Comparing six cardiovascular risk prediction models in Haiti: implications for identifying high-risk individuals for primary prevention.

BACKGROUND: Cardiovascular diseases (CVD) are rapidly increasing in low-middle income countries (LMICs). Accurate risk assessment is essential to reduce premature CVD by targeting primary prevention and risk factor treatment among high-risk groups. Available CVD risk prediction models are built on predominantly Caucasian risk profiles from high-income country populations, and have not been evaluated in LMIC populations. We aimed to compare six existing models for predicted 10-year risk of CVD and identify high-risk groups for targeted prevention and treatment in Haiti. METHODS: We used cross-sectional data within the Haiti CVD Cohort Study, including 1345 adults ≥ 40 years without known history of CVD and with complete data. Six CVD risk prediction models were compared: pooled cohort equations (PCE), adjusted PCE with updated cohorts, Framingham CVD Lipids, Framingham CVD Body Mass Index (BMI), WHO Lipids, and WHO BMI. Risk factors were measured during clinical exams. Primary outcome was continuous and categorical predicted 10-year CVD risk. Secondary outcome was statin eligibility. RESULTS: Sixty percent were female, 66.8% lived on a daily income of ≤ 1 USD, 52.9% had hypertension, 14.9% had hypercholesterolemia, 7.8% had diabetes mellitus, 4.0% were current smokers, and 2.5% had HIV. Predicted 10-year CVD risk ranged from 3.6% in adjusted PCE (IQR 1.7-8.2) to 9.6% in Framingham-BMI (IQR 4.9-18.0), and Spearman rank correlation coefficients ranged from 0.86 to 0.98. The percent of the cohort categorized as high risk using model specific thresholds ranged from 1.8% using the WHO-BMI model to 41.4% in the PCE model (χ2 = 1416, p value < 0.001). Statin eligibility also varied widely. CONCLUSIONS: In the Haiti CVD Cohort, there was substantial variation in the proportion identified as high-risk and statin eligible using existing models, leading to very different treatment recommendations and public health implications depending on which prediction model is chosen. There is a need to design and validate CVD risk prediction tools for low-middle income countries that include locally relevant risk factors. TRIAL REGISTRATION: clinicaltrials.gov NCT03892265 .

Intensive blood-pressure control in hypertensive chronic kidney disease.

BACKGROUND: In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS: We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS: During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27). However, the effects differed according to the baseline level of proteinuria (P=0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01). CONCLUSIONS: In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)

Renal outcomes in hypertensive Black patients at high cardiovascular risk.

The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydrochlorothiazide or amlodipine and titrated in parallel to reach recommended blood pressure goals. Of the 8125 participants in the United States, 1414 were of self-described Black ethnicity. The composite kidney disease end point, defined as a doubling in serum creatinine, end-stage renal disease, or death was not different between Black and non-Black patients, although the Blacks were significantly more likely to develop a greater than 50% increase in serum creatinine to a level above 2.6 mg/dl. We found important early differences in the estimated glomerular filtration rate (eGFR) due to acute hemodynamic effects, indicating that benazepril plus amlodipine was more effective in stabilizing eGFR compared to benazepril plus hydrochlorothiazide in non-Blacks. There was no difference in the mean eGFR loss in Blacks between therapies. Thus, benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression. Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.

Predictors of systolic BP <140 mmHg and systolic BP level by randomly assigned treatment group (benazepril plus amlodipine or hydrochlorothiazide) in the ACCOMPLISH Study.

BACKGROUND: The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a systolic blood pressure (SBP) <140 mmHg and achieved SBP level by the end of 12 months in both treatment groups. METHODS: Baseline and 12-month SBP was available in 10,506 patients, of whom 6250 had diabetes. Univariate and multivariate logistic regression models were used for SBP control at 12 months and multivariable regression models were used for the prediction of SBP at 12 months. A stepwise procedure was used to select significant (p < 0.001) predictors in multivariate analyses. RESULTS: Mean (± SD) BP fell from 145.4/80.1 (± 18.3/10.7) mmHg at randomization to 132.8/74.7 (± 16.0/9.6) mmHg at 12 months. The main baseline predictors of SBP control <140 mmHg were region (USA >Nordic region) and Caucasian ethnicity in both randomization arms. A higher diastolic BP and the use of lipid lowering agents indicated favorable effects in the B+H arm only. The predictors of uncontrolled SBP were: (i) higher baseline SBP values, (ii) higher number of previous antihypertensive medications in both arms, (iii) the previous use of insulin in the B+A arm, and (iv) pre-trial calcium channel blocker (CCB) use in the B+H arm. Additionally, pre-trial use of thiazides and electrocardiogram (ECG)-left ventricular hypertrophy (LVH) at baseline predicted higher, and smoking lower absolute SBP in the B+A arm and the use of thiazides and proteinuria a higher SBP in the B+H arm. CONCLUSION: Irrespective of treatment, patients in the USA and Caucasians achieved better SBP control, whereas higher baseline SBP and more previous antihypertensive medications indicated less control. Concomitant use of lipid lowering treatment indicated a better SBP control in the benazepril + hydrochlorothiazide arm. Lastly, insulin use and ECG-LVH in the benazepril + amlodipine arm and proteinuria in the benazepril + hydrochlorothiazide arm indicated poor control.

Self-Reported Antihypertensive Medication Class and Temporal Relationship to Treatment Guidelines.

The greater antihypertensive responses to initial therapy with calcium channel blockers (CCBs) or thiazide-type diuretics than renin-angiotensin system blockers as initial therapy in non-Hispanic Black (NHB) adults was recognized in the US High BP guidelines from 1988 to 2003. The 2014 Report from Panel Members Appointed to the Eighth Joint National Committee (2014 aJNC8 Report) and the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline were the first to recommend CCBs or thiazide-type diuretics rather than renin-angiotensin system blockers as initial therapy in NHB. We assessed the temporal relationship of these recommendations on self-reported CCB or thiazide-type diuretics monotherapy by NHB and NHW adults with hypertension absent compelling indications for ß-blockers or renin-angiotensin system blockers in National Health and Nutrition Examination Surveys 2015 to 2018 versus 2007 to 2012 (after versus before 2014 aJNC8 Report). CCB or thiazide-type diuretics monotherapy was unchanged in NHW adults (17.1% versus 18.1%, P=0.711) and insignificantly higher after 2014 among NHB adults (43.7% versus 38.2%, P=0.204), although CCB monotherapy increased (29.5% versus 21.0%, P=0.021) and renin-angiotensin system blocker monotherapy fell (44.5% versus 31.0%, P=0.008). Although evidence-based CCB monotherapy increased among NHB adults in 2015 to 2018, hypertension control declined as untreated hypertension and monotherapy increased. While a gap between recommended and actual monotherapy persists, evidence-based monotherapy appears insufficient to improve hypertension control in NHB adults, especially given evidence for worsening therapeutic inertia. Initiating treatment with single-pill combinations and timely therapeutic intensification when required to control hypertension are evidence-based, race-neutral options for improving hypertension control among NHB adults.

Cardiovascular Benefits of Angiotensin-Converting Enzyme Inhibition Plus Calcium Channel Blockade in Patients Achieving Tight Blood Pressure Control and With Resistant Hypertension.

BACKGROUND: The 2017 hypertension guidelines lowered systolic blood pressure (BP) goals to <130 mm Hg and redefined resistant hypertension. We investigated if these changes alter the cardiovascular benefits demonstrated by combining a calcium channel blocker (CCB), rather than hydrochlorothiazide (HCTZ), with an angiotensin-converting enzyme inhibitor (ACEI). METHODS: In this post hoc analysis of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension trial (n = 11,506), we compared the primary composite outcome (cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization) between the 2 combination-treatment limbs in patients achieving a systolic BP ≤130 mm Hg and those with "apparent resistant hypertension" (prescribed ≥4 antihypertensive medications). RESULTS: Among study patients, 5,221 (45.4%) achieved a systolic BP ≤130 mm Hg. There were fewer primary endpoints in the amlodipine/benazepril (9.2%) vs. the HCTZ/benazepril (10.9%) limb (adjusted hazard ratio [HR] 0.83, 95% confidence interval [CI], 0.70-0.99). There were also fewer primary endpoints in the amlodipine/benazepril (12.8%) vs. the HCTZ/benazepril (15.2%) limb (n = 4,451, 38.7%) among patients with apparent resistant hypertension (HR 0.81, 95% CI, 0.70-0.95). CONCLUSIONS: Combination therapy adding a CCB, rather than HCTZ, to an ACEI was more effective in preventing composite cardiovascular events even in hypertensive patients achieving aggressive systolic BP targets as well as in those with apparent resistant hypertension. Our findings add support that most patients, including those following contemporary clinical guidelines, will benefit from this combination. CLINICAL TRIALS REGISTRATION: Trial Number NCT00170950.

Blood content of asymmetric dimethylarginine: new insights into its dysregulation in renal disease.

BACKGROUND: Plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is significantly elevated in patients with kidney disease and is a potential risk factor for cardiovascular disease. Here, we tested whether human whole blood (WB), as in rodent blood, can accumulate free ADMA and whether this accumulation is a function of disease burden. METHODS: In 16 healthy control subjects (CO), 18 patients with ESRD and 18 matched hypertensive patients with normal renal function (HTN), we compared using high-pressure liquid chromatography baseline plasma and WB supernatant (WBSUP) ADMA and symmetrical dimethylarginine (SDMA) concentrations and accumulation during a 5-h incubation. We measured protein turnover in incubated WBSUP to determine if proteolytic processes drive ADMA accumulation. RESULTS: Elevated plasma ADMA was confirmed in ESRD and HTN populations while basal WBSUP ADMA was significantly higher in ESRD subjects than controls (P = 0.05 versus CO; P = 0.02 versus HTN). Plasma SDMA followed a similar pattern. Incubation of WBSUP resulted in ADMA release from protein-incorporated stores while SDMA was unaffected. ADMA accumulation in ESRD samples was significantly greater than that in HTN (P = 0.03). CO and HTN men showed significantly greater ADMA accumulation than women (P = 0.01 and P = 0.003, respectively) but no gender difference was observed in the ESRD group (P = 0.26). ADMA accumulation correlated with ex vivo protein turnover (R = 0.76, P < 0.0001). CONCLUSIONS: Human blood is capable of releasing physiologically significant quantities of ADMA via proteolytic pathways. Dysregulated ADMA release from WB reservoirs may contribute to the distinctly high plasma ADMA levels in ESRD populations.

Periodontal disease and other nontraditional risk factors for CKD.

BACKGROUND: Chronic kidney disease, undiagnosed in a significant number of adults, is a public health problem. Given the systemic inflammatory response to periodontal disease, we hypothesized that periodontal disease could be associated with chronic kidney disease. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: We identified 12,947 adults 18 years or older with information for kidney function and at least one risk factor in the Third National Health and Nutrition Examination Survey. PREDICTOR: The main predictor was periodontal status. Other nontraditional and traditional risk factors included socioeconomic status, health status, health behavior, biomarker levels, anthropometric assessment, and health care utilization. OUTCOMES & MEASUREMENTS: Chronic kidney disease was defined using the Kidney Disease Outcomes Quality Initiative stages 3 and 4 with a moderate to severe decrease in kidney function (glomerular filtration rate, 15 to 59 mL/min/1.73 m(2)). Univariable and multivariable logistic regression models assessed the associations between chronic kidney disease and periodontal disease and other nontraditional risk factors. RESULTS: Chronic kidney disease prevalence was 3.6%; periodontal disease prevalence was 6.0%; and edentulism prevalence was 10.5%. Adults with periodontal disease and edentulous adults were twice as likely to have chronic kidney disease (adjusted odds ratio, 1.60; 95% confidence interval, 1.16 to 2.21; adjusted odds ratio, 1.85; 95% confidence interval, 1.34 to 2.56, respectively) after simultaneously adjusting for other traditional and nontraditional risk factors. LIMITATIONS: Temporal association is unknown. CONCLUSIONS: Periodontal disease and its severe consequence, edentulism, were independently associated with chronic kidney disease after adjusting for other traditional and nontraditional risk factors. This model could contribute to identifying individuals at risk of chronic kidney disease and reduce its burden.

Combining RAAS and calcium channel blockade: ACCOMPLISH in perspective.

The Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial was the first trial to compare the cardiovascular outcomes of initial fixed-dose combination angiotensin-converting enzyme inhibitor (ACEI)/calcium channel blocker (CCB) and ACEI/diuretic therapy in patients with hypertension and high risk of cardiovascular events. The initial combination therapy was effective in this population, with ACEI/CCB therapy providing the greatest benefit (reduction in risk of cardiovascular events). Whether or not the findings of ACCOMPLISH can be applied to other renin-angiotensin-aldosterone system (RAAS) inhibitor/CCB combinations, such as angiotensin receptor blocker (ARB)/CCB combinations, has yet to be investigated. The present report reviews the results of ACCOMPLISH, data from trials comparing ARB and ACEI therapies, and findings from studies of ARB/CCB combination therapy that support the use and further study of combination therapy with RAAS inhibitors and CCBs.

Prompt, aggressive BP lowering in high-risk patients.

Various populations with hypertension have been singled out by current treatment guidelines as requiring more specific treatment. These include patients with stage 2 hypertension, black patients, and patients with coexistent diabetes mellitus and coronary heart disease. Hypertension in these groups is often associated with higher risk of cardiovascular morbidity and mortality. This article reviews current knowledge regarding hypertension in high-risk patient populations, with a particular focus on the importance of prompt, aggressive treatment to lower blood pressure and prevent cardiovascular disease progression. Such treatment includes the early use of multiple-drug therapy with agents that have complementary blood pressure-lowering mechanisms and provide protection from target organ damage. While 2- or 3-drug antihypertensive therapy in these high-risk groups has typically included a diuretic, other combinations of agents may be indicated. Evidence suggests that therapy with a calcium channel blocker and an inhibitor of the renin-angiotensin system is one effective strategy for lowering blood pressure and improving outcomes in these populations.

Prior Medications and the Cardiovascular Benefits From Combination Angiotensin-Converting Enzyme Inhibition Plus Calcium Channel Blockade Among High-Risk Hypertensive Patients.

BACKGROUND: The ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension) trial demonstrated that combination therapy using amlodipine, rather than hydrochlorothiazide, in conjunction with benazepril provided greater cardiovascular risk reduction among high-risk hypertensive patients. Few trials have evaluated the effect of prior antihypertensive therapy used among participants on the study outcomes. METHODS AND RESULTS: In a post hoc observational analysis, we examined the characteristics of the drug regimens taken before trial enrollment in the context of the primary composite outcome (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization). In the "primary subgroup" (n=4475), patients previously taking any renin-angiotensin system blockade plus either a diuretic or a calcium channel blocker alone or as part of their antihypertensive regimen, there were 206 of 2193 (9.4%) versus 281 of 2282 (12.3%) primary composite events among those randomized to combination therapy involving amlodipine versus hydrochlorothiazide, respectively (adjusted Cox proportional hazard ratio, 0.74; 95% confidence interval, 0.62-0.89; P=0.0015). All other participants (n=6975) previously taking any antihypertensive regimen not included in the primary subgroup also benefited from randomization to amlodipine plus benazepril (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72-0.98; P=0.024). Outcomes among most other subgroups, including patients previously taking lipid-lowering medications or dichotomized by prior blood pressure control status, showed similar results. CONCLUSIONS: When combined with an angiotensin-converting enzyme inhibitor, amlodipine provides cardiovascular risk reduction superior to hydrochlorothiazide, largely regardless of prior medication use. These findings add further support for the initial use of this combination regimen among high-risk hypertensive patients.

The management of hypertension in the African American patient.

A panel was convened to discuss the topic of the management of hypertension in the African American patient. Jackson T. Wright, MD, PhD, Professor of Medicine, Case Western Reserve University, Cleveland, OH, moderated the panel. Kenneth A. Jamerson, MD, Professor of Medicine, University of Michigan, Ann Arbor, MI, and Keith C. Ferdinand, MD, Association of Black Cardiologists, Inc, and Emory University, Atlanta, GA, participated in the discussion. This expert panel discussion was supported by Novartis and each author received an honorarium from Novartis for time and effort spent participating in the discussion and reviewing the transcript for important intellectual content prior to publication. The authors maintained full control of the discussion and the resulting content of this article; Novartis had no input in the choice of topic, speakers, or content.

The bases of goal setting in the self-regulation of hypertension.

We apply a new methodology to investigate goal setting by hypertensive patients that uncovers the reasons why people have a goal to manage hypertension or not (e.g. to reduce/maintain one's current blood pressure). The reasons are found to consist of superordinate goals in support of one's focal hypertension goal and the hierarchical mental network underlying the superordinate goals. We show that, not only do such superordinate goals influence patients' beliefs, feelings and decisions, but the relationships among superordinate goals are particularly efficacious in the formation of beliefs and attitudes, as well as intentions to self-regulate hypertension and actual efforts in doing so. Hypotheses were tested on a sample of 219 patients at a university-based hypertension clinic.