Relationships between components of blood pressure and cardiovascular events in patients with stable coronary artery disease and hypertension

Observational studies have shown a J-shaped relationship between diastolic blood pressure (BP) and cardiovascular events in hypertensive patients with coronary artery disease. We investigated whether the increased risk associated with low diastolic BP reflects elevated pulse pressure (PP). In 22 672 hypertensive patients with coronary artery disease from the CLARIFY registry (Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease), followed for a median of 5.0 years, BP was measured annually and averaged. The relationships between PP and diastolic BP, alone or combined, and the primary composite outcome (cardiovascular death or myocardial infarction) were analyzed using multivariable Cox proportional hazards models. Adjusted hazard ratios for the primary outcome were 1.62 (95% confidence interval [CI], 1.40–1.87), 1.00 (ref), 1.07 (95% CI, 0.94–1.21), 1.54 (95% CI, 1.32–1.79), and 2.34 (95% CI, 1.95–2.81) for PP<45, 45 to 54 (reference), 55 to 64, 65 to 74, and ≥75 mm Hg, respectively, and 1.50 (95% CI, 1.31–1.72), 1.00 (reference), and 1.58 (95% CI, 1.42–1.77) for diastolic BPs of <70, 70 to 79 (ref), and ≥80 mm Hg, respectively. In a cross-classification analysis between diastolic BP and PP, the relationship between diastolic BP and the primary outcome remained J-shaped when the analysis was restricted to patients with the lowest-risk PP (45–64 mm Hg), with adjusted hazard ratios of 1.53 (95% CI, 1.27–1.83), 1.00 (ref), and 1.54 (95% CI, 1.34–1.75) in the <70, 70 to 79 (reference), and ≥80 mm Hg subgroups, respectively. The J-shaped relationship between diastolic BP and cardiovascular events in hypertensive patients with coronary artery disease persists in patients within the lowest-risk PP range and is therefore unlikely to be solely the consequence of an increased PP reflecting advanced vascular disease

Motor sequence learning in children with recovered and persistent developmental stuttering: preliminary findings

PURPOSE: Previous studies have associated developmental stuttering with difficulty learning new motor skills. We investigated non-speech motor sequence learning in children with persistent developmental stuttering (CWS), children who have recovered from developmental stuttering (CRS) and typically developing controls (CON). METHODS: Over the course of two days, participants completed the Multi-Finger Sequencing Task, consisting of repeated trials of a10-element sequence, interspersed with trials of random sequences of the same length. We evaluated motor sequence learning using accuracy and response synchrony, a timing measure for evaluation of sequencing timing. We examined error types as well as recognition and recall of the repeated sequences. RESULTS: CWS demonstrated lower performance accuracy than CON and CRS on the first day of the finger tapping experiment but improved to the performance level of CON and CRS on the second day. Response synchrony showed no overall difference among CWS, CRS and CON. Learning scores of repeated sequences did not differ from learning scores of random sequences in CWS, CRS and CON. CON and CRS demonstrated an adaptive strategy to response errors, whereas CWS maintained a high percentage of corrected errors for both days. CONCLUSIONS: Our study examined non-speech sequence learning across CWS, CRS and CON. Our preliminary findings support the idea that developmental stuttering is not associated with sequence learning per se but rather with general fine motor performance difficulties

Prevalence of anginal symptoms and myocardial ischemia and their effect on clinical outcomes in outpatients with stable coronary artery disease: data from the international observational CLARIFY registry

Importance: In the era of widespread revascularization and effective antianginals, the prevalence and prognostic effect of anginal symptoms and myocardial ischemia among patients with stable coronary artery disease (CAD) are unknown.<p></p> Objective: To describe the current clinical patterns among patients with stable CAD and the association of anginal symptoms or myocardial ischemia with clinical outcomes.<p></p> Design, Setting, and Participants: The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled outpatients in 45 countries with stable CAD in 2009 to 2010 with 2-year follow-up (median, 24.1 months; range, 1 day to 3 years). Enrollees included 32 105 outpatients with prior myocardial infarction, chest pain, and evidence of myocardial ischemia, evidence of CAD on angiography, or prior revascularization. Of these, 20 291 (63.2%) had undergone a noninvasive test for myocardial ischemia within 12 months of enrollment and were categorized into one of the following 4 groups: no angina or ischemia (n = 13 207 [65.1%]); evidence of myocardial ischemia without angina (silent ischemia) (n = 3028 [14.9%]); anginal symptoms alone (n = 1842 [9.1%]); and angina and ischemia (n = 2214 [10.9%]).<p></p> Exposures: Stable CAD.<p></p> Main Outcome and Measure: The composite of cardiovascular (CV)–related death or nonfatal myocardial infarction.<p></p> Results: Overall, 4056 patients (20.0%) had anginal symptoms and 5242 (25.8%) had evidence of myocardial ischemia on results of noninvasive testing. Of 469 CV-related deaths or myocardial infarctions, 58.2% occurred in patients without angina or ischemia, 12.4% in patients with ischemia alone, 12.2% in patients with angina alone, and 17.3% in patients with both. The hazard ratios for the primary outcome relative to patients without angina or ischemia and adjusted for age, sex, geographic region, smoking status, hypertension, diabetes mellitus, and dyslipidemia were 0.90 (95% CI, 0.68-1.20; P = .47) for ischemia alone, 1.45 (95% CI, 1.08-1.95; P = .01) for angina alone, and 1.75 (95% CI, 1.34-2.29; P <.001) for both. Similar findings were observed for CV-related death and for fatal or nonfatal myocardial infarction.<p></p> Conclusions and Relevance: In outpatients with stable CAD, anginal symptoms (with or without ischemia on noninvasive testing) but not silent ischemia appear to be associated with an increased risk for adverse CV outcomes. Most CV events occurred in patients without angina or ischemia

Gender- and age-related differences in clinical presentation and management of outpatients with stable coronary artery disease

<br>Introduction: Contemporary generalizable data on the demographics and management of outpatients with stable coronary artery disease (CAD) in routine clinical practice are sparse. Using the data from the CLARIFY registry we describe gender- and age-related differences in baseline characteristics and management of these patients across broad geographic regions.</br> <br>Methods: This international, prospective, observational, longitudinal registry enrolled stable CAD outpatients from 45 countries in Africa, Asia, Australia, Europe, the Middle East, and North, Central, and South America.</br> <br>Results: Baseline data were available for 33 280 patients. Mean (SD) age was 64 (10.5) years and 22.5% of patients were female. The prevalence of CAD risk factors was generally higher in women than in men. Women were older (66.6 vs 63.4 years), more frequently diagnosed with diabetes (33% vs 28%), hypertension (79% vs 69%), and higher resting heart rate (69 vs 67 bpm), and were less physically active. Smoking and a history of myocardial infarction were more common in men. Women were more likely to have angina (28% vs 20%), but less likely to have undergone revascularization procedures. CAD was more likely to be asymptomatic in older patients perhaps because of reduced levels of physical activity. Prescription of evidence-based medication for secondary prevention varied with age, with patients ≥ 75 years treated less often with beta blockers, aspirin and angiotensin-converting enzyme inhibitors than patients < 65 years.</br> <br>Conclusions: Important gender-related differences in clinical characteristics and management continue to exist in all age groups of outpatients with stable CAD.</br&gt

Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease

Aims: Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the ‘smoker’s paradox’ suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease. Methods: The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers. Results: Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p < 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p < 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p < 0.05). Conclusion: In contrast to the ‘smoker’s paradox’, current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564)

Potential impact of the 2017 ACC/AHA guideline on high blood pressure in normotensive patients with stable coronary artery disease: insights from the CLARIFY registry

Aims: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline on high blood pressure (BP) lowered the threshold defining hypertension and BP target in high-risk patients to 130/80 mmHg. Patients with coronary artery disease and systolic BP 130-139 mmHg or diastolic BP 80-89 mmHg should now receive medication to achieve this target. We aimed to investigate the relationship between BP and cardiovascular events in 'real-life' patients with coronary artery disease considered as having normal BP until the recent guideline. Methods and results: Data from 5956 patients with stable coronary artery disease, no history of hypertension or heart failure, and average BP <140/90 mmHg, enrolled in the CLARIFY registry (November 2009 to June 2010), were analysed. In a multivariable-adjusted Cox proportional hazards model, after a median follow-up of 5.0 years, diastolic BP 80-89 mmHg, but not systolic BP 130-139 mmHg, was associated with increased risk of the primary endpoint, a composite of cardiovascular death, myocardial infarction, or stroke (hazard ratio 2.15, 95% confidence interval 1.22-3.81 vs. 70-79 mmHg and 1.12, 0.64-1.97 vs. 120-129 mmHg). No significant increase in risk for the primary endpoint was observed for systolic BP <120 mmHg or diastolic BP <70 mmHg. Conclusion: In patients with stable coronary artery disease defined as having normal BP according to the 140/90 mmHg threshold, diastolic BP 80-89 mmHg was associated with increased cardiovascular risk, whereas systolic BP 130-139 mmHg was not, supporting the lower diastolic but not the lower systolic BP hypertension-defining threshold and treatment target in coronary artery disease. ClinicalTrials identifier: ISRCTN43070564

B-blockers, calcium antagonists, and mortality in stable coronary artery disease: An international cohort study

Aims: The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain. Methods and results We analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009–2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84–1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79–1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91–1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50–0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37–0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52–0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality. Conclusion In this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI