Sundar Natarajan

Cholesterol measures to identify and treat individuals at risk for coronary heart disease

BACKGROUND Low-density lipoprotein (LDL)-based guidelines are currently used to initiate and monitor cholesterol-lowering therapy. METHODS Using stratified analyses, data from the Framingham Heart Study and the Coronary Primary Prevention Trial were evaluated to determine whether (1) cholesterol levels (total cholesterol [TC] or LDL [low-density lipoprotein]) better discriminated risk for coronary heart disease (CHD) than cholesterol ratios (LDL/HDL [high-density lipoprotein] or TC/HDL); and (2) whether changes in ratios better predicted risk reduction than changes in levels. RESULTS Individuals with similar LDL/HDL ratios had similar risks for CHD regardless of whether they had high LDL levels or low LDL levels (23% vs 23% for the CPPT, 13.8% vs 14% for FHS men, and 8.6% vs 10.9% for FHS women). Among men with similar initial LDL/HDL ratios and similar changes in LDL/HDL ratios, risks for CHD did not differ (20.3% compared with 21.0%; p =0.96) between those with the largest and smallest reductions in LDL levels (21.3% compared with 6.5%). Among men with similar initial LDL levels and similar LDL reductions, a 20% reduction in risk for CHD was seen (19.5% compared with 24.5%; p =0.005) between those with the largest and smallest reductions in LDL/HDL ratios (23% compared with 4.6%). TC/HDL had predictive ability similar to LDL/HDL. CONCLUSIONS Cholesterol levels do not provide incremental predictive value over cholesterol ratios in identifying people at risk for CHD. Changes in ratios are better predictors of successful CHD risk reduction than changes in levels. Future guidelines should consider incorporating ratios in initiating and monitoring successful lipid-lowering therapy.

Association Between a DASH-Like Diet and Mortality in Adults With Hypertension: Findings From a Population-Based Follow-Up Study

BACKGROUND Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP) in hypertensive adults, its effect on mortality is unclear. METHODS This prospective cohort study evaluated the association between diet and mortality in 5,532 hypertensive adults in the Third National Health and Nutrition Examination Survey. Hypertension was determined by self-report, medication use, or BP measurement. Diet was ascertained by 24-h dietary recall using nine nutrient targets. The primary outcome was all-cause mortality. Secondary outcomes included specific causes of mortality (cardiovascular disease (CVD), ischemic heart disease (IHD), stroke, and cancer). RESULTS Of the 5,532 participants, 391 (7.1%) consumed a DASH-like diet. During an average of 8.2 person-years of follow-up, there were 1,537 all-cause deaths; this included 312 cancer deaths and 788 cardiovascular deaths, of which 447 were due to IHD and 142 were due to stroke. After adjusting for multiple confounders while accounting for the complex survey design by utilizing survey weights, strata, and clusters in Cox proportional hazards models, a DASH-like diet was associated with lower mortality from all causes (hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.52-0.92, P = 0.01) and stroke (HR 0.11, 95% CI 0.03-0.47, P = 0.003). Mortality risk from CVD (HR 0.92, 95% CI 0.63-1.35, P = 0.67), IHD (HR 0.77, 95% CI 0.47-1.24, P = 0.28), and cancer (HR 0.51, 95% CI 0.23-1.10, P = 0.09) did not reach statistical significance. CONCLUSIONS Though findings for specific causes of mortality are mixed, consumption of a DASH-like diet is associated with lower all-cause mortality in adults with hypertension.

Iron deficiency in community-dwelling US adults with self-reported heart failure in the National Health and Nutrition Examination Survey III: prevalence and associations with anemia and inflammation.

Background— Iron deficiency has been proposed as a potential therapeutic target in heart failure, but its prevalence and association with anemia and clinical outcomes in community-dwelling adults with heart failure have not been well characterized. Methods and Results— Using data from the Third National Health and Nutrition Examination Survey, we evaluated the associations between iron deficiency, hemoglobin, C-reactive protein (CRP), and all-cause and cardiovascular mortality in 574 adults with self-reported heart failure. Iron deficiency was defined in both absolute and functional terms as a ferritin level <100 &mgr;g/L or between 100 and 299 &mgr;g/L if the transferrin saturation was <20%. Iron deficiency was present in 61.3% of participants and was associated with reduced mean hemoglobin (13.6 versus 14.2 g/dL, P=0.007) and increased mean CRP (0.95 versus 0.63 mg/dL, P=0.04). Over a median of 6.7 years of follow-up, there were 300 all-cause deaths, 193 of which were from cardiovascular causes. In age- and sex-adjusted Cox proportional hazards models, hemoglobin, CRP, and transferrin saturation but not iron deficiency were significantly associated with all-cause and cardiovascular mortality. In multivariate models, hemoglobin remained an independent predictor of cardiovascular mortality, whereas CRP remained an independent predictor of both all-cause and cardiovascular mortality. Conclusions— Iron deficiency is common in heart failure and is associated with decreased hemoglobin and increased CRP. In multivariate analysis, hemoglobin was associated with cardiovascular mortality while CRP was associated with both all-cause and cardiovascular mortality. Iron deficiency was not associated with all-cause or cardiovascular mortality in this cohort.

Self-Report of High Cholesterol Determinants of Validity in U.S. Adults

BACKGROUND Hypercholesterolemia is a major cardiovascular risk factor, and cholesterol awareness is important in both clinical practice and in public health. We evaluated the validity of self-reported hypercholesterolemia and identified determinants of validity. METHODS The study design was a cross-sectional survey, from 1988 to 1994, of adult participants (N=8236) from the Third National Health and Nutrition Examination Survey for whom self-report of hypercholesterolemia and serum measurement were available. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for self-reported hypercholesterolemia were calculated using total cholesterol > or =5.17 mmol/L (200 mg/dL) and/or taking cholesterol-lowering medication as the criterion standard. RESULTS Overall test characteristics for self-report were sensitivity, 51%; specificity, 89%; PPV, 87%; and NPV, 55%. Sensitivity of self-report was higher among older subjects and non-Hispanic whites, specificity was higher among subjects with >12 years of education, PPV was higher in older subjects, and NPV was higher in younger subjects and in those with >12 years of education. Using higher cholesterol thresholds to define hypercholesterolemia led to higher sensitivity, lower specificity, lower PPV, and higher NPV. Sociodemographic and anthropometric predictors of validity were identified by logistic regression. CONCLUSIONS Due to low sensitivity, self-reported hypercholesterolemia should be used with caution, both during the patient encounter and for surveillance of trends in hypercholesterolemia in the absence of measured cholesterol levels. Specificity is consistently much higher than sensitivity. The high PPV may be of use in certain clinical situations. Such validation studies should form the foundation for future research based on self-report.

Iron Deficiency in Community-Dwelling US Adults With Self-Reported Heart Failure in the National Health and Nutrition Examination Survey IIIClinical Perspective

Background— Iron deficiency has been proposed as a potential therapeutic target in heart failure, but its prevalence and association with anemia and clinical outcomes in community-dwelling adults with heart failure have not been well characterized. Methods and Results— Using data from the Third National Health and Nutrition Examination Survey, we evaluated the associations between iron deficiency, hemoglobin, C-reactive protein (CRP), and all-cause and cardiovascular mortality in 574 adults with self-reported heart failure. Iron deficiency was defined in both absolute and functional terms as a ferritin level <100 &mgr;g/L or between 100 and 299 &mgr;g/L if the transferrin saturation was <20%. Iron deficiency was present in 61.3% of participants and was associated with reduced mean hemoglobin (13.6 versus 14.2 g/dL, P=0.007) and increased mean CRP (0.95 versus 0.63 mg/dL, P=0.04). Over a median of 6.7 years of follow-up, there were 300 all-cause deaths, 193 of which were from cardiovascular causes. In age- and sex-adjusted Cox proportional hazards models, hemoglobin, CRP, and transferrin saturation but not iron deficiency were significantly associated with all-cause and cardiovascular mortality. In multivariate models, hemoglobin remained an independent predictor of cardiovascular mortality, whereas CRP remained an independent predictor of both all-cause and cardiovascular mortality. Conclusions— Iron deficiency is common in heart failure and is associated with decreased hemoglobin and increased CRP. In multivariate analysis, hemoglobin was associated with cardiovascular mortality while CRP was associated with both all-cause and cardiovascular mortality. Iron deficiency was not associated with all-cause or cardiovascular mortality in this cohort.

Usefulness of a run-in period to reduce drop-outs in a randomized controlled trial of a behavioral intervention

OBJECTIVES We evaluated the usefulness of a simple run-in period to reduce drop-outs in a behavioral intervention to improve blood pressure (BP). In a pilot study where a run-in period was not used, we had a 25% drop-out rate. METHODS A prospective evaluation was performed in the context of a blinded 3-arm randomized trial. Participants are eligible if they have uncontrolled BP on 2 consecutive visits. Potential participants are approached during a routine visit, informed, consented and enrolled. After a 1-month run-in period during which all participants receive a phone call to: i) verify phone availability, ii) get basic information on treatment, and iii) confirm the baseline visit, participants return for a baseline visit. They are then randomized to one of the three treatment arms: usual care, non-tailored counseling, or tailored counseling. Participants make return visits at 3, 6 and 12 months. RESULTS Of the 1275 potential participants who received detailed study information, 301 consented to participate, of whom 226 were enrolled. During the run-in period, 73 withdrew consent and 153 participants were randomized; 7 subsequently dropped out. There were no differences (p>.1) between the 73 cancelled and the 153 randomized patients. There were fewer drop-outs than in the pilot study (5% vs. 25%, p<.0001). CONCLUSIONS The run-in period reduces the number of drop-outs after randomization and improves statistical power. In order to retain external validity, it is important to compare participants who remain in the study and those that cancel, and incorporate that in generalizing from the study.

Effect of Treatment and Adherence on Ethnic Differences in Blood Pressure Control Among Adults with Hypertension

We evaluated whether hypertension control differs by ethnicity after accounting for patient characteristics, treatment, and adherence to treatment using the third National Health and Nutrition Examination Survey (US population estimate, 42,511,379). Outcome measures were prescribed treatment, treatment adherence, hypertension control (blood pressure [BP]<140/90 mm Hg). Multivariate logistic regression was performed with non-Hispanic whites (NHW) as the comparison group. Non-Hispanic blacks (NHB) were more likely to report medication prescription (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.5) and being advised to restrict salt (OR 1.5, CI: 1.2-2.0). Among those advised, NHB were more likely to report salt restriction (OR 1.5, CI: 1.1-2.1) and weight-loss attempts (OR 1.7, CI: 1.3-2.3). Among persons advised to follow exercise, alcohol restriction, smoking cessation, tension reduction, or diet modification, NHB (OR 2.2, CI: 1.6-3.0) and Mexican Americans (OR 2.0, CI: 1.1-3.9) were more likely to report adherence. The likelihood of uncontrolled hypertension was higher in NHB (OR 1.4, CI: 1.1-1.7) and Mexican Americans (OR 1.5, CI 1.1-2.0) despite medication adherence. Even after adjustment for treatment and adherence, substantial ethnic differences in hypertension control were found. Initiating treatment, while crucial, is not sufficient and future guidelines should emphasize aggressive treatment escalation to achieve hypertension control.

Effectiveness of a Tailored Behavioral Intervention to Improve Hypertension Control Primary Outcomes of a Randomized Controlled Trial

&NA;Blood pressure (BP) control rates are suboptimal. We evaluated the effectiveness of 2 behavioral interventions to improve BP control via a 3-arm, randomized controlled trial of 533 adults with repeated uncontrolled BP, despite antihypertensive drug treatment for ≥6 months. The interventions were a tailored stage-matched intervention (SMI) or a nontailored health education intervention (HEI) of 6 monthly calls targeting diet, exercise, and medication. Control was usual care (UC). There were no baseline group differences. Baseline BP control was 42.6%, 40.6%, and 44.6% in SMI, HEI, and UC (P=0.74), respectively; systolic BP (with SEs) was 136 (0.89), 137 (1.33), and 137 (0.96) mm Hg. Six-month control was 64.6% (SMI), 54.3% (HEI), and 45.8% (UC) (P values for pairwise comparisons versus UC, 0.001 [SMI] and 0.108 [HEI]). At 6 months, systolic BP (SE) was 131.2 (1.05), 131.8 (0.99), and 134.7 (1.02) for SMI, HEI, and UC, respectively (P values for pairwise comparisons versus UC, 0.009 for SMI and 0.047 for HEI). SMI led to lower systolic BP and better BP control than UC. SMI constitutes a new, potent approach to assist patients with uncontrolled hypertension to reach BP goals. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00286754.Blood pressure (BP) control rates are suboptimal. We evaluated the effectiveness of 2 behavioral interventions to improve BP control via a 3-arm, randomized controlled trial of 533 adults with repeated uncontrolled BP, despite antihypertensive drug treatment for ≥6 months. The interventions were a tailored stage-matched intervention (SMI) or a nontailored health education intervention (HEI) of 6 monthly calls targeting diet, exercise, and medication. Control was usual care (UC). There were no baseline group differences. Baseline BP control was 42.6%, 40.6%, and 44.6% in SMI, HEI, and UC ( P =0.74), respectively; systolic BP (with SEs) was 136 (0.89), 137 (1.33), and 137 (0.96) mm Hg. Six-month control was 64.6% (SMI), 54.3% (HEI), and 45.8% (UC) ( P values for pairwise comparisons versus UC, 0.001 [SMI] and 0.108 [HEI]). At 6 months, systolic BP (SE) was 131.2 (1.05), 131.8 (0.99), and 134.7 (1.02) for SMI, HEI, and UC, respectively ( P values for pairwise comparisons versus UC, 0.009 for SMI and 0.047 for HEI). SMI led to lower systolic BP and better BP control than UC. SMI constitutes a new, potent approach to assist patients with uncontrolled hypertension to reach BP goals. Clinical Trial Registration— URL: . Unique identifier: [NCT00286754][1]. # Novelty and Significance {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00286754&atom=%2Fhypertensionaha%2F65%2F2%2F440.atom

The Mobile Insulin Titration Intervention (MITI) for Insulin Adjustment in an Urban, Low-Income Population: Randomized Controlled Trial

Background Diabetes patients are usually started on a low dose of insulin and their dose is adjusted or “titrated” according to their blood glucose levels. Insulin titration administered through face-to-face visits with a clinician can be time consuming and logistically burdensome for patients, especially those of low socioeconomic status (SES). Given the wide use of mobile phones among this population, there is the potential to use short message service (SMS) text messaging and phone calls to perform insulin titration remotely. Objective The goals of this pilot study were to (1) evaluate if our Mobile Insulin Titration Intervention (MITI) intervention using text messaging and phone calls was effective in helping patients reach their optimal insulin glargine dose within 12 weeks, (2) assess the feasibility of the intervention within our clinic setting and patient population, (3) collect data on the cost savings associated with the intervention, and (4) measure patient satisfaction with the intervention. Methods This was a pilot study evaluating an intervention for patients requiring insulin glargine titration in the outpatient medical clinic of Bellevue Hospital Center in New York City. Patients in the intervention arm received weekday SMS text messages from a health management platform requesting their fasting blood glucose values. The clinic’s diabetes nurse educator monitored the texted responses on the platform website each weekday for alarm values. Once a week, the nurse reviewed the glucose values, consulted the MITI titration algorithm, and called patients to adjust their insulin dose. Patients in the usual care arm continued to receive their standard clinic care for insulin titration. The primary outcome was whether a patient reached his/her optimal insulin glargine dose within 12 weeks. Results A total of 61 patients consented and were randomized into the study. A significantly greater proportion of patients in the intervention arm reached their optimal insulin glargine dose than patients in the usual care arm (88%, 29/33 vs 37%, 10/27; P<.001). Patients responded to 84.3% (420/498) of the SMS text messages requesting their blood glucose values. The nurse reached patients within 2 attempts or by voicemail 91% of the time (90/99 assigned calls). When patients traveled to the clinic, they spent a median of 45 minutes (IQR 30-60) on travel and 39 minutes (IQR 30-64) waiting prior to appointments. A total of 61% (37/61) of patients had appointment copays. After participating in the study, patients in the intervention arm reported higher treatment satisfaction than those in the usual care arm. Conclusions MITI is an effective way to help low-SES patients reach their optimal insulin glargine dose using basic SMS text messaging and phone calls. The intervention was feasible and patients were highly satisfied with their treatment. The intervention was cost saving in terms of time for patients, who were able to have their insulin titrated without multiple clinic appointments. Similar interventions should be explored to improve care for low-SES patients managing chronic disease. Trial Registration Clinicaltrials.gov NCT01879579; https://clinicaltrials.gov/ct2/show/NCT01879579 (Archived by WebCite at http://www.webcitation.org/6YZik33L3).

Challenges and recommendations for blinding in behavioral interventions illustrated using a case study of a behavioral intervention to lower blood pressure

OBJECTIVE To describe the challenges to blinding in behavioral interventions, specifically those for asymptomatic medical conditions, where the intervention is through counseling, and to provide recommendations for achieving blinding in behavioral randomized controlled trials (RCTs). METHODS This paper reviews the challenges of preserving blinding in behavioral RCTs with a focus on interventions for asymptomatic medical conditions. This is illustrated using a case study of an ongoing behavioral intervention to improve hypertension control. RESULTS In contrast to easily keeping study investigators and participants masked to treatment assignment through the use of identical pills or sham treatments, the need to have differing levels of blinding among study personnel and participants in randomized behavioral intervention trials is presented. Recommendations for achieving this are provided. CONCLUSIONS Despite the challenges inherent in behavioral interventions, it is possible to achieve differing levels of blinding across study personnel and participants to minimize bias and generate valid data in RCTs that test interventions for asymptomatic medical conditions such as hypertension. Modifications may be needed for RCTs in symptomatic medical conditions. PRACTICE IMPLICATIONS Researchers designing behavioral RCTs should be aware of the challenges to blinding all staff and study participants, and plan to have procedures in place to standardize outcome data collection and intervention delivery without compromising the varying levels of blinding. The challenges and recommendations described may need modifications in behavioral intervention studies for symptomatic conditions.