domingo, 14 de septiembre de 2014

Study of 1.25 Million Patients Evaluates Risk for 12 CVDs

News Author: Sue Hughes
CME Author: Laurie Barclay, MD
CME/CE Released: 07/29/2014 ; Valid for credit through 07/29/2015

Clinical Context

In 2010, high blood pressure was the leading risk factor for the overall burden of disease worldwide. High-income countries have recently experienced reduced cardiovascular mortality, despite increased prevalence of patients living with cardiovascular disease, thanks to the more widespread use of preventive drugs.
Previous studies have not examined the associations of blood pressure with various types of incident cardiovascular disease in a contemporary population. The goal of this study was to determine whether blood pressure was associated with 12 different manifestations of cardiovascular disease and whether associations varied by age and by systolic vs diastolic elevations.

Study Synopsis and Perspective

New data from a UK study including 1.25 million patients in a primary care setting has drummed home the substantial burden of hypertension and identified some new observations on how blood pressure affects 12 different manifestations of cardiovascular disease, including various forms of stroke.
It finds that a 30-year-old patient with hypertension has a large increase in lifetime risk for a cardiovascular event compared with a normotensive individual (63% compared with 46%) and will develop cardiovascular disease an average of 5 years earlier.
The researchers, led by Eleni Rapsomaniki, PhD, from the Farr Institute for Health Informatics Research, London, United Kingdom, reported associations of blood pressure with a substantially wider range of incident cardiovascular diseases than seen before, across a broader age range (including people younger than 40 years) and a wider range of blood pressure values (including less than 115/75 mm Hg).
For nearly all cardiovascular diseases, there was a linear relation between systolic or diastolic blood pressure with outcomes at all ages, further supporting the absence of a J-shape curve, even in the elderly.
Senior author Harry Hemingway, MD, also from the Farr Institute for Health Informatics Research, commented to Medscape Medical News: "We have produced a treasure trove of data. This is the largest database ever produced on how blood pressure is related to cardiovascular disease. Because we had data on so many patients we could separate out many different clinical pathologies and see how systolic and diastolic blood pressure was related to them. We were also able to look across a wider range of blood pressures than has been done before. This is like improving the magnification in the lens of a microscope to establish greater detail."
He added: "This is contemporary data (up to 2010) from clinicians recording information on real everyday patients in clinical practice. It faithfully replicates what we already know, which proves validation, and it also identifies new associations not examined before."
The study appears in the May 31 issue of The Lancet.
In an accompanying comment, Professor Thomas Kahan, MD, from the Karolinska Institute, Stockholm, Sweden, says the study provides important new information to improve risk assessment, patient counseling, and decision making for patients with hypertension, and he concludes that, "The clinical benefit of improved risk assessment and appropriate treatment might be substantial."
Focus Guidelines to Specific Risks
For the study, researchers analyzed data on blood pressure from electronic medical records and linked those results to other databases on hospital admissions and deaths resulting from 12 different presentations of cardiovascular disease.
Noting that substantial debate has surrounded the benefits of treating mild hypertension in young people, the researchers state, "In the absence of long-term randomized trials, our estimates of lifetime risk and cardiovascular disease-free years of life lost provide epidemiological evidence of substantial morbidity associated with raised blood pressure, irrespective of the starting baseline risk."
They point out that their data on how blood pressure relates to the 12 cardiovascular conditions at various ages can be used to extend the existing counseling of patients and decision making, which is currently based on heart attack and stroke risks alone. They say this "will help to focus guidelines and clinicians to the disease areas in which screening and treatments are more likely to have an effect."
For example, they point out that of the 5 years of cardiovascular disease–free life lost associated with hypertension, nearly half were attributable to stable and unstable angina, whereas in patients aged 80 years and older, heart failure accounted for nearly a fifth of the years of life lost.
Although most of the 12 cardiovascular outcomes investigated correlated better with systolic pressure (with the strongest associations being seen for stable angina and intracerebral and subarachnoidal hemorrhage), abdominal aortic aneurysm (AAA) was weakly associated with systolic pressure and much more strongly associated with diastolic pressure. Professor Hemingway suggested that this observation may improve the selection process for AAA screening.
The authors also found that the age-specific relevance of blood pressure depends on which disease outcome is studied. For example, in patients older than 80 years, stroke, myocardial infarction (MI), and peripheral arterial disease (PAD) were strongly associated with raised blood pressure, whereas unheralded coronary death was not.
"Our data shows that PAD is a common initial presentation of cardiovascular disease in the elderly," Professor Hemingway commented. "This condition has not been well represented in clinical trials in recent years, but our data suggests it should be."
Risk More Important Than Numbers
Another paper in the same issue reports that treatment rates for hypertension have almost doubled and control rates have tripled in England between 1994 and 2011, resulting in the saving of tens of thousands of lives each year.
Although the investigators, led by Emanuela Falaschetti, MSc, from Imperial College London in the United Kingdom, and the authors of the accompanying comment suggest this is a cause for optimism, a Lancet editorial points out that control was achieved in only 37% of patients in 2011 and concludes that, "Clearly, a more concerted effort and different approaches are needed urgently."
Professor Hemingway agrees with the Lancet editorial, pointing out that control of blood pressure is not synonymous with normalization of risk. "If we are doing well with hypertension management, then the risk of cardiovascular disease would be the same whether the patient had a history of hypertension or not. But this is definitely not the case," he told Medscape Medical News.
He added: "Clinicians talk about blood pressure control, meaning that the numbers have been brought back into a certain range. But patients don't care what their numbers are. They care about their risk of MI, stroke, PAD, etc. In our study, we show that among people with hypertension — some controlled, some not controlled — there is a strong association with lifetime risks of many different cardiovascular conditions.
"It is not just about the blood pressure numbers. They must be interpreted within the wider context of overall cardiovascular risk. It is clear that more needs to be done. We need better strategies to lower blood pressure and cardiovascular risk and more support to clinicians to help them implement these strategies."
Professor Hemingway believes the electronic health record is a good place to focus these strategies and support.
"We could build in tools in the records to prompt clinicians to ask certain questions and consider overall cardiovascular risk when assessing blood pressure," he noted. "We could also display the risks to the patient and show how the risks are reduced with various interventions. There is an awful lot more we can do with electronic health records."
The study by Rapsomaniki et al was funded by the Medical Research Council, National Institute for Health Research, and Wellcome Trust. The authors have disclosed no relevant financial relationships. The study by Falaschetti et al received no funding. Falaschetti has disclosed no relevant financial relationships; disclosures for the coauthors appear in the article. Professor Kahan reports he has received research grants from Celladon, Medtronic, Pfizer, and Servier.
Lancet. 2014;383:1861, 1866-1868, 1899-1911, 1912-1919. Rapsomaniki Abstract Falaschetti Abstract Commentary Editorial

Study Highlights

  • The cohort for this study consisted of 1.25 million patients who were at least 30 years old and who had no cardiovascular disease at enrollment.
  • The investigators identified this cohort using linked electronic health records from 1997 to 2010 in the CALIBER (Cardiovascular Research Using Linked Bespoke Studies and Electronic Health Records) program.
  • Of patients in the cohort, 20% were treated with blood pressure–lowering medications.
  • The investigators examined the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases.
  • They also estimated the lifetime risks (up to age 95 years) and cardiovascular disease–free life-years lost, after adjustment for other risk factors at index ages 30, 60, and 80 years.
  • There were 83,098 initial cardiovascular disease presentations during follow-up (median duration, 5.2 years).
  • People with systolic blood pressure of 90 to 114 mm Hg and diastolic blood pressure of 60 to 74 mm Hg had the lowest risk for cardiovascular disease in each age group.
  • There was no evidence of a J-shaped increased risk for cardiovascular disease at lower blood pressures.
  • For various cardiovascular disease endpoints, the effect of high blood pressure varied from strongly positive to no effect.
  • The strongest associations with high systolic blood pressure were for intracerebral hemorrhage (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.32 - 1.58), subarachnoid hemorrhage (HR, 1.43; 95% CI, 1.25 - 1.63), and stable angina (HR, 1.41; 95% CI, 1.36 - 1.46).
  • The weakest association with high systolic blood pressure was for AAA (HR, 1.08; 95% CI, 1.00 - 1.17).
  • Elevated systolic blood pressure had a greater effect on angina, MI, and PAD than did diastolic blood pressure.
  • However, elevated diastolic blood pressure had a greater effect on AAA than did elevated systolic pressure.
  • Pulse pressure was inversely associated with AAA (HR per 10 mm Hg, 0.91; 95% CI, 0.86 - 0.98).
  • Pulse pressure was directly and most strongly associated with PAD (HR, 1.23; 95% CI, 1.20 - 1.27).
  • Lifetime risk of overall cardiovascular disease at age 30 years was 63.3% (95% CI, 62.9% - 63.8%) in people with hypertension (blood pressure ≥140/90 mm Hg or treatment with blood pressure–lowering drugs) compared with 46.1% (95% CI, 45.5% - 46.8%) for those with normal blood pressure.
  • People with hypertension developed cardiovascular disease 5.0 years earlier (95% CI, 4.8 - 5.2 years) than those with normal blood pressure.
  • For persons having hypertension from index age 30 years, stable and unstable angina accounted for 43% of the cardiovascular disease–free years of life lost.
  • For persons having hypertension from index age 80 years, heart failure and stable angina each accounted for 19% of years of life lost.
  • The investigators concluded that their findings do not support conventional wisdom that blood pressure has strong associations with all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant.
  • They also note the substantial lifetime burden of hypertension despite modern treatments, as well as the need for new blood pressure–lowering strategies.

Clinical Implications

  • Findings of a large cohort study do not support conventional wisdom that diastolic and systolic associations with cardiovascular diseases are concordant.
  • These findings also support varying associations of blood pressure with different cardiovascular diseases at different index ages for hypertension. Despite modern treatments, hypertension carries a substantial lifetime burden, highlighting the need for new blood pressure–lowering strategies.

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