Lower Risk Of Cardiovascular Mortality Research Articles

Role of Niacin in Current Clinical Practice: A Systematic Review

BackgroundNiacin, a potent high-density lipoprotein cholesterol-raising drug, seems an attractive approach to reduce cardiac events in patients with or at risk of atherosclerotic cardiovascular disease. However, previous evidence for niacin has been challenged recently by negative outcomes in 2 large, randomized, controlled trials comparing niacin to placebo with background statin therapy. We studied the currently available evidence for the role of niacin treatment for reducing the risk of cardiovascular events in current practice. MethodsA systematic review of randomized controlled trials in the MEDLINE, EMBASE, CINAHL, and Cochrane databases comparing niacin alone or combined with statin therapy was performed. We extracted trial level data, including basic characteristics and number of patients enrolled, duration of follow up, occurrence of adverse events, and cardiovascular-related outcomes. Random effects meta-analysis was conducted to estimate the risk ratio (RR) for individual trial endpoints. ResultsThirteen trials (N = 35,206) were selected for final analysis. The mean follow-up duration was 32.8 months. Overall, niacin led to significant increases in serum high-density lipoprotein cholesterol levels from baseline trial enrolment by 21.4%, 9.31 (95% confidence interval [CI] 5.11-13.51) mg/dL. However, we did not observe any differences in all-cause mortality rates (RR 0.99; 95% CI 0.88-1.12) between niacin and control arms. Further, niacin treatment was associated with a trend toward lower risk of cardiovascular mortality (RR 0.91; 95% CI 0.81-1.02), coronary death (RR 0.93; 95% CI 0.78-1.10), nonfatal myocardial infarction (RR 0.85; 95% CI 0.73-1.0), revascularization (coronary and noncoronary) (RR 0.83; 95% CI 0.65-1.06), and stroke (RR 0.89; 95% CI 0.72-1.10), compared with control. ConclusionNiacin therapy does not lead to significant reductions in total or cause-specific mortality or recurrent cardiovascular events among persons with or at risk of atherosclerotic cardiovascular disease.

Lower thigh muscle mass is associated with all-cause and cardiovascular mortality in elderly hemodialysis patients.

Higher body mass index appears protective in hemodialysis patients, although it remains to be determined which component of muscle or fat mass is primarily associated with this survival advantage. Eighty-one hemodialysis patients in our institution were prospectively followed from July 2011 to August 2015. Muscle and fat mass were evaluated by measuring the cross-sectional areas of the thigh and abdomen using computed tomography. The relationship between muscle and fat mass, and all-cause and cardiovascular mortality was studied using the Kaplan-Meier analyses and multivariate Cox proportional hazard models. During more than 4 years of follow-up, 26 patients (32%) died. In the Kaplan-Meier curve analyses, lower thigh muscle mass was significantly associated with all-cause and cardiovascular mortality (log-rank test, P<0.01 and P<0.001, respectively), but there was no such association with thigh fat, abdominal muscle and fat mass levels. In multivariate Cox proportional hazard models, each 0.1 cm2/kg increase in the thigh muscle area adjusted by dry weight was associated with an estimated 22% lower risk of all-cause mortality (95% confidence interval (95% CI), 0.64-0.95, P<0.05) and a 30% lower risk of cardiovascular mortality (95% CI, 0.54-0.90, P<0.01). Lower thigh muscle mass is significantly associated with all-cause and cardiovascular mortality in hemodialysis patients. Our findings indicate the importance of focusing on the muscle mass of lower extremities to predict the clinical outcomes of hemodialysis patients.

Bisphosphonates for cardiovascular risk reduction: A systematic review and meta-analysis

Background and aimsBisphosphonates might be effective in reducing cardiovascular events due to their ability to reduce calcification in arterial walls. We aimed to investigate the effects of treatment with bisphosphonates on the prevention of atherosclerotic processes and cardiovascular disease. MethodsPubmed, Embase and the Cochrane Library were systematically reviewed by two independent investigators for randomized controlled studies published up to January 2016, in which the effect of bisphosphonates on arterial wall disease, cardiovascular events, cardiovascular mortality or all-cause mortality were reported. There was no restriction for the type of population used in the trials. Random-effects models were used to calculate the pooled estimates. Results61 trials reporting the effects of bisphosphonates on the outcomes of interest were included. Bisphosphonates had beneficial effects on arterial wall disease regarding arterial calcification (pooled mean percentage difference of 2 trials −11.52 (95% CI -16.51 to −6.52, p < 0.01, I2 13%), but not on arterial stiffness (pooled mean percentage difference of 2 trials −2.82; 95% CI -10.71–5.07; p = 0.48, I2 59%). No effect of bisphosphonate treatment on cardiovascular events was found (pooled RR of 20 trials 1.03; 95% CI 0.91–1.17, I2 16%), while a lower risk for cardiovascular mortality was observed in patients treated with bisphosphonates (pooled RR of 10 trials 0.81; 95% CI 0.64–1.02; I2 0%) although not statistically significant. Patients treated with bisphosphonates had a reduced risk of all-cause mortality (pooled RR of 48 trials 0.90; 95% CI 0.84–0.98; I2 53%). ConclusionsIn this systematic review and meta-analysis it is shown that bisphosphonates reduce arterial wall calcification but have no effect on arterial stiffness or on cardiovascular events. Bisphosphonates tend to reduce the risk of cardiovascular mortality and reduce all-cause mortality in various patient groups, including osteoporosis and cancer patients.

Dark chocolate attenuates intracellular pro-inflammatory reactivity to acute psychosocial stress in men: A randomized controlled trial

Flavanol-rich dark chocolate consumption relates to lower risk of cardiovascular mortality, but underlying mechanisms are elusive. We investigated the effect of acute dark chocolate consumption on inflammatory measures before and after stress.Healthy men, aged 20–50years, were randomly assigned to a single intake of either 50g of flavanol-rich dark chocolate (n=31) or 50g of optically identical flavanol-free placebo-chocolate (n=34). Two hours after chocolate intake, both groups underwent the 15-min Trier Social Stress Test. We measured DNA-binding-activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, as well as plasma and whole blood mRNA levels of the pro-inflammatory cytokines IL-1β and IL-6, and the anti-inflammatory cytokine IL-10, prior to chocolate intake as well as before and several times after stress. We also repeatedly measured the flavanol epicatechin and the stress hormones epinephrine and cortisol in plasma and saliva, respectively.Compared to the placebo-chocolate-group, the dark-chocolate-group revealed a marginal increase in IL-10 mRNA prior to stress (p=0.065), and a significantly blunted stress reactivity of NF-κB-BA, IL-1β mRNA, and IL-6 mRNA (p’s⩽0.036) with higher epicatechin levels relating to lower pro-inflammatory stress reactivity (p’s⩽0.033). Stress hormone changes to stress were controlled. None of the other measures showed a significant chocolate effect (p’s⩾0.19).Our findings indicate that acute flavanol-rich dark chocolate exerts anti-inflammatory effects both by increasing mRNA expression of the anti-inflammatory cytokine IL-10 and by attenuating the intracellular pro-inflammatory stress response. This mechanism may add to beneficial effects of dark chocolate on cardiovascular health.

Prognostic impact of ß-blocker use in patients with stable coronary artery disease

ObjectiveTo assess the association of ß-blocker use with cardiovascular mortality in patients with stable coronary artery disease (CAD).MethodsWe analysed the data of 4184 outpatients included in a prospective cohort study...

Uric Acid Levels, Kidney Function, and Cardiovascular Mortality in US Adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002

Chronic kidney disease (CKD) and hyperuricemia often coexist, and both conditions are increasing in prevalence in the United States. However, their shared role in cardiovascular risk remains highly debated. Cross-sectional and longitudinal. Participants in the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2002 (n = 10,956); data were linked to mortality data from the National Death Index through December 31, 2006. Serum uric acid concentration, categorized as the sex-specific lowest (< 25th), middle (25th- < 75th), and highest (≥ 75th) percentiles; and kidney function assessed by estimated glomerular filtration rate (eGFR) based on the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation and urinary albumin-creatinine ratio (ACR). Cardiovascular death and all-cause mortality. Uric acid levels were correlated with eGFR(cr-cys) (r = -0.29; P < 0.001) and were correlated only slightly with ACR (r = 0.04; P < 0.001). There were 2,203 deaths up until December 31, 2006, of which 981 were due to cardiovascular causes. Overall, there was a U-shaped association between uric acid levels and cardiovascular mortality in both women and men, although the lowest risk of cardiovascular mortality occurred at a lower level of uric acid for women compared with men. There was an association between the highest quartile of uric acid level and cardiovascular mortality even after adjustment for potential confounders (HR, 1.48; 95% CI, 1.13-1.96), although this association was attenuated after adjustment for ACR and eGFR(cr-cys) (HR, 1.25; 95% CI, 0.89-1.75). The pattern of association between uric acid levels and all-cause mortality was similar. GFR not measured; mediating events were not observed. High uric acid level is associated with cardiovascular and all-cause mortality, although this relationship was no longer statistically significant after accounting for kidney function.

Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI: a systematic review and meta-analysis

AimThe benefit of preventive percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) has been shown in randomised trials. However, all the randomised trials are underpowered to detect benefit...

Circulation: Heart Failure Editors’ Picks

Summary : Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year. The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure–volume measurements, exercise testing, and cardiac MRI before and after the training. To the authors’ knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans. After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume. Conversely, alagebrium had little effect on exercise capacity or LV geometry. However, alagebrium showed a modest improvement in LV stiffness compared with placebo. This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training. Conclusions : Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.1 Summary : Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival. On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing. This single-center study examined the association of …

The Better Outcomes Associated with Warfarin use in Patients with Heart Failure in Either Atrial Fibrillation or Sinus Rhythm

PP-051 Warfarin use and associated outcomes in patients with chronic heart failure (HF) have not been well described previously. We hypothesized that warfarin is associated with lower risks of cardiovascular mortality in patients with sinus rhythm, atrial fibrillation and pacemaker rhythm. We

Association Between the Volume of Inpatient Rehabilitation Therapy and the Risk of All-Cause and Cardiovascular Mortality in Patients With Ischemic Stroke

ObjectiveTo investigate the relationship between the volume of inpatient rehabilitation therapy and mortality among patients with acute ischemic stroke, as well as to assess whether the association varies with respect to stroke severity. DesignA retrospective study with a cohort of consecutive patients who had acute ischemic stroke between January 1, 2008, and June 30, 2009. SettingReferral medical center. ParticipantsAdults with acute ischemic stroke (N=1277) who were admitted to a tertiary hospital. InterventionsNot applicable. Main Outcome MeasureStroke-related mortality. ResultsDuring the median follow-up period of 12.3 months (ranging from January 1, 2008, to December 31, 2009), 163 deaths occurred. Greater volume of rehabilitation therapy was associated with a reduced risk of all-cause and cardiovascular mortality (P for trend <.001 for both). Compared with the first tertile, the third tertile of rehabilitation volume was associated with a 55% lower risk of all-cause mortality (hazard ratio [HR]=.45; 95% confidence interval [CI], .30–.65) and a 50% lower risk of cardiovascular mortality (HR=.50; 95% CI, .31–.82). The association did not vary with respect to stroke severity (P for interaction = .45 and .73 for all-cause and cardiovascular mortality, respectively). ConclusionsThe volume of inpatient rehabilitation therapy and mortality were significantly inversely related in the patients with ischemic stroke. Thus, further programs aimed at promoting greater use of rehabilitation services are warranted.

Dairy products are differently related to plasma lipids and cardiovascular risk, depending on their fat content

Purpose: Fat content of dairy foods is diverse, potentially leading to varying effects on cardiovascular risk. We studied relationships of low- and high-fat dairy products with lipids and level of cardiovascular risk, in a cross-sectional population survey conducted in three French areas. Methods: A sample of 3078 participants aged 35-64 years, was randomly selected in 2005-2007 by drawing on polling lists. Participants underwent a standardised cardiovascular risk assessment and were asked to prospectively record the types and amounts of foods and beverages they consumed over a three-consecutive day period. All records were checked by a dietician. Dairy products were separated into two groups: the low-fat group comprised milk (including milk from desserts and beverages), yogurts and cottage cheese, whereas other cheeses formed the high-fat group. The SCORE algorithm was used to assess 10-year risk of cardiovascular mortality. Results: The sample included 50% of men and women with a median age of 50.4 years. The median levels of lipids were 5.67 mmol/l (total cholesterol), 3.56 mmol/l (LDL-cholesterol), 1.42 mmol/l (HDL-cholesterol) and 1.12 mmol/l (triglycerides). Forty three percent of the sample had a 10-year risk of cardiovascular mortality ≥ 2%. After adjustment (including level of education, physical activity and a diet quality score), the probability of an increased 10-year risk of cardiovascular mortality (SCORE ≥ 2%) decreased from the bottom first to the top fourth quartile (Q) of low-fat dairy product intake: ORQ1 (odds ratio)=1; ORQ2=0.74 [95% confidence interval: 0.60-0.91], ORQ3=0.65 [0.52-0.80], and ORQ4=0.58 [0.47-0.72] for the first, second, third and fourth quartile, respectively. Results were notably different for high-fat dairy product intake: ORQ2=1.04 [0.84-1.28]; ORQ3=0.96 [0.78-1.19]; ORQ4=1.23 [1.00-1.52]. Intake of low-fat dairy products was inversely associated with low LDL-cholesterol, but no significant relationship was found with HDL-cholesterol or triglycerides. None of the lipid parameters was significantly associated with the consumption of high-fat dairy products. Conclusions: Participants with the highest intake of low-fat dairy products were at the lowest risk of cardiovascular mortality, as assessed by the SCORE equation, and they exhibited the best LDL-cholesterol profile. Despite extensive adjustment, this observation may still be related to differences in lifestyle habits. No significant association was observed between cardiovascular risk and high-fat dairy products.

How Estrogens Prevent From Lipid-Induced Insulin Resistance

Premenopausal women have generally lower amounts of central adipose tissue and lower incidence of obesity-related metabolic abnormalities, which are frequently summarized as metabolic syndrome. Classical components of the metabolic syndrome are linked to impaired insulin action, also termed insulin resistance. Several mechanisms are currently discussed to underlie insulin resistance and comprise abnormal lipid metabolism with ectopic accumulation of triacylglycerols (TAGs), termed lipid overflow and lipotoxicity (1, 2), abnormal mitochondrial function (3), and oxidative stress as well as inflammation and endoplasmic reticulum stress (4). All these abnormalities can contribute to increased cardiovascular morbidity and mortality. Indeed, it is well known that premenopausal women exhibit a lower risk of cardiovascular mortality than ageand body-mass-index–matched men. This protective effect is lost in the postmenopausal state, when the circulating estrogen levels decline and women become more susceptible to obesity-associated insulin resistance. Decreasing estrogen production in female animal models by ovariectomy leading to a surgical menopause or by gene manipulation leading to down-regulation of estrogen synthesis has similar effects. These observations imply a relevant role of estrogens in the regulation of glucose metabolism and in the pathogenesis of insulin resistance. During the reproductive period, 17s-ethinyl-estradiol is the predominant estrogen and exerts its physiological actions through the two estrogen receptors (ERs), ER and ER . Although estrogen mainly acts via nuclear estrogen-responsive elements and recruitment of other coregulatory proteins to regulate gene transcription in all metabolically important tissues, there is also evidence for nongenomic effects via membrane-bound ER (reviewed in Ref. 5). Global ER deletion leads to increased body weight and insulin resistance, suggesting that this receptor is of critical importance for the metabolic estrogen action. In adipose tissue, 17s-ethinyl-estradiol was found to prevent fat (TAG) accumulation due to suppression of its target gene, lipoprotein lipase (LPL) an enzyme catalyzing lipogenesis. Aside from lower lipogenesis, 17s-ethinyl-estradiol increases expression of hormone-sensitive lipase (HSL), resulting in increased lipolysis, and stimulates lipid oxidation by increasing phosphorylation of AMP-activated protein kinase (AMPK) and expression of peroxisome proliferator-activated receptorcoactivator 1 (PGC-1 ), and uncoupling protein 2 (UCP2) (5). In the liver, 17s-ethinyl-estradiol can reduce TAG accumulation, gluconeogenesis, and inflammatory pathways. Using ER inactivation showed that estrogens modulate functions of macrophages, of pancreatic s-cells to maintain insulin secretion via an antiapoptotic activity, and of hypothalamic neurons involved in energy homeostasis, maybe by regulating caloric intake and/or energy expenditure. In skeletal muscle, 17s-ethinyl-estradiol improves glucose disposal by modulating expression and the insulin-sensitive trafficking of glucose transporters [glucose transporter 4, (GLUT4)]. Finally, 17s-ethinyl-estradiol is thought to protect endothelial function and induce antiinflammatory effects in vascular tissue. Despite its multiplicity and complexity of effects, the exact molecular mechanisms linking 17s-ethinyl-estradiol with improved insulin signaling and whole-body glucose and lipid disposal have not yet been resolved.

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53-0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44-1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21-0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.

I am 80 going on 18: exercise and the fountain of youth

aging is associated with physiological decline. To slow or reverse this decline, humans have searched for various “fountains of youth” since the dawn of history ([4][1]). Most recently, aging has become medicalized and interventions, such as caloric restriction, stem cells, hormonal anti-aging

Modest Increase in Peak VO 2 Is Related to Better Clinical Outcomes in Chronic Heart Failure Patients

Background— The prognostic ability of a single measurement of peak oxygen uptake (VO 2 ) is well established in patients with chronic heart failure. The relation between a change in peak VO 2 and clinical outcomes is not well defined. Methods and Results— This investigation determined whether an increase in peak VO 2 was associated with a lower risk of the primary end point of time to all-cause mortality or all-cause hospitalization and 3 secondary end points. In Heart Failure and a Controlled Trial to Investigate Outcomes of Exercise Training, an exercise training trial for patients with systolic heart failure, cardiopulmonary exercise tests were performed at baseline and ≈3 months later in 1620 participants. Median peak VO 2 in the combined sample increased from 15.0 (11.9–18.0 Q1–Q3) to 15.4 (12.3–18.7 Q1–Q3) mL·kg −1 ·min −1 . Every 6% increase in peak VO 2, adjusted for other significant predictors, was associated with a 5% lower risk of the primary end point (hazard ratio=0.95; CI=0.93–0.98; P &lt;0.001); a 4% lower risk of the secondary end point of time to cardiovascular mortality or cardiovascular hospitalization (hazard ratio=0.96; CI=0.94–0.99; P &lt;0.001); an 8% lower risk of cardiovascular mortality or heart failure hospitalization (hazard ratio=0.92; CI=0.88–0.96; P &lt;0.001); and a 7% lower all-cause mortality (hazard ratio=0.93; CI=0.90–0.97; P &lt;0.001). Conclusions— Among patients with chronic systolic heart failure, a modest increase in peak VO 2 over 3 months was associated with a more favorable outcome. Monitoring the change in peak VO 2 for such patients may have benefit in assessing prognosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00047437.

PAR-1 antagonists: current state of evidence

Vorapaxar (SCH 530348) and atopaxar (E5555) are oral protease-activated receptor-1 (PAR-1) antagonists with high bioavailability. They inhibits thrombin induced platelet aggregation by competitively inhibiting PAR-1. We systematically evaluated the evidence for the efficacy and safety of all PAR-1 antagonists as well as for the individual drugs vorapaxar and atopaxar in different databases-PubMed, EMBASE, Scopus, and Cochrane register of Controlled Clinical Trials (CENTRAL).We selected randomized controlled trials of PAR-1 antagonists that reported on cardiovascular mortality as a clinical outcome. The random-effects Mantel-Haenszel model was used to evaluate the effect of PAR-1 antagonists on cardiovascular mortality. Seven trials were selected (N = 42,355) for analysis. PAR-1 antagonists as a class, as well as individually, were associated with a non-significant numerically lower risk of cardiovascular mortality than that seen with agents used in the control group; RR, 0.93; 95% CI, 0.83-1.04; P = 0.20). No heterogeneity was noted. However, PAR-1 antagonists also appeared to increase the risk of bleeding significantly. PAR-1 antagonists appear to be associated with some reduction in the risk of cardiovascular mortality; however the significantly higher bleeding risk noted with PAR-1 antagonists appear to mandate a very careful selection of patients that may benefit without a substantially increased risk of bleeds.

Metabolic Syndrome, Testosterone, and Cardiovascular Mortality in Men

Interactions among testosterone, metabolic syndrome (MetS), and mortality risk in men remain to be elucidated. To examine relationships among testosterone, MetS, and cardiovascular mortality risk in U.S. men, middle-aged and older. The analysis included the men aged 40 years and above in Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey (NHANES III). Serum testosterone and sex hormone binding globulin were measured, and free testosterone and bioavailable testosterone were calculated. MetS was determined according to the Adult Treatment Panel III (ATP-III) criteria. Cardiovascular and other causes of mortality were obtained from the NHANES III-linked follow-up file through December 31, 2006. Multivariate Cox regression models were applied to assess associations of interest. Of 596 men included in the analysis, 187 men were found to have MetS. During a median follow-up of 15.6 years, 97 men died of cardiovascular causes (cardiovascular mortality rate: 9.84 and 5.77 per 1,000 person-years for those with and without MetS, respectively). Higher calculated bioavailable testosterone (CBT) was associated with a lower odds of MetS (odds ratio: 0.80 for each ng/mL, 95% confidence interval [CI]: 0.76-0.84, P < 0.001) and lower risk of cardiovascular mortality (hazard ratios [HRs]: 0.72 for each log ng/mL, 95% CI: 0.54-0.96, P = 0.03) in subjects with MetS. The influence of CBT was not observed in those without MetS (HR: 0.84 for each log ng/mL, 95% CI: 0.68-1.04, P = 0.10). The combination of lower bioavailable testosterone and ATP-III-defined MetS is associated with an increased cardiovascular mortality in the men aged 40 years and above.

Revised guidelines for cardiovascular risk management — time to stop medication? A practice-based intervention study

According to the new Dutch guideline for cardiovascular risk management, patients with a low risk of cardiovascular mortality may have insufficient benefit to warrant medication. Therefore, numerous patients per general practice may be treated unnecessarily. To explore the feasibility and consequences of a re-evaluation programme for patients without target organ damage who were treated for hypertension and/or hypercholesterolaemia. Practice-based intervention study in six general practices. Patients treated for hypertension and/or hypercholesterolaemia without target organ damage (n = 833) were invited to re-evaluate their cardiovascular risk and were advised whether or not to stop medication. Patients who discontinued medication were followed for 6 months. To determine indicators for successful stopping, logistic regression analyses were performed, and differences between practices were analysed. About two-thirds of the patients were re-evaluated and 61% of them had a low calculated risk, especially younger patients, females, and non-smokers. Of these, 42% were advised to stop medication, especially younger patients and non-smokers. Of those who discontinued medication, 40% had restarted within 6 months. After 6 months, 80 of the 833 patients (9.6%) had not restarted medication. There were no important side effects related to stopping medication. Over 50% of patients without target organ damage treated for hypertension and/or hypercholesterolaemia may have insufficient benefit to warrant medication. Younger patients, females, and non-smokers in particular are more likely to have an insufficient indication for medication. GPs' and nurse practitioners' views seem to play a role in advising to stop or to restart medication.

Changes in electrocardiographic left ventricular hypertrophy and risk of major cardiovascular events in isolated systolic hypertension: The LIFE study

The predictive value of changes in the severity of electrocardiographic left ventricular hypertrophy (ECG-LVH) during antihypertensive therapy remains unclear in isolated systolic hypertension (ISH). In a Losartan Intervention For Endpoint reduction in hypertension substudy, we included 1320 patients aged 54-83 years with systolic blood pressure (BP) of 160-200 mm Hg, diastolic BP <90 mm Hg and ECG-LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria, randomized to losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point of cardiovascular death, non-fatal myocardial infarction (MI) or stroke occurred in 179 (13.6%) patients. In Cox regression models controlling for treatment, Framingham risk score, as well as baseline and in-treatment BP, less severe in-treatment ECG-LVH by Cornell product and Sokolow-Lyon voltage was associated with 17 and 25% risk reduction for the composite end point (adjusted hazard ratio (HR) 0.83, 95% confidence interval (95% CI:) 0.75-0.92, P=0.001 per 1050 mm × ms (1 s.d.) lower Cornell product; and HR 0.75, 95% CI: 0.65-0.87, P<0.001 per 10.5 mm (1 s.d.) lower Sokolow-Lyon voltage). In parallel analyses, lower Cornell product and Sokolow-Lyon voltage were associated with lower risks of cardiovascular mortality and MI, and lower Sokolow-Lyon voltage with lower risk of stroke. Lower Cornell product and Sokolow-Lyon voltage during antihypertensive therapy are associated with lower likelihoods of cardiovascular events in patients with ISH.

Serial evaluation of electrocardiographic left ventricular hypertrophy for prediction of risk in hypertensive patients

Background Although the presence and severity of electrocardiographic (ECG) left ventricular hypertrophy (LVH) have been associated with an increased risk of cardiovascular (CV) morbidity and mortality, the relationship of regression of ECG LVH during antihypertensive therapy to CV risk has only recently been examined. Methods Electrocardiographic LVH was evaluated over time in 9193 hypertensive patients enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension study. Patients were treated with losartan- or atenolol-based regimens and followed with serial ECGs at 6 months and then yearly until death or study end. Electrocardiographic LVH was measured using gender-adjusted Cornell product (RaVL + SV3 [+6 mm in women]) ⁎ QRS duration) and Sokolow-Lyon voltage (SV1 + RV5/6). Results After mean (SD) follow-up of 4.8 (0.9) years, the Losartan Intervention for Endpoint Reduction in Hypertension study composite end point of CV death, nonfatal myocardial infarction, or stroke occurred in 1096 patients. In Cox regression models controlling for treatment type, baseline Framingham risk score, baseline, and in-treatment blood pressure and for severity of baseline ECG LVH by Cornell product and Sokolow-Lyon voltage, lower in-treatment ECG LVH by Cornell product and Sokolow-Lyon voltage were associated with 14% and 17% lower rates, respectively, of the composite CV end point: adjusted hazard ratios (HRs) of 0.86 (95% confidence interval [CI], 0.82-0.90; P < .001) for every 1050 mm · ms (1 SD) decrease in Cornell product and 0.83 (95% CI, 0.78-0.88; P < .001) for every 10.5 mm (1 SD) decrease in Sokolow-Lyon voltage. In parallel analyses, lower Cornell product and Sokolow- Lyon voltage were each independently associated with lower risks of CV mortality (HR, 0.78; 95% CI, 0.73-0.83; P < .001; HR, 0.80; 95% CI, 0.73-0.87; P < .001), of myocardial infarction (HR, 0.90; 95% CI, 0.82-0.98; P = .011; HR, 0.90; 95% CI, 0.81-1.00; P = .043), and of stroke (HR, 0.90; 95% CI, 0.84-0.96; P = .002; HR, 0.81; 95% CI, 0.75-0.89; P < .001). Regression of ECG LVH was also associated with significantly reduced risks of sudden cardiac death, new-onset atrial fibrillation, hospitalization for heart failure, and new-onset diabetes mellitus. Conclusions Regression of ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria during antihypertensive therapy is associated with lower likelihoods of CV morbidity and mortality, all-cause mortality, and new-onset diabetes, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of ECG LVH may improve prognosis.