The association of grip strength with cardiovascular diseases and all-cause mortality in people with hypertension: Findings from the Prospective Urban Rural Epidemiology China Study.

BACKGROUND:Both hypertension and grip strength (GS) are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to affect CVD and all-cause mortality is unknown. This study sought to investigate the associations of GS with the risk of major CVD incidence, CVD mortality, and all-cause mortality in patients with hypertension.METHODS:GS was measured using a Jamar dynamometer (Sammons Preston, Bolingbrook, IL, USA) in participants aged 35-70 years from 12 provinces included in the Prospective Urban Rural Epidemiology China Study. Cox frailty proportional hazards models were used to examine the associations of GS and hypertension and the outcomes of all-cause mortality and CVD incidence/mortality.RESULTS:Among 39,862 participants included in this study, 15,964 reported having hypertension, and 9095 had high GS at baseline. After a median follow-up of 8.9 years (interquartile range, 6.7-9.9 years), 1822 participants developed major CVD, and 1250 deaths occurred (388 as a result of CVD). Compared with normotensive participants with high GS, hypertensive patients with high GS had a higher risk of major CVD incidence (hazard ratio (HR) = 2.39; 95% confidence interval (95%CI): 1.86-3.06; p < 0.001) or CVD mortality (HR = 3.11; 95%CI: 1.59-6.06; p < 0.001) but did not have a significantly increased risk of all-cause mortality (HR = 1.24; 95%CI: 0.92-1.68; p = 0.159). These risks were further increased if hypertensive participants whose GS level was low (major CVD incidence, HR = 3.31, 95%CI: 2.60-4.22, p < 0.001; CVD mortality, HR = 4.99, 95%CI: 2.64-9.43, p < 0.001; and all-cause mortality, HR = 1.93, 95%CI: 1.47-2.53, p < 0.001).CONCLUSION:The present study demonstrates that low GS is associated with the highest risk of major CVD incidence, CVD mortality, and all-cause mortality among hypertensive patients. High levels of GS appear to mitigate long-term mortality risk among hypertensive patients.

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants.

AIMS:Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated.METHODS AND RESULTS:After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years.CONCLUSION:The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.TRIAL REGISTRATION NUMBER:NCT00468923.

Efficacy and safety of rivaroxaban plus aspirin in women and men with chronic coronary or peripheral artery disease.

AIMS:The COMPASS trial demonstrated that the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease or peripheral artery disease by 24% during a mean follow-up of 23 months. We explored whether this effect varies by sex.METHODS AND RESULTS:The effects were examined in women and men using log-rank tests and Kaplan-Meier curve. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were obtained from stratified Cox proportional hazards models to explore subgroup effects including subgroup of women and men according to baseline modified REACH risk score. Of 27 395 patients randomized, 18 278 were allocated to receive rivaroxaban plus aspirin (n = 9152) or aspirin alone (n = 9126), and of these, 22.1% were women. Women compared with men had similar incidence rates for MACE and major bleeding but borderline lower rates for myocardial infarction (1.7% vs. 2.2%, P = 0.05). The effect of combination therapy compared with aspirin in women and men was consistent for MACE (women: 3.8% vs. 5.2%, HR 0.72, 95% CI 0.54-0.97; men: 4.2% vs. 5.5%, HR 0.76, 95% CI 0.66-0.89; P interaction 0.75) and major bleeding (women: 3.1% vs. 1.4%, HR 2.22, 95% CI 1.42-3.46; men: 3.2% vs. 2.0%, HR 1.60, 95% CI 1.29-1.97; P interaction 0.19). There was no significant interaction between randomized treatment and baseline modified REACH score above or below the median for MACE or major bleeding.CONCLUSION:In patients with stable coronary artery disease or peripheral artery disease, the combination of rivaroxaban (2.5 mg twice daily) and aspirin compared with aspirin alone appears to produce consistent benefits in women and men, independent of baseline cardiovascular risk.

Fruit, vegetable, and legume intake and the risk of all-cause, cardiovascular, and cancer mortality: A prospective study.

BACKGROUND & AIMS:Although fruits and vegetable consumption has been shown to be associated with lower risks of mortality, cancers, and cardiovascular disease (CVD), there are limited data from China on the shape of the association. This study aimed to quantify the relationship between levels of fruit, vegetable, and legume consumption with the risk of major CVD, CVD mortality, cancer incidence, cancer mortality, and all-cause mortality.METHODS:In the baseline survey, participants attended 1 of 115 (45 urban and 70 rural) communities from 12 provinces to complete a standardized questionnaire, and undergo a physical examination between 2005 and 2009, and were followed up till 2017 (for the current analysis). Diet was assessed through in-person interviews by using validated food-frequency questionnaires. The clinical outcomes were adjudicated centrally by trained physicians using standardized definitions. Cox frailty models were used to explore the associations between fruit, vegetable, and legume consumption with the risk of all-cause, CVD, and cancer mortality.RESULTS:A total of 41 243 participants were eligible for inclusion in the analyses. The average combined average daily intake of fruit, vegetable, and legume was 2.97 [standard deviation (SD) 1.22] servings per day. During a median follow-up of 8.9 years [interquartile range (IQR) 6.7-9.9 years], we recorded 1893 major CVDs, 794 cancer events, and 1324 deaths, with 411 CVD deaths and 429 cancer deaths. In the models adjusted for age, sex, and center (random effect), a higher total intake of fruit, vegetable, and legume was inversely associated with CVD mortality, cancer incidence, cancer mortality, and all-cause mortality. After adjusting for additional covariates, the associations were evidently attenuated and only the association with all-cause mortality (hazard ratio [HR] trend 0.92, 95% CI 0.86-0.98, p trend = 0.021) remained significant, with a non-significant trend for major CVD (HR trend 1.02, 95% CI 0.97-1.08, p trend = 0.449), CVD mortality (HR trend 0.94, 95% CI 0.84-1.06, p trend = 0.301), cancer incidence (HR trend 0.97, 95% CI 0.89-1.06, p trend = 0.540), or cancer mortality (HR trend 0.92, 95% CI 0.82-1.04, p trend = 0.174). Compared with the reference group, the risk of all-cause mortality was the lowest for four to five servings of total daily intake of fruit, vegetable, and legume (HR 0.73, 95% CI 0.55-0.97), and did not show a further decrease for the higher intake group. Separately, fruit intake was associated with a lower risk of all-cause mortality (HR trend 0.92, 95% CI 0.86-0.99, p trend = 0.020) and legume intake was associated with a lower risk of major CVD (HR trend 0.95, 95% CI 0.90-0.99, p trend = 0.028) and all-cause mortality (HR trend 0.94, 95% CI 0.89-0.99, p trend = 0.020) in the fully adjusted models.CONCLUSIONS:This prospective study suggests that Chinese people with daily consumption of four to five servings (equivalent to 500-625 g/day) of fruit, vegetable, and legume demonstrated the lowest mortality, which conveys an encouraging message to the public that lifestyle modification to increase fruit, vegetable, and legume intakes may have greater beneficial effects on reducing all-cause mortality.

Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline: The COMPASS MRI Substudy.

BACKGROUND AND PURPOSE:Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities.METHODS:Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities.RESULTS:At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests.CONCLUSIONS:Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Increased mortality in patients with secondary diagnosis of atrial fibrillation: Report from Chinese AF registry.

BACKGROUND:The relationship between mortality and the primary diagnosis in AF patients is poorly recognized. The purpose of the study is to compare the differences on mortality in patients with a primary or secondary diagnosis of AF and to identify risk factors amenable to treatment.METHODS:This was a prospective cohort study using data from the Chinese AF registry. For admitted patients, a follow-up was completed to obtain the outcomes during 1 year.RESULTS:A total of 2015 patients with confirmed AF were included. AF was the primary diagnosis in 40.9% (n = 825) of them. 78.9% (n = 939) of the secondary AF diagnosis patients and 55.5% (n = 458) of the primary AF diagnosis patients were sustained AF. Compared with primary AF diagnosis group, the secondary AF diagnosis group was older with more comorbidities. At 1 year, the unadjusted mortality was much higher in the secondary AF diagnosis groups compared with the primary AF diagnosis groups. In Cox regression analysis with adjustment for confounding factors, patients with secondary AF diagnosis were associated with an increased mortality (relative risk 1.723; 95% CI: 1.283 to 2.315, p < .001). On multivariate analysis, age ≥ 75, LVSD, COPD, and diabetes were independent predictors of mortality in patients with primary AF diagnosis, while for the secondary AF diagnosis group, the risk factors were age ≥ 75, heart failure, and previous history of stroke.CONCLUSIONS:Patients presenting to ED with secondary diagnosis of AF were suffering from higher mortality risks compared with primary AF diagnosis patients. Physicians should distinguish these two groups in clinical practice.

Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy.

OBJECTIVE:To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs, as monotherapy or dual combination therapy, to improve daytime and nighttime BP control.METHODS:We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg; daytime mean BP < 135/85 mmHg; and nighttime mean BP < 120/70 mmHg), as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups.RESULTS:Patients' mean age was 71 years, and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy, and renin-angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52, P = 0.05 and OR = 0.41, P = 0.007, respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45, P = 0.004). Compared with RAS/diuretic therapy, BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27, P = 0.45).CONCLUSIONS:Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP, whereas diuretic-based therapies provided lower nighttime BP, compared with other antihypertensive regimens.

Impact of blood pressure lowering, cholesterol lowering and their combination in Asians and non-Asians in those without cardiovascular disease: an analysis of the HOPE 3 study.

BACKGROUND AND DESIGN:There are limited data on the effects of blood pressure and cholesterol lowering in Asians at intermediate risk and no cardiovascular disease. We report an analysis of the effects of blood pressure and cholesterol lowering in Asians enrolled in the Heart Outcomes Prevention Evaluation 3 (HOPE 3) trial.METHODS:We randomly assigned 6241 Asians and 6464 non-Asians at intermediate risk without cardiovascular disease to candesartan 16 mg/hydrochlorothiazide 12.5 mg or placebo and rosuvastatin 10 mg or placebo. The first co-primary outcome was a composite of cardiovascular disease death, myocardial infarction and stroke. The second co-primary outcome additionally included heart failure, cardiac arrest and revascularisation. Median follow-up was 5.6 years.RESULTS:Reduction in systolic blood pressure was less among Asians (4.3 vs. 7.7 mmHg for non-Asians, P < 0.0001) mainly due to a lesser effect in Chinese (2.1 mmHg) than in other Asians (7.3 mmHg), reduction in the latter being similar to non-Asians. The effect on the composite outcomes was similar, with no significant benefits from blood pressure lowering for either Asians (Chinese or non-Chinese) or non-Asians. Rosuvastatin reduced low-density lipoprotein cholesterol to a lesser degree in Asians (0.49 mmol/L (-19.1 mg/dL) compared with non-Asians 0.95 mmol/L (-36.7 mg/dL), Pinteraction < 0.0004). Yet both groups had similar reductions in the two co-primary outcomes. There was no increase in permanent medication discontinuation due to muscle-related symptoms in either group. There was an excess in new diabetes in non-Asians (4.70% rosuvastatin, 3.52% placebo, P = 0.025) but not in Asians (3.02% rosuvastatin, 4.04% placebo, P = 0.0342), Pinteraction = 0021.CONCLUSIONS:Candesartan/hydrochlorothiazide had fewer effects in reducing blood pressure in Chinese and rosuvastatin reduced low-density lipoprotein cholesterol to a lesser extent in Asians compared with non-Asians. There was no overall reduction in clinical events with lowering blood pressure in either Asians or non-Asians, whereas there were clear and consistent benefits with lipid lowering in both. Despite extensive analyses, we have no obvious explanation for the observed findings. Future studies need to include larger numbers of individuals from different regions of the world to ensure that the results of trials are applicable globally.

Comments on 2018 ESC/ESH Hypertension Guidelines: Chinese Perspective.

A randomized unblinded trial to compare effects of intensive versus conventional lipid-lowering therapy in patients undergoing renal artery stenting.

BACKGROUND:Although current guidelines recommend the use of statins for severe atherosclerotic renal artery stenosis (ARAS), the renal protection of intensive lipid-lowering therapy in patients with ARAS who underwent stent placement remains uncertain. The aim of this study was to compare the renal-protective effect of intensive lipid lowering with that of conventional lipid lowering in patients with ARAS undergoing stent placement.METHODS:A total 150 patients with severe ARAS undergoing stent placement were randomly (1:1) assigned to receive intensive lipid lowering [target low-density lipoprotein cholesterol (LDL-C) <70mg/dL] or conventional lipid lowering (target LDL-C ≥70mg/dL, <128mg/dL). All patients received rosuvastatin. We adjusted LDL-C to the goal within two months after renal stenting and maintained stability. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) at 12 months.RESULTS:During the study period, LDL-C was lower in the patients with intensive lipid lowering than with conventional lipid lowering (at 12 months 58.0±11.6 vs 85.1±15.5mg/dL, p<0.001). At 12-month follow-up, eGFR (91.8±30.2 vs 78.5±19.5)mL/min·1.73m2, p=0.002) and the increase in eGFR compared to baseline [14.8(IQR, 4.1, 26.7) vs -0.4(IQR, -9.5, 8.0)mL/min·1.73m2, p<0.001] were higher in the patients with intensive lipid lowering than with conventional lipid lowering. Urinary albumin-creatinine ratio [42.2(IQR, 20.0, 60.9) vs 60.8(IQR, 26.8, 121.6)mg/g, p=0.032] was lower and the decrease in urinary albumin-creatinine ratio compared to baseline [27.4(IQR, 3.0, 53.8) vs -3.1(IQR, -17.3, 30.9)mg/g, p=0.001] was higher in the patients with intensive lipid lowering than with conventional lipid lowering. The restenosis rate (3.1% vs 3.4%, p=0.711) and major clinical events (6.8% vs 11.0%, p=0.37) were similar between the two groups.CONCLUSIONS:In patients with severe ARAS undergoing stent placement, intensive lipid lowering showed significant benefits in renal protection over conventional lipid-lowering therapy.

The association of grip strength with cardiovascular diseases and all-cause mortality in people with hypertension: Findings from the Prospective Urban Rural Epidemiology China Study.

BACKGROUND:Both hypertension and grip strength (GS) are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to affect CVD and all-cause mortality is unknown. This study sought to investigate the associations of GS with the risk of major CVD incidence, CVD mortality, and all-cause mortality in patients with hypertension.METHODS:GS was measured using a Jamar dynamometer (Sammons Preston, Bolingbrook, IL, USA) in participants aged 35-70 years from 12 provinces included in the Prospective Urban Rural Epidemiology China Study. Cox frailty proportional hazards models were used to examine the associations of GS and hypertension and the outcomes of all-cause mortality and CVD incidence/mortality.RESULTS:Among 39,862 participants included in this study, 15,964 reported having hypertension, and 9095 had high GS at baseline. After a median follow-up of 8.9 years (interquartile range, 6.7-9.9 years), 1822 participants developed major CVD, and 1250 deaths occurred (388 as a result of CVD). Compared with normotensive participants with high GS, hypertensive patients with high GS had a higher risk of major CVD incidence (hazard ratio (HR) = 2.39; 95% confidence interval (95%CI): 1.86-3.06; p < 0.001) or CVD mortality (HR = 3.11; 95%CI: 1.59-6.06; p < 0.001) but did not have a significantly increased risk of all-cause mortality (HR = 1.24; 95%CI: 0.92-1.68; p = 0.159). These risks were further increased if hypertensive participants whose GS level was low (major CVD incidence, HR = 3.31, 95%CI: 2.60-4.22, p < 0.001; CVD mortality, HR = 4.99, 95%CI: 2.64-9.43, p < 0.001; and all-cause mortality, HR = 1.93, 95%CI: 1.47-2.53, p < 0.001).CONCLUSION:The present study demonstrates that low GS is associated with the highest risk of major CVD incidence, CVD mortality, and all-cause mortality among hypertensive patients. High levels of GS appear to mitigate long-term mortality risk among hypertensive patients.

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants.

AIMS:Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated.METHODS AND RESULTS:After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years.CONCLUSION:The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.TRIAL REGISTRATION NUMBER:NCT00468923.

Efficacy and safety of rivaroxaban plus aspirin in women and men with chronic coronary or peripheral artery disease.

AIMS:The COMPASS trial demonstrated that the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease or peripheral artery disease by 24% during a mean follow-up of 23 months. We explored whether this effect varies by sex.METHODS AND RESULTS:The effects were examined in women and men using log-rank tests and Kaplan-Meier curve. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were obtained from stratified Cox proportional hazards models to explore subgroup effects including subgroup of women and men according to baseline modified REACH risk score. Of 27 395 patients randomized, 18 278 were allocated to receive rivaroxaban plus aspirin (n = 9152) or aspirin alone (n = 9126), and of these, 22.1% were women. Women compared with men had similar incidence rates for MACE and major bleeding but borderline lower rates for myocardial infarction (1.7% vs. 2.2%, P = 0.05). The effect of combination therapy compared with aspirin in women and men was consistent for MACE (women: 3.8% vs. 5.2%, HR 0.72, 95% CI 0.54-0.97; men: 4.2% vs. 5.5%, HR 0.76, 95% CI 0.66-0.89; P interaction 0.75) and major bleeding (women: 3.1% vs. 1.4%, HR 2.22, 95% CI 1.42-3.46; men: 3.2% vs. 2.0%, HR 1.60, 95% CI 1.29-1.97; P interaction 0.19). There was no significant interaction between randomized treatment and baseline modified REACH score above or below the median for MACE or major bleeding.CONCLUSION:In patients with stable coronary artery disease or peripheral artery disease, the combination of rivaroxaban (2.5 mg twice daily) and aspirin compared with aspirin alone appears to produce consistent benefits in women and men, independent of baseline cardiovascular risk.

Fruit, vegetable, and legume intake and the risk of all-cause, cardiovascular, and cancer mortality: A prospective study.

BACKGROUND & AIMS:Although fruits and vegetable consumption has been shown to be associated with lower risks of mortality, cancers, and cardiovascular disease (CVD), there are limited data from China on the shape of the association. This study aimed to quantify the relationship between levels of fruit, vegetable, and legume consumption with the risk of major CVD, CVD mortality, cancer incidence, cancer mortality, and all-cause mortality.METHODS:In the baseline survey, participants attended 1 of 115 (45 urban and 70 rural) communities from 12 provinces to complete a standardized questionnaire, and undergo a physical examination between 2005 and 2009, and were followed up till 2017 (for the current analysis). Diet was assessed through in-person interviews by using validated food-frequency questionnaires. The clinical outcomes were adjudicated centrally by trained physicians using standardized definitions. Cox frailty models were used to explore the associations between fruit, vegetable, and legume consumption with the risk of all-cause, CVD, and cancer mortality.RESULTS:A total of 41 243 participants were eligible for inclusion in the analyses. The average combined average daily intake of fruit, vegetable, and legume was 2.97 [standard deviation (SD) 1.22] servings per day. During a median follow-up of 8.9 years [interquartile range (IQR) 6.7-9.9 years], we recorded 1893 major CVDs, 794 cancer events, and 1324 deaths, with 411 CVD deaths and 429 cancer deaths. In the models adjusted for age, sex, and center (random effect), a higher total intake of fruit, vegetable, and legume was inversely associated with CVD mortality, cancer incidence, cancer mortality, and all-cause mortality. After adjusting for additional covariates, the associations were evidently attenuated and only the association with all-cause mortality (hazard ratio [HR] trend 0.92, 95% CI 0.86-0.98, p trend = 0.021) remained significant, with a non-significant trend for major CVD (HR trend 1.02, 95% CI 0.97-1.08, p trend = 0.449), CVD mortality (HR trend 0.94, 95% CI 0.84-1.06, p trend = 0.301), cancer incidence (HR trend 0.97, 95% CI 0.89-1.06, p trend = 0.540), or cancer mortality (HR trend 0.92, 95% CI 0.82-1.04, p trend = 0.174). Compared with the reference group, the risk of all-cause mortality was the lowest for four to five servings of total daily intake of fruit, vegetable, and legume (HR 0.73, 95% CI 0.55-0.97), and did not show a further decrease for the higher intake group. Separately, fruit intake was associated with a lower risk of all-cause mortality (HR trend 0.92, 95% CI 0.86-0.99, p trend = 0.020) and legume intake was associated with a lower risk of major CVD (HR trend 0.95, 95% CI 0.90-0.99, p trend = 0.028) and all-cause mortality (HR trend 0.94, 95% CI 0.89-0.99, p trend = 0.020) in the fully adjusted models.CONCLUSIONS:This prospective study suggests that Chinese people with daily consumption of four to five servings (equivalent to 500-625 g/day) of fruit, vegetable, and legume demonstrated the lowest mortality, which conveys an encouraging message to the public that lifestyle modification to increase fruit, vegetable, and legume intakes may have greater beneficial effects on reducing all-cause mortality.

Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline: The COMPASS MRI Substudy.

BACKGROUND AND PURPOSE:Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities.METHODS:Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities.RESULTS:At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests.CONCLUSIONS:Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Increased mortality in patients with secondary diagnosis of atrial fibrillation: Report from Chinese AF registry.

BACKGROUND:The relationship between mortality and the primary diagnosis in AF patients is poorly recognized. The purpose of the study is to compare the differences on mortality in patients with a primary or secondary diagnosis of AF and to identify risk factors amenable to treatment.METHODS:This was a prospective cohort study using data from the Chinese AF registry. For admitted patients, a follow-up was completed to obtain the outcomes during 1 year.RESULTS:A total of 2015 patients with confirmed AF were included. AF was the primary diagnosis in 40.9% (n = 825) of them. 78.9% (n = 939) of the secondary AF diagnosis patients and 55.5% (n = 458) of the primary AF diagnosis patients were sustained AF. Compared with primary AF diagnosis group, the secondary AF diagnosis group was older with more comorbidities. At 1 year, the unadjusted mortality was much higher in the secondary AF diagnosis groups compared with the primary AF diagnosis groups. In Cox regression analysis with adjustment for confounding factors, patients with secondary AF diagnosis were associated with an increased mortality (relative risk 1.723; 95% CI: 1.283 to 2.315, p < .001). On multivariate analysis, age ≥ 75, LVSD, COPD, and diabetes were independent predictors of mortality in patients with primary AF diagnosis, while for the secondary AF diagnosis group, the risk factors were age ≥ 75, heart failure, and previous history of stroke.CONCLUSIONS:Patients presenting to ED with secondary diagnosis of AF were suffering from higher mortality risks compared with primary AF diagnosis patients. Physicians should distinguish these two groups in clinical practice.

Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy.

OBJECTIVE:To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs, as monotherapy or dual combination therapy, to improve daytime and nighttime BP control.METHODS:We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg; daytime mean BP < 135/85 mmHg; and nighttime mean BP < 120/70 mmHg), as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups.RESULTS:Patients' mean age was 71 years, and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy, and renin-angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52, P = 0.05 and OR = 0.41, P = 0.007, respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45, P = 0.004). Compared with RAS/diuretic therapy, BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27, P = 0.45).CONCLUSIONS:Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP, whereas diuretic-based therapies provided lower nighttime BP, compared with other antihypertensive regimens.

Impact of blood pressure lowering, cholesterol lowering and their combination in Asians and non-Asians in those without cardiovascular disease: an analysis of the HOPE 3 study.

BACKGROUND AND DESIGN:There are limited data on the effects of blood pressure and cholesterol lowering in Asians at intermediate risk and no cardiovascular disease. We report an analysis of the effects of blood pressure and cholesterol lowering in Asians enrolled in the Heart Outcomes Prevention Evaluation 3 (HOPE 3) trial.METHODS:We randomly assigned 6241 Asians and 6464 non-Asians at intermediate risk without cardiovascular disease to candesartan 16 mg/hydrochlorothiazide 12.5 mg or placebo and rosuvastatin 10 mg or placebo. The first co-primary outcome was a composite of cardiovascular disease death, myocardial infarction and stroke. The second co-primary outcome additionally included heart failure, cardiac arrest and revascularisation. Median follow-up was 5.6 years.RESULTS:Reduction in systolic blood pressure was less among Asians (4.3 vs. 7.7 mmHg for non-Asians, P < 0.0001) mainly due to a lesser effect in Chinese (2.1 mmHg) than in other Asians (7.3 mmHg), reduction in the latter being similar to non-Asians. The effect on the composite outcomes was similar, with no significant benefits from blood pressure lowering for either Asians (Chinese or non-Chinese) or non-Asians. Rosuvastatin reduced low-density lipoprotein cholesterol to a lesser degree in Asians (0.49 mmol/L (-19.1 mg/dL) compared with non-Asians 0.95 mmol/L (-36.7 mg/dL), Pinteraction < 0.0004). Yet both groups had similar reductions in the two co-primary outcomes. There was no increase in permanent medication discontinuation due to muscle-related symptoms in either group. There was an excess in new diabetes in non-Asians (4.70% rosuvastatin, 3.52% placebo, P = 0.025) but not in Asians (3.02% rosuvastatin, 4.04% placebo, P = 0.0342), Pinteraction = 0021.CONCLUSIONS:Candesartan/hydrochlorothiazide had fewer effects in reducing blood pressure in Chinese and rosuvastatin reduced low-density lipoprotein cholesterol to a lesser extent in Asians compared with non-Asians. There was no overall reduction in clinical events with lowering blood pressure in either Asians or non-Asians, whereas there were clear and consistent benefits with lipid lowering in both. Despite extensive analyses, we have no obvious explanation for the observed findings. Future studies need to include larger numbers of individuals from different regions of the world to ensure that the results of trials are applicable globally.

Comments on 2018 ESC/ESH Hypertension Guidelines: Chinese Perspective.

A randomized unblinded trial to compare effects of intensive versus conventional lipid-lowering therapy in patients undergoing renal artery stenting.

BACKGROUND:Although current guidelines recommend the use of statins for severe atherosclerotic renal artery stenosis (ARAS), the renal protection of intensive lipid-lowering therapy in patients with ARAS who underwent stent placement remains uncertain. The aim of this study was to compare the renal-protective effect of intensive lipid lowering with that of conventional lipid lowering in patients with ARAS undergoing stent placement.METHODS:A total 150 patients with severe ARAS undergoing stent placement were randomly (1:1) assigned to receive intensive lipid lowering [target low-density lipoprotein cholesterol (LDL-C) <70mg/dL] or conventional lipid lowering (target LDL-C ≥70mg/dL, <128mg/dL). All patients received rosuvastatin. We adjusted LDL-C to the goal within two months after renal stenting and maintained stability. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) at 12 months.RESULTS:During the study period, LDL-C was lower in the patients with intensive lipid lowering than with conventional lipid lowering (at 12 months 58.0±11.6 vs 85.1±15.5mg/dL, p<0.001). At 12-month follow-up, eGFR (91.8±30.2 vs 78.5±19.5)mL/min·1.73m2, p=0.002) and the increase in eGFR compared to baseline [14.8(IQR, 4.1, 26.7) vs -0.4(IQR, -9.5, 8.0)mL/min·1.73m2, p<0.001] were higher in the patients with intensive lipid lowering than with conventional lipid lowering. Urinary albumin-creatinine ratio [42.2(IQR, 20.0, 60.9) vs 60.8(IQR, 26.8, 121.6)mg/g, p=0.032] was lower and the decrease in urinary albumin-creatinine ratio compared to baseline [27.4(IQR, 3.0, 53.8) vs -3.1(IQR, -17.3, 30.9)mg/g, p=0.001] was higher in the patients with intensive lipid lowering than with conventional lipid lowering. The restenosis rate (3.1% vs 3.4%, p=0.711) and major clinical events (6.8% vs 11.0%, p=0.37) were similar between the two groups.CONCLUSIONS:In patients with severe ARAS undergoing stent placement, intensive lipid lowering showed significant benefits in renal protection over conventional lipid-lowering therapy.