study were treated with losartan- or atenolol-based regimens and followed up with serial ECG and blood pressure determinations at baseline and 6 months and then yearly until death or study end. ECG LVH was defined with gender-adjusted Cornell voltage-duration product (CP) criteria >2440 mm . ms. After a mean follow-up of 4.8+/-0.9 years, patients with diabetes had less regression of CP LVH (-138+/-866 versus -204+/-854 mm . ms, P<0.001), remained more likely to have LVH by CP (56.0% versus 48.1%, P<0.001), and had higher rates of CV death, myocardial infarction, stroke, and all-cause mortality and of the LIFE composite end point of CV death, myocardial infarction, or stroke. In multivariable Cox proportional hazards models, in-treatment regression or absence of ECG LVH by CP was associated with between 17% and 35% reductions in event rates in patients without diabetes but did not significantly predict outcome in patients with diabetes. CONCLUSIONS: Hypertensive patients with diabetes have less regression of CP LVH in response to antihypertensive therapy than patients without diabetes, and regression of ECG LVH is less useful as a surrogate marker of outcomes in hypertensive patients with diabetes. These findings may in part explain the higher CV morbidity and mortality in hypertensive patients with diabetes, and the absence of a demonstrable improvement in prognosis in diabetic patients in response to regression of ECG LVH suggests a more complex interrelation between underlying LV structural and functional abnormalities and outcome in these patients.

World Health Organization (WHO) and International Society of Hypertension (ISH) risk prediction charts: assessment of cardiovascular risk for prevention and control of cardiovascular disease in low and middle-income countries.

Cardiovascular disease (CVD) is the leading cause of the growing global disease burden due to non-communicable diseases. For successful prevention and control of CVD, strategies that focus on individuals need to complement population-wide strategies. Strategies that focus on individuals are cost effective only when targeted at high-risk groups. Risk prediction tools that easily and accurately predict an individual's absolute risk of CVD are key to targeting limited resources at high-risk individuals who are likely to benefit the most. Health systems in low-income countries do not have the basic infrastructure facilities to support resource-intensive risk prediction tools, particularly in primary healthcare. The WHO/ISH charts presented here, enable the prediction of future risk of heart attacks and strokes in people living in low and middle income countries, for the first time. Furthermore, since the charts use simple variables they can be applied even in low resource settings. Thus the WHO/ISH risk predication charts and the accompanying guideline will improve the effectiveness of cardiovascular risk management even in settings which do not have sophisticated technology.

Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies.

OBJECTIVE: To investigate whether a threshold exists for cardiovascular risk in type 2 diabetic patients with hypertension, the association between renal function and cardiovascular risk was examined across the entire physiological range of serum creatinine. DESIGN AND METHODS: The RENAAL and LIFE studies enrolled 1513 and 1195 patients with type 2 diabetes and hypertension, respectively. The relationship between baseline serum creatinine and the risk for a composite outcome of myocardial infarction, stroke or cardiovascular death was examined using Cox regression models. To adjust for heterogeneity between studies and treatment groups, these factors were included as strata when applicable. The analyses were conducted with adjustment for age, gender, smoking, alcohol use, blood pressure, heart rate, total and high-density lipoprotein (HDL) cholesterol, hemoglobin, albuminuria and prior cardiovascular disease. RESULTS: The hazard ratios across the baseline serum creatinine categories < 0.9 mg/dl, 0.9-1.2 mg/dl, 1.2-1.6 mg/dl, 1.6-2.8 mg/dl and >or= 2.8 mg/dl were 0.51 (95% confidence interval 0.34, 0.74), 0.74 (0.55, 1.00), 1.00 (reference), 1.24 (0.96, 1.59) and 1.67 (1.17, 2.91), respectively. Baseline serum creatinine (per mg/dl) strongly predicted the composite cardiovascular endpoint in LIFE [2.82(1.74,4.56), P < 0.001], RENAAL [1.41(1.12,1.79), P < 0.001], as well as the combined studies [1.51(1.21,1.87), P < 0.001]. CONCLUSION: A progressively higher risk for the composite cardiovascular endpoint was observed with incremental baseline serum creatinine in type 2 diabetic patients with hypertension, even within the normal range. Thus, there appears to be no serum creatinine threshold level for an increased cardiovascular risk. Baseline serum creatinine was a major independent risk factor for cardiovascular disease (www.ClinicalTrials.gov number NCT00308347).

Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study.

OBJECTIVE: Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to its influence on UACR, and 4) reduction in albuminuria reduced cardiovascular events. RESEARCH DESIGN AND METHODS: In 1,063 patients with diabetes, hypertension, and left ventricular hypertrophy, UACR was measured for a mean of 4.7 years. The primary composite end point included cardiovascular death, myocardial infarction, and stroke. Cox models were run including and excluding baseline and time-varying UACR. RESULTS: Increasing baseline albuminuria related to increased risk for cardiovascular events. Reductions in UACR at years 1 and 2 were approximately 33% for losartan vs. 15% for atenolol (P < 0.001). Benefits of losartan seem to be most prominent in patients with the highest level of baseline UACR, although treatment by albuminuria interaction was only significant for total mortality. Approximately one-fifth of the superiority of losartan was explained by the greater reduction of albuminuria. Risk of the primary end point was related to the in-treatment UACR. CONCLUSIONS: Lowering of albuminuria in patients with hypertension and diabetes appears to be beneficial and should be the subject of additional study in future clinical trials.