Lawrence J Appel

Johns Hopkins Medicine | JHUSOM

Serum urate is a risk factor for hypertension and gout. The DASH diet and losartan independently lower blood pressure (BP); however, their effects on serum urate are understudied. We performed a post-hoc analysis of the DASH-losartan trial, which randomized participants with hypertension in parallel fashion to the DASH diet or a standard American d...

Background: There is inconsistent evidence on the optimal time after standing to assess for orthostatic hypotension. We determined the prevalence of orthostatic hypotension at different time points after standing in a population of older adults, as well as fall risk and symptoms associated with orthostatic hypotension. Methods: We performed a se...

Rational & objective: Uromodulin (UMOD) is the most abundant protein found in urine and has emerged as a promising biomarker of tubule health. Circulating UMOD is also detectable, but at lower levels. We evaluated whether serum UMOD levels were associated with risk of incident kidney failure with replacement therapy (KFRT) and mortality. Study de...

Importance: Clinical practice guidelines recommend selecting an appropriately sized cuff based on mid-arm circumference prior to measuring blood pressure (BP). To our knowledge, the effect of miscuffing on BP measurement when using an automated BP device has not been quantified. Objective: To determine the effect of using a regular BP cuff vs an...

Objectives Team-based care is essential for improving hypertension outcomes in low-resource settings. We assessed perceptions of country representatives and healthcare workers (HCWs) on team-based hypertension care in low/middle-income countries. Design Two cross-sectional surveys. Setting The first survey (Country Profile Survey) was conducted i...

The growing burden of hypertension (HT) is projected to reach 1.56 billion globally by 2025 and is an increasing public health concern, even for low- and middle-income countries (LMIC) like Uganda, where the prevalence of HT is 31.5%. The objective of this study was to test the effectiveness of a freely available HT online course on knowledge compe...

Background: Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not. Objective: To determine whether AKI is independently associated with subsequent kidney function traject...

Background Within healthy dietary patterns, manipulation of the proportion of macronutrient can reduce CVD risk. However, the biological pathways underlying healthy diet-disease associations are poorly understood. Using an untargeted, large-scale proteomic profiling, we aimed to (1) identify proteins mediating the association between healthy dietar...

Importance: Tobacco smoking drives markedly elevated cardiovascular disease risk and preventable death in persons with serious mental illness, and these risks are compounded by the high prevalence of overweight/obesity that smoking cessation can exacerbate. Guideline-concordant combined pharmacotherapy and behavioral smoking cessation treatment im...

BACKGROUND The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feed...

Rationale and objective: Hypertension is a known risk factor for dementia and cognitive impairment. There are limited data on the relation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with incident cognitive impairment in adults with chronic kidney disease. We sought to identify and characterize the relationship among blood...

The efficacy of time-restricted eating for weight loss has not been established, as prior studies were limited by a lack of controlled isocaloric designs. This study describes the design and implementation of interventions in a controlled eating study evaluating time-restricted eating. We designed a randomized, controlled, parallel-arm eating study...

Children delivered by elective, prelabor Cesarean section (C-section) are not exposed to the birth canal microbiota and, in relation to vaginally delivered children, show altered microbiota development. Perturbed microbial colonization during critical early-life windows of development alters metabolic and immune programming and is associated with a...

SARS-CoV-2 antibody levels associated with reduced hospitalization risk remain undefined. Our outpatient COVID-19 convalescent plasma (CCP), placebo-controlled trial observed SARS-CoV-2 antibody levels decreasing 22-fold from matched donor units into post-transfusion seronegative recipients. Unvaccinated recipients were jointly stratified by a) ear...

Rationale & objective: Ultraprocessed foods are widely consumed in the US and are associated with cardiovascular disease (CVD), mortality, and kidney function decline in the general population. We investigated associations between ultraprocessed food intake and chronic kidney disease (CKD) progression, all-cause mortality, and incident CVD in adul...

Background The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results Large‐s...

Rationale & objective: The heart-kidney crosstalk is recognized as the cardiorenal syndrome. We examined the association of cardiac function and structure with the risk of kidney failure with replacement therapy (KFRT) in a chronic kidney disease (CKD) population. Study design: Prospective observational cohort study. Setting & participants: 3,...

Background: While prior studies demonstrated that a low-sodium, DASH diet reduced blood pressure, the effects of sodium reduction, alone or in combination with the DASH diet, on kidney function are still unknown. Objective: We measured cystatin C in stored specimens of the DASH-Na trial, to determine the effects of sodium reduction and the DASH die...

Introduction: A team-based care approach to hypertension care in low-resource settings is an effective strategy for improving hypertension control. Objective: In this multi-country survey, we assessed the extent to which team-based care is operationalized for hypertension care in low- and middle-income countries (LMICs), and the perception of hyper...

Background: Clinical trials for weight loss in cancer survivors have been shown to be safe and effective. Pragmatic approaches are needed to facilitate broader adoption. The ASPIRE study evaluates real-world, lifestyle weight loss programs in Maryland on reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) outcomes. Here we repo...

Background: In observational studies, older adults with insufficient or deficient serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation. This is possibly because the doses of vitamin D supplements tested were too low. Objective...

Introduction: Noncommunicable diseases (e.g. type 2 diabetes, hypertension, cardiovascular disease) are the leading cause of death globally and among adults in Ethiopia. Suboptimal diet (with high intake of sugar, salt, and saturated fat) is a major risk factor for such diseases and the consumption of processed foods rich in these nutrients is risi...

Introduction: Orthostatic hypotension (OH) is prevalent in older adults and associated with poor health outcomes. Physical activity (PA) may attenuate the risk of OH, but evidence of the association between daily volume and patterns of objectively measured PA and OH is lacking. Hypothesis: Lower daily volume and higher fragmentation of PA are assoc...

Introduction: Albuminuria, an early marker of kidney damage, is a risk factor for chronic kidney disease (CKD) progression, cardiovascular disease (CVD), and death. Dietary sodium is a risk factor for elevated blood pressure, CVD, and all cause-mortality. It is particularly important in patients with CKD due to increased salt-sensitivity. It is unc...

Introduction: The Dietary Approaches to Stop Hypertension (DASH) diet significantly reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. Hypothesis: We hypothesized that certain metabolites will be associated with BP reductions. Methods: Metabolomic profiling was conducted at the end of the diet...

Introduction: Salivary amylase, encoded by the AMY1 gene, plays a pivotal role in carbohydrate digestion, and genetic adaptation of carbohydrate digestion has been implicated in impaired glucose tolerance, type 2 diabetes, and cardiometabolic diseases. Hypothesis: We investigated whether AMY1 genetic variations are associated with β-cell function a...

Background: Both the glycemic index (GI) and amounts of carbohydrates are important determinants of postprandial glucose changes. Recent studies suggest the effects of carbohydrate intake on postprandial glucose metabolism may differ according to meal timing, showing circadian patterns. Hypothesis: We investigated whether the relations of altering...

Background: To assess whether vitamin D3 supplementation attenuates the decline in daily physical activity in low-functioning adults at risk for falls. Methods: Secondary data analyses of STURDY (Study to Understand Fall Reduction and Vitamin D in You), a response-adaptive randomized clinical trial. Participants included 571 adults aged 70 years...

Background The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to reduce biomarkers of cardiovascular disease. We aimed to characterize the time course of change in biomarkers of cardiac injury (high‐sensitivity cardiac troponin I), cardiac strain (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]), and inflammation (hs‐CRP [...

Although modern risk estimators, such as the American College of Cardiology/American Heart Association Pooled Cohort Equation, play a central role in the decisions of patients to start pharmacologic therapy to prevent atherosclerotic cardiovascular disease (ASCVD), there is limited evidence to inform expectations for 10-year ASCVD risk reduction fr...

In order to achieve population-wide control of hypertension, team-based care is essential, especially in low- and middle-income countries (LMIC) where there are insufficient numbers of physicians to diagnose hypertension and prescribe medications. RTSL is a global initiative to dramatically improve hypertension control from 14% to 50% worldwide. On...

To evaluate the effectiveness and safety of a community health worker intervention for diagnosing and managing hypertension (HTN) in rural Nepal. We conducted a quasi-experimental study in two rural municipalities in Nepal, assigning one as an active site (7 communities) and the other as a comparison site (8 communities, which received enhanced usu...

Reforms to scale up hypertension treatment are needed in India, where < 20% of individuals with hypertension have controlled blood pressure. Limited medication supply and short prescription periods are two key barriers to increase hypertension treatment coverage in the public health system. We estimated the benefits on medication coverage of three...

Background The worldwide control rate for hypertension is dismal. An inadequate number of physicians to treat patients with hypertension is one key obstacle. Innovative health system approaches such as delegation of basic tasks to non-physician health workers (task-sharing) might alleviate this problem. Massive scale up of population-wide hypertens...

Background Arterial calcification and stiffness are common in people with chronic kidney disease (CKD).Higher vitamin K status has been associated with less arterial calcification and stiffness in CKD in cross-sectional studies Objective To determine the association of vitamin K status with coronary artery calcium (CAC) and arterial stiffness (pul...

Background: Risk factors for high blood pressure (BP) in children start in utero . Cord blood metabolites reflect exposures of the developing fetus to the in utero environment. No studies have examined whether cord blood metabolites are associated with BP in children. Objectives: To examine prospective associations of cord blood metabolites with sy...

Introduction: Branched-chain amino acids (BCAAs), i.e., leucine, isoleucine, and valine, are involved in glucose regulation, immunity, and cell signaling. Higher circulating BCAAs were associated with incident cardiovascular disease (CVD) in the general population which may be mediated by insulin resistance. BCAA’s role in CVD in the absence of dia...

Introduction: Chronic kidney disease (CKD) is associated with arrhythmias such as atrial fibrillation (AF) and sudden cardiac death, but limited rigorous data exist on the prevalence of AF, ventricular tachycardia (VT), nonsustained VT (NSVT), and high-degree atrioventricular (AV) block in a CKD cohort. Hypothesis: In participants with CKD, worse k...

This letter comments on the letter by Baker et al.

Importance Low-carbohydrate diets decrease hemoglobin A 1c (HbA 1c ) among patients with type 2 diabetes at least as much as low-fat diets. However, evidence on the effects of low-carbohydrate diets on HbA 1c among individuals with HbA 1c in the range of prediabetes to diabetes not treated by diabetes medications is limited. Objective To study the...

Rationale and Objective Chronic Kidney Disease is a risk-enhancing factor for cardiovascular disease (CVD) and mortality and the role of aspirin use is unclear in this population. We investigated the risk and benefits of aspirin use in primary and secondary prevention of CVD in the Chronic Renal Insufficiency Cohort (CRIC) Study. Study Design Pros...

The purpose of this paper is to evaluate the quality of information and guidance on dietary sodium reduction available on consumer-facing websites. Google Trends was used to identify the five most-used search terms related to dietary sodium reduction. For each term, websites on the first two pages were collected (n = 18-20). Of 93 websites collecte...

Background Limited data exist on the benefits of lifestyle behavior change delivered using telehealth and web‐based applications with varied support on blood pressure (BP). Methods and Results We conducted a 2‐site randomized controlled trial at Geisinger (January 2019–March 2021) to compare the efficacy of 2 remotely delivered strategies using we...

Introduction: Low physical activity is a criterion of phenotypic frailty defined as an increased state of vulnerability to adverse health outcomes. Whether disengagement from daily all-purpose physical activity is prospectively associated with frailty, and possibly modified by chronic inflammation-a pathway often underlying frailty-remains unexplo...

Background: No studies have examined whether the cord blood metabolome-a reflection of in utero metabolism-influences blood pressure (BP) in children. Objectives: To examine prospective associations of cord blood metabolites with systolic BP (SBP), diastolic BP (DBP), and risk of elevated BP in children. Methods: In the Boston Birth Cohort, we...

Background Differences in death rate and cardiovascular disease (CVD) between Black and White patients with chronic kidney disease is attributed to sociocultural factors, comorbidities, genetics, and inflammation. Methods and Results We examined the interaction of race, plasma IL‐6 (interleukin‐6), and TMPRSS6 genotype as determinants of CVD and m...

The efficacy of time-restricted feeding for weight loss has not been established as prior studies were limited by lack of controlled isocaloric designs. This study describes the design and implementation of a controlled feeding study evaluating time-restricted feeding. We designed a randomized, controlled, parallel-arm, feeding study comparing time...

Background: Salt substitution (ie, replacement of table and cooking salt with potassium-enriched salt substitutes) is a promising strategy to reduce blood pressure and prevent cardiovascular disease, particularly in countries like India where there is high sodium intake, mainly from discretionary salt, and low potassium intake. Life-threatening hy...

Background and objectives Mitochondrial DNA copy number is a biomarker of mitochondrial function, which has been hypothesized to contribute to pathogenesis of CKD through podocyte injury, tubular epithelial cell damage, and endothelial dysfunction. The prospective association of mitochondrial DNA copy number with CKD progression has not been previo...

Background Short chain fatty acids (SCFAs) are microbially derived end products of dietary fiber fermentation. The SCFA butyrate reduces blood pressure (BP) in mouse models. The association of SCFAs, including butyrate, with BP in humans is unclear, due in part to predominantly cross‐sectional analyses and different biospecimens (blood versus fecal...

Purpose In pre-planned observational analysis of the POWER-remote trial, we examined the impact of weight loss on patient-reported outcomes (PROs). We hypothesized a priori that survivors with ≥ 5% weight loss would have improved physical function (PF) at 6 months vs. those who did not. Methods Patients with stage 0-III breast cancer who completed...

Purpose of Review The scientific consensus on which global health organizations base public health policies is that high sodium intake increases blood pressure (BP) in a linear fashion contributing to cardiovascular disease (CVD). A moderate reduction in sodium intake to 2000 mg per day helps ensure that BP remains at a healthy level to reduce the...

Background: Low-carbohydrate diets decrease hemoglobin A1c among patients with type 2 diabetes mellitus. However, evidence on effects of low-carbohydrate diets on hemoglobin A1c among individuals with prediabetes is limited. Methods: We conducted a randomized parallel-group trial of 150 adults aged 40-70 years with untreated hemoglobin A1c from 6.0...

Introduction This study aimed to document the long-term effects on beverage sales of a 6-year intervention campaign to reduce consumption of sugar-sweetened beverages (SSBs). Methods In 2013, a multi-component intervention campaign designed to reduce intake of sugary drinks was launched in Howard County, MD (HC). A difference-in-differences regres...

Abstract Background Inadequate adherence to hypertension (HT) clinical standards by healthcare providers is one of the major barriers for HT management. We examined the effectiveness of four short instructional training videos on HT management. Methods Eighteen primary health care facilities were randomly selected using systematic sampling from fiv...

Adherence is critical in feeding studies to determine the efficacy of dietary interventions. This time-restricted intake of meals (TRIM) investigation was a controlled feeding study that randomized 41 participants to follow 12 weeks of time-restricted feeding (TRF) or a usual feeding pattern (UFP). Adherence was optimized through careful screening...

Background Contemporary guidelines recommend using atherosclerotic cardiovascular disease screening tools to guide primary prevention. The performance of these scores is not well known in patients with moderate to advanced chronic kidney disease, particularly in combination with clinically available cardiac biomarkers including N‐terminal pro–brain...

Background Chronic kidney disease (CKD) is associated with anxiety and depression. Although the coronavirus disease 2019 (COVID-19) pandemic has increased stressors on patients with CKD, assessments of anxiety and its predictors and consequences on behaviors, specifically virus mitigation behaviors, are lacking. Methods From June to October 2020,...

Context The Study To Understand Fall Reduction and Vitamin D in You (STURDY), a randomized trial enrolling older adults with low 25-hydroxyvitamin D [25(OH)D], demonstrated vitamin D supplementation ≥1000 IU/day did not prevent falls compared to 200 IU/day, with doses ≥2000 IU/day potentially showing safety concerns. Objective To examine associati...

Background Low serum 25-hydroxyvitamin D [25(OH)D] level is associated with a greater risk of frailty, but the effects of daily vitamin D supplementation on frailty are uncertain. This secondary analysis aimed to examine the effects of vitamin D supplementation on frailty using data from the Study To Understand Fall Reduction and Vitamin D in You (...

Introduction Lifestyle behavior modification interventions, delivered using telehealth, have been shown to be effective in reducing weight. However, limited data exists on the benefits of lifestyle behavior change delivered using telehealth and web-based applications on blood pressure (BP). Methods We conducted a 2-site randomized controlled trial...

Background: Orthostatic hypotension (OH) based on a change from seated-to-standing blood pressure (BP) is often used interchangeably with supine-to-standing BP. Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a randomized trial of vitamin D3 supplementation and fall in adults aged ≥70 years at high risk of falls...

Background: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. Methods: In this multicenter, double-blind, randomized, controlled trial, we evaluated the effi...

Background Deoxycholic acid (DCA) is a secondary bile acid that may promote vascular calcification in experimental settings. Higher DCA levels were associated with prevalent coronary artery calcification (CAC) in a small group of individuals with advanced chronic kidney disease. Whether DCA levels are associated with CAC prevalence, incidence, and...

Background: Higher baseline levels of soluble TNF receptors (TNFR1 and TNFR2) have been associated with progressive CKD. Whether longitudinal changes in these biomarkers of inflammation are also associated with worse kidney outcomes has been less studied. Methods: We evaluated associations of longitudinal changes in TNFR1 and TNFR2 with ESKD in...

Background Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet enhances potassium intake and reduces sodium intake and blood pressure (BP), but the underlying metabolic pathways are unclear. Objective Among free-living populations, delineate metabolic signatures associated with the DASH diet adherence, 24-hr urinary sodium and pot...

Background/objectives Lipopolysaccharide-binding protein (LBP), a biomarker of gut barrier permeability to lipopolysaccharides, is higher in adults with obesity and type 2 diabetes. Behavioral weight loss and metformin have distinct effects on the gut microbiome, but their impact on gut permeability to lipopolysaccharides is unknown. This study’s o...

Introduction: Overweight and obesity in youth with serious emotional disturbance (SED) is exceedingly common. In 2015 the AHA called attention to mental illnesses in youth as important risk conditions for early CVD and the need for transformational change in management of overweight and obesity in this group. Our objective was to test a 12-month, i...

Objective: To evaluate the quality of information and guidance on dietary sodium reduction available on consumer-facing websites. Methods: Google Trends was used to identify the five most used search terms related to sodium reduction. For each term, the top 20 websites were collected. Of 93 unique websites, 69 met inclusion criteria. Each website w...

Introduction: Hypertension is the leading cause of morbidity and mortality in low- and middle-income countries (LMICs). However, data on the prevalence of hypertension in rural areas are limited. Aim: To characterize the prevalence of hypertension in rural areas of Nepal. Methods: Data were collected from two rural municipalities (Rupa and Biruwa)...

Introduction: Telehealth and web-based applications are increasingly available to promote healthy lifestyle behavior change. However, evidence that these approaches lower blood pressure is limited. Methods: We conducted a randomized controlled trial to compare the efficacy of a self-directed vs. a telehealth-delivered dietitian approach using web-b...

Background: Blood pressure (BP) guidelines recommend individualized cuff selection based on mid-arm circumference, but many clinics, especially in resource-constrained settings, use a regular adult cuff for all patients. Objective: Determine the effects of using a regular adult BP cuff compared to using a BP cuff that is appropriately sized for an...

Background: Short chain fatty acids (SCFAs) are the microbially-derived end products of dietary fiber fermentation. The SCFA butyrate is a signaling molecule shown to influence blood pressure (BP) in mouse models. The association of butyrate and other SCFAs on BP in humans is unclear, due in part to predominantly cross-sectional analyses and to dif...

Background: A bidirectional relationship between cardiovascular disease and chronic kidney disease (CKD) is well-recognized, but the association of cardiac dysfunction and structure with the risk of CKD progression has not been systematically evaluated in a CKD population. Methods: We analyzed Chronic Renal Insufficiency Cohort participants who und...