Summary Background Studies have challenged the appropriateness of accepted blood pressure targets. We hypothesised that different levels of low blood pressure are associated with benefit for some, ...but harm for other outcomes. Methods In this analysis, we assessed the previously reported outcome data from high-risk patients aged 55 years or older with a history of cardiovascular disease, 70% of whom had hypertension, from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination, with a median follow-up of 56 months. Detailed descriptions of randomisation and intervention have already been reported. We analysed the associations between mean blood pressure achieved on treatment; prerandomisation baseline blood pressure; or time-updated blood pressure (last on treatment value before an event) on the composite outcome of cardiovascular death, myocardial infarction, stroke, and hospital admission for heart failure; the components of the composite outcome; and all-cause death. Analysis was done by Cox regression analysis, ANOVA, and χ2 . These trials were registered with ClinicalTrials.gov , number NCT00153101. Findings Recruitment for ONTARGET took place between Dec 1, 2001, and July 31, 2008. TRANSCEND took place between Nov 1, 2001, and May 30, 2004. 30 937 patients were recruited from 733 centres in 40 countries and followed up for a median of 56 months. In ONTARGET, 25 127 patients known to be tolerant to angiotensin-converting-enzyme (ACE)-inhibitors were randomly assigned after a run-in period to oral ramipril 10 mg/day (n=8407), telmisartan 80 mg/day (n=8386), or the combination of both (n=8334). In TRANSCEND, 5810 patients who were intolerant to ACE-inhibitors were randomly assigned to oral telmisartan 80 mg/day (n=2903) or placebo (n=2907). Baseline systolic blood pressure (SBP) 140 mm Hg or higher was associated with greater incidence of all outcomes compared with 120 mm Hg to less than 140 mm Hg. By contrast, a baseline diastolic blood pressure (DBP) less than 70 mm Hg was associated with the highest risk for most outcomes compared with all DBP categories 70 mm Hg or more. In 4052 patients with SBP less than 120 mm Hg on treatment, the risk of the composite cardiovascular outcome (adjusted hazard ratio HR 1·14, 95% CI 1·03–1·26), cardiovascular death (1·29, 1·12–1·49), and all deaths (1·28, 1·15–1·42) were increased compared with those in whom SBP was 120–140 mm Hg during treatment (HR 1 for all outcomes, n=16099). No harm or benefit was observed for myocardial infarction, stroke, or hospital admission for heart failure. Mean achieved SBP more accurately predicted outcomes than baseline or time-updated SBP, and was associated with the lowest risk at approximately 130 mm Hg, and at 110–120 mm Hg risk increased for the combined outcome, cardiovascular death, and all-cause death except stroke. A mean DBP less than 70 mm Hg (n=5352) during treatment was associated with greater risk of the composite primary outcome (HR 1·31, 95% CI 1·20–1·42), myocardial infarction (1·55, 1·33–1·80), hospital admission for heart failure (1·59, 1·36–1·86) and all-cause death (1·16, 1·06–1·28) than a DBP 70–80 mm Hg (14 305). A pretreatment and mean on-treatment DBP of about 75 mm Hg was associated with the lowest risk. Interpretation Mean achieved SBP less than 120 mm Hg during treatment was associated with increased risk of cardiovascular outcomes except for myocardial infarction and stroke. Similar patterns were observed for DBP less than 70 mm Hg, plus increased risk for myocardial infarction and hospital admission for heart failure. Very low blood pressure achieved on treatment was associated with increased risks of several cardiovascular disease events. These data suggest that the lowest blood pressure possible is not necessarily the optimal target for high-risk patients, although it is not possible to rule out some effect of reverse causality. Funding Boehringer Ingelheim.
The 2021 guidelines primary panel selected clinically relevant questions and produced updated recommendations, on the basis of important new findings that have emerged since the 2016 guidelines. In ...patients with clinical atherosclerosis, abdominal aortic aneurysm, most patients with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy continues to be recommended. We have introduced the concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with nonstatin agents, and have identified the secondary prevention patients who have been shown to derive the largest benefit from intensification of therapy with these agents. For all other patients, we emphasize risk assessment linked to lipid/lipoprotein evaluation to optimize clinical decision-making. Lipoprotein(a) measurement is now recommended once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. For any patient with triglycerides ˃ 1.5 mmol/L, either non-high-density lipoprotein cholesterol or apolipoprotein B are the preferred lipid parameter for screening, rather than low-density lipoprotein cholesterol. We provide updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. There are new recommendations on the preventative care of women with hypertensive disorders of pregnancy. Health behaviour modification, including regular exercise and a heart-healthy diet, remain the cornerstone of cardiovascular disease prevention. These guidelines are intended to provide a platform for meaningful conversation and shared-decision making between patient and care provider, so that individual decisions can be made for risk screening, assessment, and treatment.
Le panel principal responsable des lignes directrices 2021 a sélectionné des éléments cliniquement pertinents et a soumis des recommandations actualisées, basées sur de nouvelles découvertes d'importance apparues depuis les lignes directrices de 2016. Ainsi, le traitement par statine reste recommandé pour les patients atteints d'athérosclérose clinique, d'anévrisme de l'aorte abdominale, pour la plupart des patients diabétiques ou atteints d'insuffisance rénale chronique, et chez ceux dont le cholestérol à lipoprotéines de basse densité est ≥ 5 mmol/l. Nous avons introduit la notion de seuils pour le traitement des lipides/lipoprotéines afin d'intensifier le traitement hypolipidémiant avec des agents non-statiniques, et nous avons identifié les patients en prévention secondaire distingués comme ayant tirer le plus grand bénéfice de l'intensification du traitement avec ces agents. Pour tous les autres patients, nous mettons l'accent sur l'appréciation du risque par le biais de l'évaluation des lipides/lipoprotéines afin d'optimiser la prise de décision clinique. Le dosage de la lipoprotéine (a) est maintenant recommandé une fois dans la vie d'un patient, dans le cadre du dépistage initial des lipides pour évaluer le risque cardiovasculaire. Pour tout patient présentant des taux de triglycérides ˃ 1,5 mmol/l, l'apolipoprotéine B ou le cholestérol lié aux lipoprotéines autres que celles de haute densité sont les indices lipidiques à privilégier pour le dépistage, plutôt que le cholestérol à lipoprotéines de basse densité. Nous proposons des recommandations actualisées concernant le rôle du score calcique des artères coronaires en tant qu'outil de décision clinique pour aider à la décision d'administrer un traitement par statine. Il existe de nouvelles recommandations concernant les soins préventifs des femmes souffrant de troubles hypertensifs de la grossesse. Le changement de comportement en matière de santé, incluant l'exercice physique régulier et une alimentation saine pour le coeur, reste la pierre angulaire de la prévention des maladies cardiovasculaires. Ces lignes directrices visent à fournir une plateforme pour une discussion constructive et une prise de décision partagée entre le patient et le prestataire de soins, afin que des décisions individuelles puissent être prises pour le dépistage, l'évaluation et le traitement des risques.
To clarify the major features of the apical ballooning syndrome, we performed a systematic review of the existing literature.
Review of all relevant case series using the MEDLINE and EMBASE databases ...resulted in the identification of 14 studies. These studies suggest that the apical ballooning syndrome accounts for approximately 2.0% of ST-segment elevation infarcts, with most cases described in post-menopausal women. The most common clinical presentations are chest pain and dyspnoea, reported in 67.8 and 17.8% of the patients, respectively. Cardiogenic shock (4.2% of the patients) and ventricular fibrillation (1.5%) were not infrequent. ST-segment elevation was reported in 81.6% of the patients, T wave abnormalities in 64.3%, and Q waves in 31.8%. Cardiac biomarkers were usually mildly elevated, as reported in 86.2% of the patients. Typically, patients had left ventricular (LV) dysfunction on admission, with mean ejection fraction ranging from 20 to 49%. However, over a period of days to weeks, all patients experienced dramatic improvement in LV function. The onset of symptoms was often preceded by emotional (26.8%) or physical stress (37.8%). Norepinephrine concentration was elevated in 74.3% of the patients. Prognosis was generally excellent, with full recovery in most patients. In-hospital mortality was 1.1%. Only 3.5% of the patients experienced a recurrence.
Clinicians should consider this syndrome in the differential diagnosis of patients presenting with chest pain, especially in post-menopausal women with a recent history of emotional or physical stress.
Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events ...substantially.
In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval CI, 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of ...endothelial function and other vascular markers in apparently healthy men.
The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24).
In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.
Abstract
Aims
Current guidelines of hypertensive management recommend upper limits for systolic (SBP) and diastolic blood pressure (DBP). J-curve associations of BP with risk exist for some outcomes ...suggesting that lower limits of DBP goals may also apply. We examined the association between mean attained DBP and cardiovascular (CV) outcomes in patients who achieved an on-treatment SBP in the range of 120 to <140 mmHg in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND) trials on patients with high CV risk. This SBP range was associated with the lowest CV risk.
Methods
We analysed the outcome data from patients age 55 years or older with CV disease from the ONTARGET and TRANSCEND trials that randomized high-risk patients to ramipril, telmisartan, and the combination. In patients with controlled SBP (on-treatment 120 to <140 mmHg), the composite outcome of CV death, myocardial infarction, stroke and hospital admission for heart failure, the components thereof, and all-cause mortality were analysed according to mean on-treatment DBP as categorical (<70, 70 to <80, 80 to <90, and ≥90 mmHg) and continuous variable as well as the change of DBP according to baseline DBP. Pulse pressure (PP) was related to outcomes as a continuous variable.
Results
In 16 099 of 31 546 patients, mean achieved SBP was 120 to <140 mmHg. The nominally lowest risk for all outcomes was observed at an achieved DBP of 70 to <80 mmHg. A higher achieved DBP was associated with a higher risk for the outcomes of stroke and of hospitalization for heart failure (≥80 mmHg) and myocardial infarction (≥90 mmHg). A lower achieved DBP (<70 mmHg) was associated with a higher risk for the primary outcome hazard ratio (HR) 1.29, 95% confidence interval (95% CI) 1.15–1.45; P < 0.0001, myocardial infarction HR 1.54 (95% CI 1.26–1.88, P < 0.0001) and hospitalization for heart failure HR 1.81 (95% CI 1.47–2.24, P < 0.0001) and all-cause death (HR 1.19, 95% CI 1.04–1.35; P < 0.0001) while there was no signal for stroke and CV death compared to DBP 70 to <80 mmHg. A decrease of DBP was associated with lower risk when baseline DBP was >80 mmHg. The associations to outcomes were similar when patients were divided to SBP 120 to <130 mmHg or 130 to <140 mmHg for DBP or PP.
Conclusion
Compared to a DBP of 70 to <80 mmHg, lower and higher DBP was associated with a higher risk in patients achieving a SBP of 120 to <140 mmHg. Associations of DBP and PP to risk were similar notably at controlled SBP. These data suggest at optimal achieved SBP, risk is still defined by low or high DBP. These findings support guidelines which take DBP at optimal SBP control into consideration.
Abstract
Aims
Resting heart rate (RHR) has been shown to be associated with cardiovascular outcomes in various conditions. It is unknown whether different levels of RHR and different associations ...with cardiovascular outcomes occur in patients with or without diabetes, because the impact of autonomic neuropathy on vascular vulnerability might be stronger in diabetes.
Methods and results
We examined 30 937 patients aged 55 years or older with a history of or at high risk for cardiovascular disease and after myocardial infarction, stroke, or with proven peripheral vascular disease from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination followed for a median of 56 months. We analysed the association of mean achieved RHR on-treatment with the primary composite outcome of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, the components of the composite primary outcome, and all-cause death as continuous and categorical variables. Data were analysed by Cox regression analysis, ANOVA, and χ2 test. These trials were registered with ClinicalTrials.gov.number NCT00153101. Patients were recruited from 733 centres in 40 countries between 1 December 2001 and 31 July 2008 (ONTARGET) and 1 November 2001 until 30 May 2004 (TRANSCEND). In total, 19 450 patients without diabetes and 11 487 patients with diabetes were stratified by mean RHR. Patients with diabetes compared to no diabetes had higher RHRs (71.8 ± 9.0 vs. 67.9 ± 8.8, P < 0.0001). In the categories of <60 bpm, 60 ≤ 65 bpm, 65 ≤ 70 bpm, 70 ≤ 75 bpm, 75 ≤ 80 bpm and ≥80 bpm, non-diabetic patients had an increased hazard of the primary outcome with mean RHR of 75 ≤ 80 bpm (adjusted hazard ratio HR 1.17 (1.01–1.36)) compared to RHR 60 ≤ 65 bpm. For patients with in-trial RHR ≥80 bpm the hazard ratios were highest (diabetes: 1.96 (1.64–2.34), no diabetes: 1.73 (1.49–2.00), For cardiovascular death hazards were also clearly increased at RHR ≥80 bpm (diabetes 1.99, (1.53–2.58), no diabetes 1.73 (1.38–2.16). Similar results were obtained for hospitalization for heart failure and all-cause death while the effect of RHR on myocardial infarction and stroke was less pronounced. Results were robust after adjusting for various risk indicators including beta-blocker use and atrial fibrillation. No significant association to harm was observed at lower RHR.
Conclusion
Mean RHR above 75–80 b.p.m. was associated with increased risk for cardiovascular outcomes except for stroke. Since in diabetes, high RHR is associated with higher absolute event numbers and patients have higher RHRs, this association might be of particular clinical importance in diabetes. These data suggest that RHR lowering in patients with RHRs above 75–80 b.p.m. needs to be studied in prospective trials to determine if it will reduce outcomes in diabetic and non-diabetic patients at high cardiovascular risk.
Clinical Trial registration
http://clinicaltrials.gov.Unique identifier: NCT00153101.
Abstract Background Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular ...disease (CVD) risk, but these associations have not been examined in ethnically diverse populations. In a multiethnic population-based study of adults in Canada, we assessed the stability of TMAO and L-carnitine in stored serum samples and their association with intimal medial thickness, prevalent risk factors, and clinical events. Methods In a randomly sampled cross-sectional study of 1286 Canadians, fasting serum samples were collected and stored. In 292 consecutive individuals (99 CVD cases and 193 unmatched control subjects), L-carnitine and TMAO concentrations were assessed using validated analytical approaches. Results The mean (± SD) TMAO level was 1.998 ± 3.13 μM and L-carnitine was 42.29 ± 11.35 μM. The relative levels of the samples did not appreciably change after 3 freeze-thaw cycles (coefficient of variation, 5.6% and 4.7%, respectively). No significant association between L-carnitine levels and prevalent CVD was found, with adjustment for covariates (odds ratio, 1.57; 95% confidence interval, 0.58-4.26; P trend = 0.65), for highest vs lowest quintile group. TMAO levels showed a significant, graded association with prevalent CVD (odds ratio, 3.17; 95% confidence interval, 1.05-9.51; P trend = 0.02). After further adjustment for diabetes status, meat, fish, and cholesterol intake, the association remained significant. No significant association between carotid intimal medial thickness and L-carnitine ( P = 0.64) or TMAO ( P = 0.18) was found. Conclusions Serum TMAO and L-carnitine analysis on stored samples is reliable. Our findings support an association between TMAO with prevalent CVD in a multiethnic population. This finding requires replication in larger studies in which dietary intake and stored serum samples exist.
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