Flowchart of the search.

<p>Flowchart of the search.</p

Pre-set inclusion and exclusion criteria.

<p>Pre-set inclusion and exclusion criteria.</p

Flowchart of the search.

<p>Flowchart of the search.</p

Critical appraisal of animal studies.

<p><b>Study aim</b>:+: study is focused on interpreting the relation between sympathetic activity (SNA) and diastolic dysfunction (DD); -: study is not focused on interpreting the relation between SNA and DD. <b>Clearly defined hypothesis</b>: +: hypothesis clearly defined; +/-: aim of study clearly defined, no hypothesis formulated; -: no clear aim nor hypothesis. <b>Model to induce HFPEF</b>: +: ISO infusion; -: transaortic constriction. <b>Assessment of diastolic dysfunction</b>: +: invasive measurement of LV diastolic filling pressures or echocardiographic evaluation of DD according to latest ESC guidelines; +/-: echocardiographic evaluation without use of E/E’; -: confirmation of normal LVEF only. <b>Assessment of sympathetic activity</b>: +: yes; +/-: no. <b>Clear report of findings</b>: +: results clearly described AND critical about own research; +/-: results clearly described OR critical about own research; -: results not clearly described AND not critical about own research. <b>Value of study</b>: To what extent is the study relevant to answering the current question.</p><p>The score displayed in the right column is the sum of scores: “+” accounts for 1 point; “+/-” for 0 points; “-” for -1 point.</p><p>Critical appraisal of animal studies.</p

Critical appraisal of human studies.

<p><b>Number of patients</b> = : Number of patients with diastolic dysfunction/HFPEF. <b>Study aim</b>: ++: study is focused on interpreting the relation between SNA and DD <b>AND</b> patient selection was clearly explained (diastolic dysfunction defined and not just distinction between LVEF 45%) <b>AND</b> data collection was clear. +: study is focused on interpreting the relation between SNA and DD <b>AND</b> patient selection was clearly explained <b>OR</b> data collection was clear; -: study is focused on interpreting the relation between SNA and DD <b>OR</b> patient selection was clearly explained <b>OR</b> data collection was clear; —: study is not focused on interpreting the relation between SNA and DD <b>AND/OR</b> patient selection was not clearly explained <b>AND/OR</b> data collection was not clear. <b>Patient selection</b>: +: Sole HFPEF or clear distinction between HFPEF and HFREF; -: no clear distinction between HFPEF and HFREF. <b>Assessment of diastolic dysfunction</b>: +: invasive measurement of LV diastolic filling pressures OR echocardiographic evaluation of DD according to latest ESC guidelines; +/-: echocardiographic evaluation without use of E/E’; -: confirmation of normal LVEF only. <b>Evaluation of sympathetic activity</b>: ++: NE-spillover locally measured; +: MSNA OR MIBG; +/-: HRV or adrenergic stimulation; -: plasma NE concentration. <b>Clear report of findings</b>: +: results clearly described AND critical about own research; +/-: results clearly described OR critical about own research; -: results not clearly described AND not critical about own research. <b>Value of study</b>: To what extent is the study relevant to answering the current question.</p><p>The score displayed in the right column is the sum of scores: “+” accounts for 1 point; “+/-” for 0 points; “-” for -1 point.</p><p>Critical appraisal of human studies.</p

ROC curves of model 1, A, consisting of symptoms.

<p>The black line describes the diagnostic value in men and the red line the diagnostic value in women. The AUC in women is not inferior to the AUC in men, p-value 0.45. ROC curves of model 2, B, consisting of symptoms added with baseline characteristics. The black line describes the diagnostic value in men and the red line in women. The AUC in women is not inferior to the AUC in men, p-value 0.11.</p

Flowchart.

<p>Flowchart.</p

Association (OR +95% CI) between symptoms/cardiovascular risk factors and CAD in women and men as estimated by multivariable logistic regression analysis (model 2).

<p>Only variables from the univariable analysis with a p-value < 0.15 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116431#pone.0116431.t001" target="_blank">table 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116431#pone.0116431.t002" target="_blank">2</a>) were included in the multivariable analysis). AUC (area under the curve) was calculated using variables with a p-value <0.15 from the multivariable analysis. The presence of symptoms with a negative predictive value was associated with not having CAD.</p><p>Association (OR +95% CI) between symptoms/cardiovascular risk factors and CAD in women and men as estimated by multivariable logistic regression analysis (model 2).</p

Association (OR +95% CI) between symptoms and CAD in women and men as estimated by multivariable logistic regression analysis (model 1).

<p>Only variables from the univariable analysis with a p-value < 0.15 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116431#pone.0116431.t001" target="_blank">table 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116431#pone.0116431.t002" target="_blank">2</a>) were included in the multivariable analysis. AUC (area under the curve) was calculated using variables with a p-value <0.15 from the multivariable analysis. The presence of symptoms with a negative predictive value was associated with not having CAD.</p><p>Association (OR +95% CI) between symptoms and CAD in women and men as estimated by multivariable logistic regression analysis (model 1).</p

Univariable analysis (odds ratios) of all symptoms in women and men separately.

<p>Univariable analysis (odds ratios) of all symptoms in women and men separately.</p