Incidence of Atherosclerotic Cardiovascular Disease in Young Adults at Low Short-Term But High Long-Term Risk.

BACKGROUND: Young adults may have high long-term atherosclerotic cardiovascular disease (ASCVD) risk despite low short-term risk. OBJECTIVES: In this study, we sought to compare the performance of short-term and long-term ASCVD risk prediction tools in young adults and evaluate ASCVD incidence associated with predicted short-term and long-term risk. METHODS: We included adults aged 18 to 39 years, from 2008 to 2009 in a U.S. integrated health care system, and followed them through 2019. We calculated 10-year and 30-year ASCVD predicted risk and assessed ASCVD incidence. RESULTS: Among 414,260 young adults, 813 had an incident ASCVD event during a median of 4 years (maximum 11 years). Compared with 10-year predicted risk, 30-year predicted risk improved reclassification (net reclassification index: 16%) despite having similar discrimination (Harrell's C: 0.749 vs 0.726). Overall, 1.0% and 2.2% of young adults were categorized as having elevated 10-year (≥7.5%) and elevated 30-year (≥20%) predicted risk, respectively, and 1.6% as having low 10-year (<7.5%) but elevated 30-year predicted risk. The ASCVD incidence rate per 1,000 person-years was 2.60 (95% CI: 1.92-3.52) for those with elevated 10-year predicted risk, 1.87 (95% CI: 1.42-2.46) for those with low 10-year but elevated 30-year predicted risk, and 0.32 (95% CI: 0.30-0.35) for those with low 10-year and 30-year predicted risk. The age- and sex-adjusted incidence rate ratio was 3.04 (95% CI: 2.25-4.10) comparing those with low 10-year but elevated 30-year predicted risk and those with low 10-year and 30-year predicted risk. CONCLUSIONS: Long-term ASCVD risk prediction tools further discriminate a subgroup of young adults with elevated observed risk despite low estimated short-term risk.

Treatment of Hypertension: A Review.

Importance: Hypertension, defined as persistent systolic blood pressure (SBP) at least 130 mm Hg or diastolic BP (DBP) at least 80 mm Hg, affects approximately 116 million adults in the US and more than 1 billion adults worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (coronary heart disease, heart failure, and stroke) and death. Observations: First-line therapy for hypertension is lifestyle modification, including weight loss, healthy dietary pattern that includes low sodium and high potassium intake, physical activity, and moderation or elimination of alcohol consumption. The BP-lowering effects of individual lifestyle components are partially additive and enhance the efficacy of pharmacologic therapy. The decision to initiate antihypertensive medication should be based on the level of BP and the presence of high atherosclerotic CVD risk. First-line drug therapy for hypertension consists of a thiazide or thiazidelike diuretic such as hydrochlorothiazide or chlorthalidone, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker such as enalapril or candesartan, and a calcium channel blocker such as amlodipine and should be titrated according to office and home SBP/DBP levels to achieve in most people an SBP/DBP target (<130/80 mm Hg for adults <65 years and SBP <130 mm Hg in adults ≥65 years). Randomized clinical trials have established the efficacy of BP lowering to reduce the risk of CVD morbidity and mortality. An SBP reduction of 10 mm Hg decreases risk of CVD events by approximately 20% to 30%. Despite the benefits of BP control, only 44% of US adults with hypertension have their SBP/DBP controlled to less than 140/90 mm Hg. Conclusions and Relevance: Hypertension affects approximately 116 million adults in the US and more than 1 billion adults worldwide and is a leading cause of CVD morbidity and mortality. First-line therapy for hypertension is lifestyle modification, consisting of weight loss, dietary sodium reduction and potassium supplementation, healthy dietary pattern, physical activity, and limited alcohol consumption. When drug therapy is required, first-line therapies are thiazide or thiazidelike diuretics, angiotensin-converting enzyme inhibitor or angiotensin receptor blockers, and calcium channel blockers.

Dyskalemia risk associated with fixed-dose anti-hypertensive medication combinations.

A model-based meta-analysis quantified comparative dyskalemia risk (hyper- or hypo-kalemia) in hypertensive patients treated with angiotensin receptor blockers (ARBs), a calcium channel blocker (CCB) and/or a thiazide diuretic (hydrochlorothiazide; HCTZ) as monotherapy or as fixed-dose combinations. Among 15 randomized controlled trials in a US Food and Drug Administration regulatory review database, dyskalemia events were reported by five trials (24 treatment arms, 11,030 subjects, 8-week median follow up time). The five trials evaluated monotherapy (ARB or HCTZ) alongside dual (ARB + HCTZ, ARB + CCB, or HCTZ + CCB) or triple fixed-dose combinations (ARB + CCB + HCTZ). Hypo- and hyper-kalemia rates were analyzed jointly to account for correlation. Significant drug class, drug, or dose effects were included in the final model. Effect on various drug- and dose combinations on dyskalemia risk were simulated and compared with model-estimated placebo arm dyskalemia risk. After a typical follow-up of 8 weeks, fixed-dose combinations of ARB with a high dose (25 mg) of HCTZ were associated with a higher hypokalemia risk difference (RD) from placebo (e.g.,Valsartan + HCTZ: 2.52%[95%CIs:1.17, 4.38%]). However, when ARB was combined with a lower, 12.5 mg dose of HCTZ, hypokalemia RD from placebo was not significant (Valsartan + HCTZ: -0.03%[-0.80, 0.71%]). ARB monotherapy raised hyperkalemia RD from placebo (1.3%[0.3, 3.6%]). Hyperkalemia risk was not appreciably higher than placebo for any FDC that combined ARB with HCTZ (Valsartan + HCTZ: 0.06%[-1.48, 1.64%]). In uncomplicated hypertensive patients, ARB + 12.5 mg HCTZ fixed-dose combinations are safer with respect to dyskalemia than either ARB or HCTZ monotherapy for initial antihypertensive treatment.

Treatment Patterns and Blood Pressure Control With Initiation of Combination Versus Monotherapy Antihypertensive Regimens.

Many patients with hypertension require 2 or more drug classes to achieve their blood pressure (BP) goal. We compared antihypertensive medication treatment patterns and BP control between patients who initiated combination therapy versus monotherapy. We identified adults with hypertension enrolled in a US integrated healthcare system who initiated antihypertensive medication between 2008 and 2014. Patient demographics, clinical characteristics, antihypertensive medication, and BP were extracted from electronic health records. Antihypertensive medication patterns and multivariable adjusted prevalence ratios (PRs) of achieving the 2017 American College of Cardiology/American Heart Association guideline-recommended BP <130/80 mm Hg were evaluated for 2 years following treatment initiation. Of 135 971 patients, 43% initiated antihypertensive combination therapy (35% ACE [angiotensin converting enzyme] inhibitor (ACEI)-thiazide diuretics; 8% with other combinations) and 57% initiated monotherapy (22% ACEIs; 16% thiazide diuretics; 11% ß blockers; 8% calcium channel blockers). After multivariable adjustment including premedication BP levels, patients who initiated ACEI-thiazide diuretic combination therapy were more likely to achieve BP <130/80 mm Hg compared with their counterparts who initiated monotherapy with ACEI (PR, 1.10 [95% CI, 1.08-1.12]), thiazide diuretic (PR, 1.21 [95% CI, 1.18-1.24]), ß blocker (PR, 1.17 [95% CI, 1.14-1.20]), or calcium channel blocker (PR, 1.25 [95% CI, 1.22-1.29]). Compared with initiating monotherapy, patients initiating ACEI-thiazide diuretic combination therapy were more likely to achieve BP goals.

Recurrent Atherosclerotic Cardiovascular Event Rates Differ Among Patients Meeting the Very High Risk Definition According to Age, Sex, Race/Ethnicity, and Socioeconomic Status.

Background The risk for atherosclerotic cardiovascular disease (ASCVD) events may differ by sociodemographic factors among patients meeting the definition of very high risk according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline, leading to treatment disparities. We estimated the risk for recurrent ASCVD events among adults meeting the definition of very high risk by age, sex, race/ethnicity, and socioeconomic status in a US integrated healthcare system. Methods and Results The study cohort included Kaiser Permanente Southern California members aged ≥21 years with a history of clinical ASCVD on September 30, 2009. Very high risk for recurrent ASCVD was defined by a history of ≥2 major ASCVD events or a history of 1 major event along with ≥2 high-risk conditions. Patients were followed through 2015 for a first recurrent ASCVD event. Of 77 101 patients with ASCVD, 50.8% met the definition for very high risk. Among patients meeting the definition of very high risk, recurrent ASCVD rates were higher in older (>75 years) versus younger patients (21-40 years) (sex-adjusted hazard ratio [HR] [95% CI] 1.85; 1.23-2.79), non-Hispanic Black patients versus non-Hispanic White patients (age-, sex-adjusted HR, 1.32; 1.23-1.41), those who lived in neighborhoods with lower (<$35k) versus higher annual household income (≥$80k) (HR, 1.20; 1.11-1.30), or with lower (≥31.2%) versus higher education levels (<8.8% high school or lower) (HR, 1.26; 1.19-1.34). Conclusions Disparities in the risk for recurrent ASCVD events were present across sociodemographic factors among very high risk patients. The addition of sociodemographic factors to current definitions of very high risk could reduce health disparities.

Trends in Antihypertensive Medication Monotherapy and Combination Use Among US Adults, National Health and Nutrition Examination Survey 2005-2016.

Blood pressure (BP) control rates among US adults taking antihypertensive medication have not increased over the past decade. Many adults require 2 or more classes of antihypertensive medication to achieve guideline-recommended BP goals, but the proportion of US adults taking antihypertensive medication monotherapy, versus combination therapy, has not been quantified using contemporary data. We analyzed data from 2005 to 2008, 2009 to 2012, and 2013 to 2016 National Health and Nutrition Examination Surveys to determine trends in monotherapy and combinations of antihypertensive medication classes among US adults age ≥20 years with hypertension taking antihypertensive medication (n=7837). The proportion of US adults taking antihypertensive medication with uncontrolled BP (ie, systolic BP ≥140 or diastolic BP ≥90 mm Hg) was 32.3%, 30.2%, and 31.0% in 2005 to 2008, 2009 to 2012, and 2013 to 2016, respectively (Ptrend=0.37). Between 2005 to 2008 and 2013 to 2016, there was no evidence of changes in the proportions of US adults taking antihypertensive monotherapy (39.5%-40.4%, Ptrend=0.67), dual-therapy (37.9%-38.3%, Ptrend=0.75), triple-therapy (17.6%-16.5%, Ptrend=0.36), or quadruple-therapy (4.4%-4.3%, Ptrend=0.93). Between 2005 to 2008 and 2013 to 2016, there was no evidence of changes in the proportions of US adults with uncontrolled BP taking antihypertensive monotherapy (39.3%-40.6%, Ptrend=0.78). A high proportion of US adults with hypertension, including those with uncontrolled BP, are taking one antihypertensive medication class. Increasing the use of dual- and triple-therapy antihypertensive medication regimens may restore the upward trend in BP control rates among US adults.

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey).

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mm Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min-1·1.73 m-2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. RESULTS: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. CONCLUSIONS: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.