Comparing PCSK9 Monoclonal Antibody Treatment Strategies Following Myocardial Infarction Using Negative Control Outcomes: A Target Trial Emulation Study.

BACKGROUND: Initiation of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9 mAb) for lipid-lowering following myocardial infarction (MI) is likely affected by patients' prognostic factors, potentially leading to bias when comparing real-world treatment effects. METHODS: Using target-trial emulation, we assessed potential confounding when comparing two treatment strategies post-MI: initiation of PCSK9 mAb within 1 year and no initiation of PCSK9 mAb. We identified MI hospitalizations during July 2015-June 2020 for patients aged ≥18 years in Optum's de-identified Clinformatics® Data Mart (CDM) and MarketScan, and aged ≥66 in US Medicare claims database. We estimated 3-year counterfactual cumulative risk and risk difference (RD) for 10 negative control outcomes using the clone-censor-weight approach to address time-varying confounding and immortal person-time. RESULTS: PCSK9 mAb initiation within 1-year post-MI was low (0.7% in MarketScan and 0.4% in both CDM and Medicare databases). In CDM, there was a lower risk for cancer (RD = -3.6% [95% CI: -4.3%, -2.9%]), decubitus ulcer (RD = -7.7% [95% CI: -11.8%, -3.7%]), fracture (RD = -8.1% [95% CI: -9.6%, -6.6%]), influenza vaccine (RD = -9.3% [95% CI: -17.5%, -1.1%]), and visual test (RD = -0.6% [95% CI: -0.7%, -0.6%]) under the PCSK9 mAb initiation vs. no initiation strategy. Similar differences persisted in the MarketScan and Medicare databases. In each database, ezetimibe and low-density lipoprotein testing were unbalanced between treatment strategies. CONCLUSION: A comparative effectiveness study of these treatments using the current approach would likely bias results due to the low number of PCSK9 mAb initiators.

Association Between Young Adult Characteristics and Blood Pressure Trajectories.

BACKGROUND: Blood pressure (BP) trajectories from young adulthood through middle age are associated with cardiovascular risk. We examined the associations of hypertension risk factors with BP trajectories among a large diverse sample. METHODS AND RESULTS: We analyzed data from young adults, aged 18 to 39 years, with untreated BP <140/90 mm Hg at baseline from Kaiser Permanente Southern California (N=355 324). We used latent growth curve models to identify 10-year BP trajectories and to assess the associations between characteristics in young adulthood and BP trajectories. We identified the following 5 distinct systolic BP trajectories, which appeared to be determined mainly by the baseline BP with progressively higher BP at each year: group 1 (lowest BP trajectory, 7.9%), group 2 (26.5%), group 3 (33.0%), group 4 (25.4%), and group 5 (highest BP trajectory, 7.3%). Older age (adjusted odds ratio for 30-39 versus 18-29 years, 1.23 [95% CI, 1.18-1.28]), male sex (13.38 [95% CI, 12.80-13.99]), obesity (body mass index ≥30 versus 18.5-24.9 kg/m2, 14.81 [95% CI, 14.03-15.64]), overweight (body mass index 25-29.9 versus 18.5-24.9 kg/m2, 3.16 [95% CI, 3.00-3.33]), current smoking (1.58 [95% CI, 1.48-1.67]), prediabetes (1.21 [95% CI, 1.13-1.29]), diabetes (1.60 [95% CI, 1.41-1.81]) and high low-density lipoprotein cholesterol (≥160 versus <100 mg/dL, 1.52 [95% CI, 1.37-1.68]) were associated with the highest BP trajectory (group 5) compared with the reference group (group 2). CONCLUSIONS: Traditional hypertension risk factors including smoking, diabetes, and elevated lipids were associated with BP trajectories in young adults, with obesity having the strongest association with the highest BP trajectory group.

Trends in the prevalence of multiple chronic conditions among US adults with hypertension from 1999-2000 through 2017-2020.

BACKGROUND: The prevalence of many chronic conditions has increased over the past several decades among US adults. Many adults with hypertension have other chronic conditions. METHODS: We estimated changes in the age-adjusted prevalence of multiple (≥3) chronic conditions, not including hypertension, using data from the National Health and Nutrition Examination Survey, from 1999-2000 to 2017-2020, among US adults with and without hypertension (24,851 and 24,337 participants, respectively). Hypertension was defined as systolic blood pressure (BP) ≥130 mmHg, diastolic BP ≥80 mmHg, or self-reported antihypertensive medication use. We studied 14 chronic conditions: arthritis, asthma, cancer, coronary heart disease, chronic kidney disease, depression, diabetes, dyslipidemia, hepatitis-B, hepatitis-C, heart failure, lung disease, obesity, and stroke. RESULTS: From 1999-2000 to 2017-2020, the age-adjusted mean number of chronic conditions increased more among US adults with versus without hypertension (2.2 to 2.8 versus 1.7 to 2.0; p-interaction<0.001). Also, the age-adjusted prevalence of multiple chronic conditions increased from 39.0% to 52.0% among US adults with hypertension and from 26.0% to 30.0% among US adults without hypertension (p-interaction=0.022). In 2017-2020, after age, gender, and race/ethnicity adjustment, US adults with hypertension were 1.94 (95% CI: 1.72-2.18) times as likely to have multiple chronic conditions compared to those without hypertension. In 2017-2020, dyslipidemia, obesity, and arthritis were the most common 3 co-occurring chronic conditions among US adults with and without hypertension (age-adjusted prevalence 16.5% and 3.1%, respectively). CONCLUSION: In 2017-2020, more than half of US adults with hypertension had ≥3 additional chronic conditions, a substantial increase from 20 years ago.

Atherosclerotic cardiovascular disease events among adults with high predicted risk without established risk factors.

Objective: Age is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk <7.5 %. Methods: We analyzed data from REasons for Geographic and Racial Differences in Stroke study participants, 45-79 years old, without ASCVD or diabetes, not taking statins and with low-density lipoprotein cholesterol 70-189 mg/dL. Participants were categorized into 3 groups based on their 10-year predicted ASCVD risk and presence of established risk factors: <7.5 %, ≥7.5 % with established risk factors and ≥7.5 % without established risk factors. Established risk factors included smoking, systolic blood pressure ≥130 mmHg or antihypertensive medication use, total cholesterol ≥200 mg/dL, or high-density lipoprotein cholesterol <50 mg/dL for women (<40 mg/dL for men). Participants were followed for ASCVD events. Results: Among 11,115 participants, 911 incident ASCVD events occurred over a median of 11.1 years. ASCVD incidence rates were 3.6, 12.8, and 9.8 per 1,000 person-years for participants with predicted risk <7.5 %, predicted risk ≥7.5 % with established risk factors and predicted risk ≥7.5 % without established risk factors, respectively. Compared to adults with predicted risk <7.5 %, hazard ratios for incident ASCVD in participants with risk ≥7.5 % with and without established risk factors were 3.58 (95 %CI 3.03 - 4.21) and 2.72 (95 %CI 1.91-3.88), respectively. Conclusions: Adults with a 10-year predicted ASCVD risk ≥7.5 % but without established risk factors had a high ASCVD incidence.

Multimorbidity is associated with lower total 24-hour movement activity among US adults.

Objective: Having chronic conditions may result in reduced physical and cognitive function but less is known about multimorbidity with daily movement. We examined the association of multimorbidity and device-measured total daily movement in a nationally representative sample of US adults aged ≥ 30 years from the 2011-2014 National Health and Nutrition Examination Surveys. Methods: Any multimorbidity (≥2 conditions) and complex multimorbidity (≥3 conditions across ≥ 3 body systems) were quantified using 16 chronic conditions via self-report and/or clinical thresholds. Total movement over 24-hours (Monitor-Independent Movement Summary units [MIMS-units]) was measured using a wrist-worn device (ActiGraph GT3X). Multivariable linear regression examined the association of 1) each chronic condition, 2) number of conditions, 3) any multimorbidity, and 4) complex multimorbidity with total movement. Covariates included age, gender, race/ethnicity, educational attainment, and smoking status. Results: Among US adults (N = 7304, mean age: 53.2 ± 0.34 years, 53.2% female, 69.4% Non-Hispanic White), 62.2% had any multimorbidity with 34.2% having complex multimorbidity. After adjustment, a higher number of chronic conditions was associated with incrementally lower total movement (ß MIMS-units [95% CI] compared to those with no chronic conditions; one: -419 [-772, -66], two: -605 [-933, -278], three: -1201 [-1506, -895], four: -1908 [-2351, -1465], 5+: -2972 [-3384, -2560]). Complex multimorbidity presence was associated with -1709 (95% CI: -2062, -1357) and -1269 (-1620, -918) lower total movement compared to those without multimorbidity and multimorbidity but not complex, respectively. Conclusions: Multimorbidity was associated with lower 24-h movement among US adults and may be helpful for identifying adults at risk for low movement.

Age-Related Differences in the Role of Risk Factors for Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Reports assessing the association of stroke risk factors with incident stroke have generally assumed a uniform magnitude of associations across the age spectrum, an assumption we assess in this report. METHODS: Participants enrolled 2003-2007 in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study who were stroke free at baseline were followed for incident stroke. Associations of traditional stroke risk factors with incident stroke were assessed using (1) proportional hazards analysis based on the baseline age of the participant and (2) Poisson regression analysis assessing associations based on the changing age of the participant during their follow-up (age at exposure). In each analysis, age strata were selected to have a similar number of strokes in each stratum, specifically 45-64, 65-73, and 74+ years for the proportional hazards analysis and 45-69, 70-79, and 80+ years for Poisson regression. RESULTS: A total of 1,405 ischemic stroke events occurred among 28,235 participants over a median follow-up of 11.3 years, with a total of 276,074 person-years exposure. For both analytic approaches, the magnitude of the association with stroke was significantly less at older ages for diabetes (hazard or relative risk decreasing from ≈2.0 in younger strata to ≈1.3 in older strata), heart disease (from ≈2.0 to ≈1.3), and hypertension defined at a threshold of 140/90 mm Hg (from ≈1.80 to ≈1.50); however, there was no age-related difference in the magnitude of the association for smoking, atrial fibrillation, or left ventricular hypertrophy. DISCUSSION: Hypertension and diabetes are 2 of the more important risk factors for stroke; however, their association with stroke risk appears substantially less at older ages. That the magnitude of the association for smoking, atrial fibrillation, and left ventricular hypertrophy does not decrease with age suggests their relative importance in determining stroke risk likely increases with age.

Associations of body mass index, fasting insulin, and inflammation with mortality: a prospective cohort study.

BACKGROUND/OBJECTIVES: Obesity is often considered to increase the risk for premature mortality. Higher fasting insulin and c-reactive protein are associated with higher body mass index (BMI) and all-cause mortality, so may confound the association between obesity and mortality. Our objective was to determine the independent associations between BMI, fasting insulin, c-reactive protein, and all-cause mortality in a general population sample. METHODS: This prospective cohort study included non-institutionalized US adults (≥20 years) from the National Health and Nutrition Examination Surveys 1999-2000 to 2013-2014. The main exposures of interest were BMI, fasting insulin, c-reactive protein. Mortality data were obtained through linking participants to the National Death Index (ending December 31, 2015). RESULTS: There were 12,563 participants with a median age of 45 years (range 20-85) and 47.9% were male. The median BMI was 27 kg/m2 (IQR 24-32), median fasting insulin was 54 pmol/L (IQR 35-87), and median c-reactive protein was 1.9 mg/L (IQR 0.8-4.4). In a Cox model adjusted for age, biological sex, cigarette smoking, and ten chronic conditions, higher BMI parameterized with quadratic and linear terms was not associated with mortality. When fasting insulin and the natural logarithm of c-reactive protein were included in the model, an inverse association between BMI and mortality was present (compared to the referent category of 5th percentile: 1st percentile, HR 1.10, 95% CI 1.06-1.13; 99th percentile, HR 0.48, 95% CI 0.34-0.69). In contrast, higher levels of fasting insulin and c-reactive protein were associated with an increased risk of mortality (for fasting insulin: 1st percentile, HR 0.98, 95% CI 0.97-0.99; 99th percentile, HR 1.83, 95% CI 1.48-2.26; for c-reactive protein, 1st percentile, HR 0.87, 95% CI 0.84-0.90; 99th percentile, HR 2.77, 95% CI 2.12-3.62). CONCLUSIONS: Higher fasting insulin and higher c-reactive protein confound the association between BMI and the risk of all-cause mortality. The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity.

Prevalence, risk factors, and cardiovascular disease outcomes associated with persistent blood pressure control: The Jackson Heart Study.

BACKGROUND: Maintaining blood pressure (BP) control over time may contribute to lower risk for cardiovascular disease (CVD) among individuals who are taking antihypertensive medication. METHODS: The Jackson Heart Study (JHS) enrolled 5,306 African-American adults ≥21 years of age and was used to determine the proportion of African Americans that maintain persistent BP control, identify factors associated with persistent BP control, and determine the association of persistent BP control with CVD events. This analysis included 1,604 participants who were taking antihypertensive medication at Visit 1 and had BP data at Visits 1 (2000-2004), 2 (2005-2008), and 3 (2009-2013). Persistent BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg at all three visits. CVD events were assessed from Visit 3 through December 31, 2016. Hazard ratios (HR) for the association of persistent BP control with CVD outcomes were adjusted for age, sex, systolic BP, smoking, diabetes, and total and high-density lipoprotein cholesterol at Visit 3. RESULTS: At Visit 1, 1,226 of 1,604 participants (76.4%) with hypertension had controlled BP. Overall, 48.9% of participants taking antihypertensive medication at Visit 1 had persistent BP control. After multivariable adjustment for demographic, socioeconomic, clinical, behavioral, and psychosocial factors, and access-to-care, participants were more likely to have persistent BP control if they were <65 years of age, women, had family income ≥$25,000 at each visit, and visited a health professional in the year prior to each visit. The multivariable adjusted HR (95% confidence interval) comparing participants with versus without persistent BP control was 0.71 (0.46-1.10) for CVD, 0.68 (0.34-1.34) for coronary heart disease, 0.65 (0.27-1.52) for stroke, and 0.55 (0.33-0.90) for heart failure. CONCLUSION: Less than half of JHS participants taking antihypertensive medication had persistent BP control, putting them at increased risk for heart failure.

Medication-Naïve Blood Pressure and Incident Cancers: Analysis of 2 Nationwide Population-Based Databases.

BACKGROUND: Results of preceding studies on the relationship between blood pressure (BP) and cancers have been confounded due to individuals taking antihypertensive medications or shared risk factors. We assessed whether medication-naïve high BP is a risk factor for incident cancers. METHODS: This retrospective observational study included 1,388,331 individuals without a prior history of cancer and not taking antihypertensive medications enrolled in the JMDC Claims Database between 2005 and 2018. The primary outcome was 16 cancers. RESULTS: The median [interquartile range] age was 45 [40-52] years and 56.2% were men. Mean systolic BP (SBP) and diastolic BP (DBP) were 117.7 ± 15.8 and 72.8 ± 11.6 mm Hg. Multivariate Cox regression analysis demonstrated that SBP per 1-SD was associated with a higher incidence of thyroid (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.03-1.16), esophageal (HR: 1.15, 95% CI: 1.07-1.24), colorectal (HR: 1.04, 95% CI: 1.01-1.07), liver (HR: 1.11, 95% CI: 1.03-1.20), and kidney (HR: 1.22, 95% CI: 1.14-1.31) cancers, but with a lower incidence of stomach cancer (HR: 0.94, 95% CI: 0.91-0.98). These associations remained significant after adjustment for multiple testing. DBP was associated with higher incidences of thyroid, esophageal, colorectal, kidney, and corpus uteri cancers, but with a lower incidence of stomach cancer. The associations between SBP and incidences of thyroid, esophageal, colorectal, liver, and kidney cancers were confirmed in the Korean National Health Insurance Service database. CONCLUSIONS: Medication-naïve BP was associated with higher incidences of thyroid, esophageal, colorectal, liver, and kidney cancers. Uncovering the underlying mechanisms for our results may help identify novel therapeutic approach for hypertension and cancer.

High Lead Exposure Associated With Higher Blood Pressure in Haiti: a Warning Sign for Low-Income Countries.

Cardiovascular disease is the leading cause of death in lower-income countries including Haiti. Environmental lead exposure is associated with high blood pressure and cardiovascular mortality in high-income countries but has not been systematically measured and evaluated as a potential modifiable cardiovascular risk factor in lower-income countries where 6.5 billion people reside. We hypothesized lead exposure is high in urban Haiti and associated with higher blood pressure levels. Blood lead levels were measured in 2504 participants ≥18 years enrolled in a longitudinal population-based cohort study in Port-au-Prince. Lead screening was conducted using LeadCare II (detection limit ≥3.3 µg/dL). Levels below detection were imputed by dividing the level of detection by √2. Associations between lead (quartiles) and systolic blood pressure and diastolic blood pressure were assessed, adjusting for age, sex, obesity, smoking, alcohol, physical activity, income, and antihypertensive medication use. The median age of participants was 40 years and 60.1% were female. The geometric mean blood lead level was 4.73µg/dL, 71.1% had a detectable lead level and 42.3% had a blood lead level ≥5 µg/dL. After multivariable adjustment, lead levels in quartile four (≥6.5 µg/dL) compared with quartile 1 (<3.4 µg/dL) were associated with 2.42 mm Hg (95% CI, 0.36-4.49) higher systolic blood pressure and 1.96 mm Hg (95% CI, 0.56-3.37) higher diastolic blood pressure. In conclusion, widespread environmental lead exposure is evident in urban Haiti, with higher lead levels associated with higher systolic and diastolic blood pressure. Lead is a current and potentially modifiable pollutant in lower-income countries that warrants urgent public health remediation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03892265.

Untreated Hypertension and Subsequent Incidence of Colorectal Cancer: Analysis of a Nationwide Epidemiological Database.

Background Studies of the association of hypertension with incident colorectal cancer (CRC) may have been confounded by including individuals taking antihypertensive medication, at high risk for CRC (ie, colorectal polyps and inflammatory bowel disease), or with shared risk factors (eg, obesity and diabetes). We assessed whether adults with untreated hypertension are at higher risk for incident CRC compared with those with normal blood pressure (BP), and whether any association is evident among individuals without obesity or metabolic abnormalities. Methods and Results Analyses were conducted using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018 (n=2 220 112; mean age, 44.1±11.0 years; 58.4% men). Participants who were taking antihypertensive medications or had a history of CRC, colorectal polyps, or inflammatory bowel disease were excluded. Each participant was categorized as having normal BP (systolic BP [SBP]<120 mm Hg and diastolic BP [DBP] <80 mm Hg, n=1 164 807), elevated BP (SBP 120-129 mm Hg and DBP <80 mm Hg, n=341 273), stage 1 hypertension (SBP 130-139 mm Hg or DBP 80-89 mm Hg, n=466 298), or stage 2 hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg, n=247 734). Over a mean follow-up of 1112±854 days, 6899 incident CRC diagnoses occurred. After multivariable adjustment, compared with normal BP, hazard ratios for incident CRC were 0.93 (95% CI, 0.85-1.01) for elevated BP, 1.07 (95% CI, 0.99-1.15) for stage 1 hypertension, and 1.17 (95% CI, 1.08-1.28) for stage 2 hypertension. The hazard ratios for incident CRC for each 10-mm Hg-higher SBP or DBP were 1.04 (95% CI, 1.02-1.06) and 1.06 (95% CI, 1.03-1.09), respectively. These associations were present among adults who did not have obesity, high waist circumference, diabetes, or dyslipidemia. Conclusions Higher SBP and DBP, and stage 2 hypertension are associated with a higher risk for incident CRC, even among those without shared risk factors for CRC. BP measurement could identify individuals at increased risk for subsequent CRC.

A prospective study of multiple sleep dimensions and hypertension risk among white, black and Hispanic/Latina women: findings from the Sister Study.

BACKGROUND: Poor sleep is associated with increased hypertension risk, but few studies have evaluated multiple sleep dimensions or investigated racial/ethnic disparities in this association among women. METHOD: We investigated multiple sleep dimensions (sleep duration, inconsistent weekly sleep patterns, sleep debt, frequent napping and difficulty falling or staying asleep) and hypertension risk among women, and determined modification by age, race/ethnicity and menopausal status. We used data from the Sister Study, a national cohort of 50 884 women who had sisters diagnosed with breast cancer in the United States enrolled in 2003-2009 and followed through September 2018. RESULTS: Of 33 497 women without diagnosed hypertension at baseline (mean age ±â€Šstandard deviation: 53.9 ±â€Š8.8 years; 88.7% White, 6.4% Black and 4.9% Hispanic/Latina), 23% (n = 7686) developed hypertension over a median follow-up of 10.1 years [interquartile range: 8.2-11.9 years]. Very short, short or long sleep duration, inconsistent weekly sleep patterns, sleep debt, frequent napping, insomnia, insomnia symptoms as well as short sleep and exploratory cumulative poor sleep score were associated with incident hypertension after adjustment for demographics factors. After additional adjustment for lifestyle and clinical factors, insomnia [hazard ratio = 1.09, 95% confidence interval (95% CI): 1.03-1.15] and insomnia symptoms plus short sleep (hazard ratio = 1.13, 95% CI: 1.05-1.21) remained associated with incident hypertension. These associations were stronger in younger (age<54 vs. ≥54 years) and premenopausal vs. postmenopausal women (all P-interaction < 0.05). Associations did not differ by race/ethnicity (all P-interaction > 0.05). CONCLUSION: Thus, screening for multiple sleep dimensions and prioritizing younger and premenopausal women may help identify individuals at high risk for hypertension.

Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial Differences in Stroke Study.

Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.

Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial.

OBJECTIVE: To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. METHODS: We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed. RESULTS: Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events. CONCLUSION: Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.

Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided.

Cardiovascular Health and Transition From Controlled Blood Pressure to Apparent Treatment Resistant Hypertension: The Jackson Heart Study and the REGARDS Study.

Almost 1 in 5 US adults with hypertension has apparent treatment resistant hypertension (aTRH). Identifying modifiable risk factors for incident aTRH may guide interventions to reduce the need for additional antihypertensive medication. We evaluated the association between cardiovascular health and incident aTRH among participants with hypertension and controlled blood pressure (BP) at baseline in the Jackson Heart Study (N=800) and the Reasons for Geographic and Racial Differences in Stroke study (N=2316). Body mass index, smoking, physical activity, diet, BP, cholesterol and glucose, categorized as ideal, intermediate, or poor according to the American Heart Association's Life's Simple 7 were assessed at baseline and used to define cardiovascular health. Incident aTRH was defined by uncontrolled BP, systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg, while taking ≥3 classes of antihypertensive medication or controlled BP, systolic BP <130 mm Hg and diastolic BP <80 mm Hg, while taking ≥4 classes of antihypertensive medication at a follow-up visit. Over a median 9 years of follow-up, 605 (19.4%) participants developed aTRH. Incident aTRH developed among 25.8%, 18.2%, and 15.7% of participants with 0 to 1, 2, and 3 to 5 ideal Life's Simple 7 components, respectively. No participants had 6 or 7 ideal Life's Simple 7 components at baseline. The multivariable adjusted hazard ratios (95% CIs) for incident aTRH associated with 2 and 3 to 5 versus 0 to 1 ideal components were 0.75 (0.61-0.92) and 0.67 (0.54-0.82), respectively. These findings suggest optimizing cardiovascular health may reduce the pill burden and high cardiovascular risk associated with aTRH among individuals with hypertension.

Underutilization of Treatment for Black Adults With Apparent Treatment-Resistant Hypertension: JHS and the REGARDS Study.

Resistant hypertension, defined as blood pressure levels above goal while taking ≥3 classes of antihypertensive medication or ≥4 classes regardless of blood pressure level, is associated with increased cardiovascular disease risk. The 2018 American Heart Association Scientific Statement on Resistant Hypertension recommends healthy lifestyle habits and thiazide-like diuretics and mineralocorticoid receptor antagonists for adults with resistant hypertension. The term apparent treatment-resistant hypertension (aTRH) is used when pseudoresistance cannot be excluded. We estimated the use of healthy lifestyle factors and recommended antihypertensive medication classes among US Black adults with aTRH. Data were pooled for Black participants in the JHS (Jackson Heart Study) in 2009 to 2013 (n=2496) and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) in 2013 to 2016 (n=3786). Outcomes included lifestyle factors (not smoking, not consuming alcohol, ≥75 minutes of vigorous-intensity or ≥150 minutes of moderate or vigorous physical activity per week, and body mass index <25 kg/m2) and recommended antihypertensive medications (thiazide-like diuretics and mineralocorticoid receptor antagonists). Overall, 28.3% of participants who reported taking antihypertensive medication had aTRH. Among participants with aTRH, 14.5% and 1.2% had ideal levels of 3 and 4 of the lifestyle factors, respectively. Also, 5.9% of participants with aTRH reported taking a thiazide-like diuretic, and 9.8% reported taking a mineralocorticoid receptor antagonist. In conclusion, evidence-based lifestyle factors and recommended pharmacological treatment are underutilized in Black adults with aTRH. Increased use of lifestyle recommendations and antihypertensive medication classes specifically recommended for aTRH may improve blood pressure control and reduce cardiovascular disease-related morbidity and mortality among US Black adults. Graphic Abstract A graphic abstract is available for this article.

Life's Simple 7 and Incident Hypertension: The REGARDS Study.

Background The Life's Simple 7 (LS7) metric incorporates health behaviors (body mass index, diet, smoking, physical activity) and health factors (blood pressure, cholesterol, glucose) to estimate an individual's level of cardiovascular health. The association between cardiovascular health and incident hypertension is unresolved. Hypertension's threshold was recently lowered and it is unclear if better cardiovascular health is associated with lower risk of incident hypertension with the updated threshold or in a multirace cohort. We sought to assess the association between better LS7 score and risk of incident hypertension among Black and White adults using a 130/80 mm Hg hypertension threshold. Methods and Results We determined the association between LS7 metric and incident hypertension in the REGARDS (Reasons for Geographic and Racial Disparities in Stroke) study, including participants free of baseline hypertension (2003-2007) who completed a second visit between 2013 and 2016. Hypertension was defined as systolic/diastolic blood pressure ≥130/80 mm Hg or antihypertensive medication use. Each LS7 component was assigned 0 (poor), 1 (intermediate), or 2 (ideal) points. We generated a 14-point score by summing points. Among 2930 normotensive participants (20% Black, 80% White), the median (25th-75th percentiles) LS7 total score was 9 (8-10) points. Over a median follow-up of 9 years, 42% developed hypertension. In the fully adjusted model, each 1-point higher LS7 score had a 6% lower risk of incident hypertension (risk ratio, 0.94 per 1 point; 95% CI, 0.92-0.96). Conclusions Better cardiovascular health was associated with lower risk of incident hypertension using a 130/80 mm Hg hypertension threshold among Black and White adults.

Association of Sustained Blood Pressure Control with Multimorbidity Progression Among Older Adults.

BACKGROUND/OBJECTIVES: Due to the high costs and excess mortality associated with multimorbidity, there is a need to develop approaches for delaying its progression. High blood pressure (BP) is a common chronic condition and a risk factor for many additional chronic conditions, making it an ideal target for intervention. The purpose of this analysis was to determine the association between the level of sustained BP control and the progression of multimorbidity. DESIGN: Retrospective cohort study. SETTING: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims. PARTICIPANTS: A total of 6,591 ALLHAT participants with Medicare who had systolic BP (SBP) measurements at eight or more study visits. MEASUREMENTS: SBP control was categorized as lower than 140 mm Hg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Multimorbidity progression was defined by the number of incident chronic conditions, including arthritis, asthma, atrial fibrillation, cancer, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, dementia, depression, diabetes mellitus, heart failure, hyperlipidemia, osteoporosis, and stroke. Recurrent event survival analysis was used to calculate rate ratios (RRs) for the association of sustained SBP control with progression of multimorbidity. RESULTS: Rates of incident conditions per 10 person-years (95% CIs) were 5.2 (5.1-5.4), 4.7 (4.5-4.8), 4.4 (4.2-4.5), and 4.0 (3.8-4.2) for participants with SBP control at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively, over a median follow-up of 9.0 years. Compared with participants with SBP control at less than 50% of visits, adjusted RRs (95% CIs) for multimorbidity progression were 0.90 (0.86-0.95), 0.85 (0.81-0.89), and 0.77 (0.72-0.82) for those with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively. CONCLUSIONS: Sustaining BP control may be an effective approach to slow multimorbidity progression and may reduce the population burden of multimorbidity.