Kunal N. Karmali

Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data

BACKGROUND We aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering therapy. METHODS This meta-analysis included individual participant data from trials that randomly assigned patients to either blood pressure-lowering drugs or placebo, or to more intensive or less intensive blood pressure-lowering regimens. The primary outcome was total major cardiovascular events, consisting of stroke, heart attack, heart failure, or cardiovascular death. Participants were separated into four categories of baseline 5-year major cardiovascular risk using a risk prediction equation developed from the placebo groups of the included trials (<11%, 11-15%, 15-21%, >21%). FINDINGS 11 trials and 26 randomised groups met the inclusion criteria, and included 67,475 individuals, of whom 51,917 had available data for the calculation of the risk equations. 4167 (8%) had a cardiovascular event during a median of 4·0 years (IQR 3·4-4·4) of follow-up. The mean estimated baseline levels of 5-year cardiovascular risk for each of the four risk groups were 6·0% (SD 2·0), 12·1% (1·5), 17·7% (1·7), and 26·8% (5·4). In each consecutive higher risk group, blood pressure-lowering treatment reduced the risk of cardiovascular events relatively by 18% (95% CI 7-27), 15% (4-25), 13% (2-22), and 15% (5-24), respectively (p=0·30 for trend). However, in absolute terms, treating 1000 patients in each group with blood pressure-lowering treatment for 5 years would prevent 14 (95% CI 8-21), 20 (8-31), 24 (8-40), and 38 (16-61) cardiovascular events, respectively (p=0·04 for trend). INTERPRETATION Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases. These results support the use of predicted baseline cardiovascular disease risk equations to inform blood pressure-lowering treatment decisions. FUNDING None.BackgroundWe aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform ...

A Systematic Examination of the 2013 ACC/AHA Pooled Cohort Risk Assessment Tool for Atherosclerotic Cardiovascular Disease

BACKGROUND The 2013 American College of Cardiology/American Heart Association updated cholesterol guidelines recommend the use of Pooled Cohort Equations to estimate 10-year absolute risk for atherosclerotic cardiovascular disease (ASCVD) in primary prevention. OBJECTIVES This study sought to systematically examine the Pooled Cohort Equations to determine risk factor levels required to exceed risk thresholds outlined in new cholesterol guidelines. METHODS We entered continuous risk factor levels in isolation and in specified combinations with the risk tool, and we observed predicted risk output patterns. We used the 10-year ASCVD risk threshold of ≥7.5% as a clinically relevant risk threshold. RESULTS We demonstrated that a hypothetical man or woman can reach clinically relevant risk thresholds throughout the eligible age spectrum of 40 to 79 years of age, depending on the associated risk factor burden in all race-sex groups. Age continues to be a major determinant of 10-year ASCVD risk for both men and women. Compared with the previous risk assessment tool used in cholesterol guidelines, the inclusion of a stroke endpoint and use of race-specific coefficients permit identification of at-risk African Americans and non-Hispanic white women at much younger ages and lower risk factor levels. CONCLUSIONS These data provide context of specific risk factor levels and groups of individuals who are likely to have 10-year ASCVD risk estimates ≥7.5%. Age continues to be a major driver of risk, which highlights the importance of the clinician-patient discussion before statin therapy is initiated.

Drugs for Primary Prevention of Atherosclerotic Cardiovascular Disease: An Overview of Systematic Reviews

IMPORTANCE The Million Hearts initiative emphasizes ABCS (aspirin for high-risk patients, blood pressure [BP] control, cholesterol level management, and smoking cessation). Evidence of the effects of drugs used to achieve ABCS has not been synthesized comprehensively in the prevention of primary atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE To compare the efficacy and safety of aspirin, BP-lowering therapy, statins, and tobacco cessation drugs for fatal and nonfatal ASCVD outcomes in primary ASCVD prevention. EVIDENCE REVIEW Structured search of the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), MEDLINE, EMBASE, and PROSPERO International Prospective Systematic Review Trial Register to identify systematic reviews published from January 1, 2005, to June 17, 2015, that reported the effect of aspirin, BP-lowering therapy, statin, or tobacco cessation drugs on ASCVD events in individuals without prevalent ASCVD. Additional studies were identified by searching the reference lists of included systematic reviews, meta-analyses, and health technology assessment reports. Reviews were selected according to predefined criteria and appraised for methodologic quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool (range, 0-11). Studies were independently reviewed for key participant and intervention characteristics. Outcomes that were meta-analyzed in each included review were extracted. Qualitative synthesis was performed, and data were analyzed from July 2 to August 13, 2015. FINDINGS From a total of 1967 reports, 35 systematic reviews of randomized clinical trials were identified, including 15 reviews of aspirin, 4 reviews of BP-lowering therapy, 12 reviews of statins, and 4 reviews of tobacco cessation drugs. Methodologic quality varied, but 30 reviews had AMSTAR ratings of 5 or higher. Compared with placebo, aspirin (relative risk [RR], 0.90; 95% CI, 0.85-0.96) and statins (RR, 0.75; 95% CI, 0.70-0.81) reduced the risk for ASCVD. Compared with placebo, BP-lowering therapy reduced the risk for coronary heart disease (RR, 0.84; 95% CI, 0.79-0.90) and stroke (RR, 0.64; 95% CI, 0.56-0.73). Tobacco cessation drugs increased the odds of continued abstinence at 6 months (odds ratio range, 1.82 [95% CI, 1.60-2.06] to 2.88 [95% CI, 2.40-3.47]), but the direct effects on ASCVD were poorly reported. Aspirin increased the risk for major bleeding (RR, 1.54; 95% CI, 1.30-1.82), and statins did not increase overall risk for adverse effects (RR, 1.00; 95% CI, 0.97-1.03). Adverse effects of BP-lowering therapy and tobacco cessation drugs were poorly reported. CONCLUSIONS AND RELEVANCE This overview demonstrates high-quality evidence to support aspirin, BP-lowering therapy, and statins for primary ASCVD prevention and tobacco cessation drugs for smoking cessation. Treatment effects of each drug can be used to enrich discussions between health care professionals and patients in primary ASCVD prevention.

Identifying Individuals at Risk for Cardiovascular Events Across the Spectrum of Blood Pressure Levels

Background We determined the proportion of atherosclerotic cardiovascular disease (ASCVD) events that occur across the spectrum of systolic blood pressure (SBP) and assessed whether multivariable risk assessment can identify persons who experience ASCVD events at all levels of SBP, including those with goal levels. Methods and Results Participants aged 45 to 64 years from the Framingham Offspring and Atherosclerosis Risk in Communities studies were stratified based on treated and untreated SBP levels (<120, 120 to 129, 130 to 139, 140 to 149, 150 to 159, ≥160 mm Hg). We determined the number of excess ASCVD events in each SBP stratum by calculating the difference between observed and expected events (ASCVD event rate in untreated SBP <120 mm Hg was used as the reference). We categorized participants into 10-year ASCVD risk groups using the Pooled Cohort risk equations. There were 18 898 participants (78% white; 22% black) who were followed for 10 years. We estimated 427 excess ASCVD events, of which 56% (109 of 197) and 50% (115 of 230), respectively, occurred among untreated and treated participants with elevated SBP who were not recommended for antihypertensive therapy. Among untreated participants, 10-year ASCVD risk ≥7.5% identified 64% of those who experienced an ASCVD at 10 years and 30% of those who did not. Multivariable risk assessment was less useful in baseline-treated participants. Conclusions Half of excess ASCVD events occurred in persons with elevated SBP who were not currently recommended for antihypertensive therapy. Multivariable risk assessment may help identify those likely to benefit from further risk-reducing therapies. These findings support consideration of multivariable risk in guiding prevention across the spectrum of SBP.

Estimating Longitudinal Risks and Benefits From Cardiovascular Preventive Therapies Among Medicare Patients: The Million Hearts Longitudinal ASCVD Risk Assessment Tool: A Special Report From the American Heart Association and American College of Cardiology

The Million Hearts Initiative has a goal of preventing 1 million heart attacks and strokes—the leading causes of mortality—through several public health and healthcare strategies by 2017. The American Heart Association and American College of Cardiology support the program. The Cardiovascular Risk Reduction Model was developed by Million Hearts and the Center for Medicare & Medicaid Services as a strategy to assess a value-based payment approach toward reduction in 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD) by implementing cardiovascular preventive strategies to manage the “ABCS” (aspirin therapy in appropriate patients, blood pressure control, cholesterol management, and smoking cessation). The purpose of this special report is to describe the development and intended use of the Million Hearts Longitudinal ASCVD Risk Assessment Tool. The Million Hearts Tool reinforces and builds on the “2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk” by allowing clinicians to estimate baseline and updated 10-year ASCVD risk estimates for primary prevention patients adhering to the appropriate ABCS over time, alone or in combination. The tool provides updated risk estimates based on evidence from high-quality systematic reviews and meta-analyses of the ABCS therapies. This novel approach to personalized estimation of benefits from risk-reducing therapies in primary prevention may help target therapies to those in whom they will provide the greatest benefit, and serves as the basis for a Center for Medicare & Medicaid Services program designed to evaluate the Million Hearts Cardiovascular Risk Reduction Model.

Data Resource Profile: The Cardiovascular Disease Lifetime Risk Pooling Project

Data Resource Profile: The Cardiovascular Disease Lifetime Risk Pooling Project John T Wilkins,* Kunal N Karmali, Mark D Huffman, Norrina B Allen, Hongyan Ning, Jarett D Berry, Daniel B Garside, Alan Dyer and Donald M Lloyd-Jones Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA and Institute for Minority Health Research, The University of Illinois at Chicago College of Medicine, Chicago, IL, USA

Global Risk Assessment to Guide Blood Pressure Management in Cardiovascular Disease Prevention

Elevated blood pressure (BP) is a causal risk factor for cardiovascular disease (CVD). Epidemiological analyses have established the graded and continuous association between higher BP and CVD. Moreover, randomized clinical trials among individuals with hypertension have demonstrated, in aggregate, a reduction in CVD events by 20%, coronary heart disease (CHD) by 17%, stroke by 27%, and heart failure by 28% for every 10 mm Hg systolic BP (SBP) lowering with medical therapy.1 Therefore, prevention, detection, treatment, and control of elevated BP, and its clinical correlate hypertension, is an important public health priority and a primary target for CVD prevention. Although national health surveys have demonstrated improvements in hypertension awareness and treatment, strategic opportunities to improve the efficiency and efficacy of applying BP-lowering therapy in patients most likely to benefit remain.2 Global CVD risk assessment, using multivariable prediction models that estimate absolute CVD risk from routinely measured clinical variables, has been promulgated in several CVD prevention guidelines for cholesterol management to target the most intensive preventive therapies to those at highest absolute CVD risk.3–5 Hypertension guidelines, however, have instead relied solely on isolated BP thresholds and BP goals to guide treatment initiation and intensity. In this review, we provide a rationale for incorporating global CVD risk assessment in BP treatment decision-making and propose a framework to guide its implementation in future CVD prevention guidelines. Epidemiological analyses have firmly established that CVD is a multifactorial condition and that modest increases of several CVD risk factors can often lead to greater overall risk than a severe elevation of a …

Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure: A meta-analysis of individual participant data.

Background Clinical practice guidelines have traditionally recommended blood pressure treatment based primarily on blood pressure thresholds. In contrast, using predicted cardiovascular risk has been advocated as a more effective strategy to guide treatment decisions for cardiovascular disease (CVD) prevention. We aimed to compare outcomes from a blood pressure-lowering treatment strategy based on predicted cardiovascular risk with one based on systolic blood pressure (SBP) level. Methods and findings We used individual participant data from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) from 1995 to 2013. Trials randomly assigned participants to either blood pressure-lowering drugs versus placebo or more intensive versus less intensive blood pressure-lowering regimens. We estimated 5-y risk of CVD events using a multivariable Weibull model previously developed in this dataset. We compared the two strategies at specific SBP thresholds and across the spectrum of risk and blood pressure levels studied in BPLTTC trials. The primary outcome was number of CVD events avoided per persons treated. We included data from 11 trials (47,872 participants). During a median of 4.0 y of follow-up, 3,566 participants (7.5%) experienced a major cardiovascular event. Areas under the curve comparing the two treatment strategies throughout the range of possible thresholds for CVD risk and SBP demonstrated that, on average, a greater number of CVD events would be avoided for a given number of persons treated with the CVD risk strategy compared with the SBP strategy (area under the curve 0.71 [95% confidence interval (CI) 0.70–0.72] for the CVD risk strategy versus 0.54 [95% CI 0.53–0.55] for the SBP strategy). Compared with treating everyone with SBP ≥ 150 mmHg, a CVD risk strategy would require treatment of 29% (95% CI 26%–31%) fewer persons to prevent the same number of events or would prevent 16% (95% CI 14%–18%) more events for the same number of persons treated. Compared with treating everyone with SBP ≥ 140 mmHg, a CVD risk strategy would require treatment of 3.8% (95% CI 12.5% fewer to 7.2% more) fewer persons to prevent the same number of events or would prevent 3.1% (95% CI 1.5%–5.0%) more events for the same number of persons treated, although the former estimate was not statistically significant. In subgroup analyses, the CVD risk strategy did not appear to be more beneficial than the SBP strategy in patients with diabetes mellitus or established CVD. Conclusions A blood pressure-lowering treatment strategy based on predicted cardiovascular risk is more effective than one based on blood pressure levels alone across a range of thresholds. These results support using cardiovascular risk assessment to guide blood pressure treatment decision-making in moderate- to high-risk individuals, particularly for primary prevention.

Achieving and Maintaining Cardiovascular Health Across the Lifespan

The American Heart Association introduced the concept of cardiovascular health (CVH) in its 2020 Strategic lmpact Goals. Defined by the presence of four health behaviors (smoking, weight, diet, and physical activity) and three health factors (glucose, blood pressure, and cholesterol), CVH reflects an expansion of preventive efforts to the entire population and a reframing of disease prevention to health promotion. Recent evidence has confirmed the relevance of the seven CVH metrics in cardiovascular outcomes, highlighting the critical role of a healthy lifestyle in achieving and maintaining CVH through the lifespan. Primordial prevention efforts geared towards health promotion and healthy behaviors, sustained over the life course, and fostered by public health and health policy will be the key to achieving and maintaining CVH and improving the cardiovascular health of the nation.

Predictors of cholesterol treatment discussions and statin prescribing for primary cardiovascular disease prevention in community health centers.

BACKGROUND Although cholesterol guidelines emphasize cardiovascular disease (CVD) risk to guide primary prevention, predictors of statin use in practice are unknown. We aimed to identify factors associated with a cholesterol treatment discussion and statin prescribing in a high-risk population. METHODS We used data from a trial conducted among participants in community health centers without CVD or diabetes and a 10-year coronary heart disease (CHD) risk≥10%. Cholesterol treatment discussion was assessed at 6months and statin prescription at 1year. We used logistic regressions to identify factors associated with each outcome. RESULTS We analyzed 646 participants (89% male, mean age 60±9.5years). Cholesterol treatment discussion occurred in 19% and statin prescription in 12% of participants. Ten-year CHD risk was not associated with treatment discussion (OR 1.11 per 1 SD increase, 95% CI 0.91-1.33) but was associated with statin prescription (OR 1.41 per 1 SD increase, 95% CI 1.13-1.75) in unadjusted models. After adjusting for traditional CVD risk factors that contribute to CHD risk, low-density lipoprotein cholesterol (LDL-C) was independently associated with statin prescription (OR 1.82 per 1 SD increase, 95% CI 1.66-1.99). Antihypertensive medication use was independently associated with both cholesterol treatment discussion (OR 3.68, 95% CI 2.35-5.75) and statin prescription (OR 3.98, 95% CI 3.30-4.81). Other drivers of CVD risk (age, smoking, and systolic blood pressure) were not associated with statin use. CONCLUSIONS Single risk factor management strongly influences cholesterol treatment discussions and statin prescribing patterns. Interventions that promote risk-based statin utilization are needed. TRIAL REGISTRATION Clinicaltrials.gov.: NCT01610609.